■rrr -' ' ■ * E PHYSiOi [muscular BAlISi^ St^aca, S^ttt) lath BOUGHT WITH THE INCOME OF THE SAGE ENDOWMENT FUND THE GIFT OF HENRY W. SAGE IStl Cornell University Library The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924003152943 MONOGRAPHS ON PHYSIOLOGY EDITED BY ERNEST H.. STARLING, M.D., D.Sc, F.R.S., F.R.C.P. MONOGRAPHS ON PHYSIOLOGY EDITED BY ERNEST H. STARLING, M.D., D.Sc, F.R.S., F.R.C.P. 8vo. THE INVOLUNTARY NERVOUS SYSTEM. By WALTER HoLEKOOK Gaskell, M.A., M.D., F.R.S. With 9 Diagrams. 7J. net. THE SECRETION OF THE URINE. By Arthur R. Cushny, M.A. , M. D. , F.R.S. , Professor of Materia Medica and Pharmacology in the University of Edinburgh. With Diagrams. 9;. 6d. net. THE CONDUCTION OF THE NERVOUS IMPULSE. By Keith Lucas, M.A., ScD., F.R.S. Revised by E. D. Adrian, M.B., M.R.C.P., Fellow of Trinity College, Cambridge. With Diagrams. 5^. net. THE PHYSIOLOGY OF MUSCULAR EXERCISE. By F. A. Bainbridge, M.A., M.D., D.Sc., F.R.C.P., F.R.S., Professor of Physiology in the University of London. With 22 Diagrams, los, bd. net. LONGMANS, GREEN AND CO. LONDON, NEW YORK, BOMBAY, CALCUTTA, AND MADRAS THE PHYSIOLOGY OF MUSCULAR EXERCISE BY F. A. BAINBRIDGE M.A., M.D. CANTAB., D.Sc, F.R.C.P., F.R.S. PROFESSOR OF PHYSIOLOGY, UNIVERSITY OF LONDON WITH 22 DIAGRAMS LONGMANS, GREEN AND CO. 39 PATERNOSTER ROW, LONDON .FOURTH AVENyE & 30th STREET, NEW YORK BOMBAY, CALCUTTA, AND MADRAS I9I9 A 45-^^1 ^2:^ "The strength of the British Empire lies in the strength of character of the individual Englishman, taken all alone by himself. And that strength I am per- suaded is perennially nourished and kept up by nothing so much as by the national worship, in which all classes meet, of athletic outdoor life and sport." — William James. EDITOR'S PREFACE. In no science is the advance at any one time general. Some sections of the line are pushed forward while other parts may remain for years with little movement, until in their turn they are enabled to progress in consequence of the support afforded by the advance of the adjacent sections. The increasing n umber of series of monographs in different sciences is a recognition of this fact, as well as of the concentration of interest which characterises this age of specialisation. In the present series it is intended to set out the progress of physiology in those chapters in which the forward movement is the most pronounced. Each mono- graph will contain an account of our knowledge of some particular branch of physiology, written by one who has himself contributed in greater or less degree to the attain- ment of our present position. It is hoped that by securing the help of men who are actively engaged in the advance of the subject the outlook of each monograph will be for- wards rather than backwards. An exhaustive account of previous writings on the subject concerned is not aimed at, but rather an appreciation of what is worth retaining in past work, so far as this is suggestive of the paths along which future research may be fruitful of results. The more valuable the monographs in inspiring the work of others, the greater will be the success of the series. ERNEST H. STARLING. AUTHOR'S PREFACE. Rigid investigation of the nature and significance of the processes taking place in the body during muscular exercise must, .a^ a rule, be undertaken in the laboratory. It is, however, those in charge of patients, or responsible for the health and training of large groups of individuals, who are brought into direct contact with the problems presented by exercise, as carried out under the ordinary conditions of daily life. The fullest co-operation between the laboratory worker and the physician is of supreme importance for bringing about a clearer understanding and more effective practical application of the principles underlying the behaviour of the body during muscular exercise, since on a knowledge of these principles depends success or failure in the treatment of the unfit and in the building up of the sound man. In writing this monograph, therefore, I have attempted to present my subject in such a way as to promote a closer connection between the investigator in the laboratory and those directly concerned with the health and well-being of the community. CONTENTS. PAGE Editor's Preface v Author's Preface vii CHAP. I. Introductory .......... i II. The Sources of Muscular Energy— The Mechanical Efficiency of the Body — The Temperature of the Body during Exercise . 5 •• III. The Respiratory Changes during Exercise— The Reaction of the Blood during Exercise 23 IV. The Output of the Heart during Exercise— The Diastolic Filling of the Heart— The Output per Beat— The Size of the Heart during Exercise ........ 43 V. The Output of the Heart {continued)— The: Influence of the Pulse-rate upon the Output of the Heart— The Behaviour of the Heart during Exercise — The Mechanical Efficiency of the Heart 64 VI. The Blood-supply to the Active Organs during Exercise — The Arterial Pressure 84 VII. The Passage of Oxygen into the Tissues during Exercise — The Consumption of Oxygen by the Muscles — The Consumption of Oxygen by the Heart 100 VIII. The Co-ordination of the Changes Occurring during Exercise — The Initial Co-ordinating Mechanisms — Later Co-ordinat- ing Mechanisms — Exercise under Emotional Stress — The Limits of Muscular Exertion 115 IX. Training — The General Effects of Training — Exercise in the Trained and Untrained Man — Second Wind . . • 1 39 X. Exercise at High Altitudes — The Process of Acclimatisation — The Passage of Oxygen into the Blood — The Changes during Exercise ... . . . . . .151 XI. The After-effects of Exercise — Circulatory and Respiratory Changes — Fatigue — Beneficial Effects of Exercise . ■ 171 XII. The After-effects of Exercise {continued) — Effort-Syndrome — Over-stress of the Heart 187 Bibliography ........... 203 Index 215 ix CHAPTER I. INTRODUCTORY. Muscular exercise is of such constant occurrence in daily life,' and its more obvious effects are so familiar to every one, that the complexity of the processes underlying it is apt to be overlooked. Yet a knowledge of the changes taking place in the body during exercise, and of the adjustments involved in carrying it out effi- ciently, is of more than mere academic interest. It is essential, for example, that the clinician, who is called upon almost daily to decide whether, and to what extent, his patients should take exer- cise, should be acquainted with the effects which muscular activity produces upon the various organs of the body, and particularly with the significance of the circulatory and respiratory changes associated with it. Further, the elaborate investigations of in- dustrial fatigue which have been carried out during the last few years leave no doubt that not only the efficiency of the worker as a member of the community, but also his health, and even his entire outlook upon life, are closely bound up with the con- ditions under which his manual labour is carried out. A fuller realisation and a more direct practical application, by employers and administrators, of the physiological principles, which underlie the capacity of the body to perform muscular work, would un- doubtedly greatly increase the output and improve the health of industrial workers. Muscular exercise is the highest expression of the activities of the body considered merely as a machine, and almost all the resources of the body are mobilised in order to bring about the greatest efficiency of the neuro-muscular system. To a spectator its most conspicuous features are the wonderful co-ordination of the muscular movements and the immense power of the body to develop energy, particularly when these are displayed to perfec- tion, as, for example, in the gracefulness of an expert dancer or I 2 THE PHYSIOLOGY OF MUSCULAR EXERCISE figure-skater, or in the power of a trained crew rowing in a boat- race. These are rendered possible by the concentration for the time being of the entire energies of the higher nervous centres upon the actual muscular movement, and the individual, who is engaged in such exercise, is usually conscious of little but the effort he is making, his whole attention being focussed upon the actual physical exertion. The important part played by the central nervous system is also seen in the large accession of working power which occurs, when exercise is performed under the stimulating influence of emotional excitement, or, conversely, in the lessened efficiency' of a man who is not interested in the work which he is carrying out. Since muscular exercise is as much a nervous as a muscular pro- cess, its beneficial effects are evident in the psychical as well as the physical life of the individual ; and, as William James has said: "Even if the day ever dawns in which it will not be needed for fighting the old heavy battles against nature, it (muscular vigour) will still always be needed to furnish the background of sanity. Serenity, and cheerfulness to life, to give moral elasticity to our disposition, to round off the wiry edge of our fretfulness, and make us good-humoured and easy of approach". Consequently, induced movements — useful though they may be — fall far short of voluntary exercise as a means of maintaining health and vigour. Although the nervous system initiates and controls every movement of the body, the energy required for the carrying out of physical work is developed in the muscles themselves, and their power to transform potential into kinetic energy, which appears as work or heat, and to renew their store of energy is the central fact of muscular exercise. For a long time, physi- ologists were content. to study the causes of this transformation of energy and the conditions which regulate the mechanical efficiency of the muscles. Their investigations, carried out for the most part on isolated muscle, yielded many valuable results, but the tendency to regard muscular exercise as almost exclu- sively a muscular act led to a narrow and imperfect conception of its true character. It has gradually become clear, however, that the processes taking place in the muscles, important though they are, constitute only a fraction of the total activities of the body during exercise, and that muscular movement is a very INTRODUCTORY 3 different thing from voluntary exercise. Although the setting free of energy, when a muscle contracts, is a non-oxidative pro- cess, oxygen is necessary for the restoration of its potential energy, and, in the absence of oxygen, mammalian muscle rapidly loses the power of contraction. Further, since the energy of muscular work is ultimately obtained from the oxida- tion of the food-stuffs, the enormous increase in the amount of energy developed in the muscles during exercise involves a corresponding rise in the intensity of their metabolic activities and in the extent to which they consume oxygen. Indeed, it is now well known that the amount of oxygen which a man con- sumes is a criterion of the degree of activity of his muscles during exercise. A man, who is performing hard physical work, may use eight or ten times as much oxygen as during rest, and the burden •of meeting this demand for oxygen falls upon the respiratory and circulatory systems, which, for this purpose, are indissolubly linked together. Every increase in the requirements of the body for oxygen is accompanied by adaptive changes in the circulation and the respiration, which enable oxygen to be transferred more rapidly from the lungs to the tissues ; and the rapid, deep breath- ing, the powerfully beating heart, the high blood-pressure, and the frequent pulse, present in the man who is engaged in violent exercise, are just as much a part of the exercise, and just as vital to its effective performance, as the movements of the muscles themselves. Violent exercise taxes the resources of the circulatory and respiratory systems equally with those of the muscles ; and, partly because it is called upon to maintain an adequate supply of oxygen to the brain as well as to the muscles, partly, perhaps, owing to the larger number and greater com- plexity of the adjustments required for this purpose, the heart, as a rule, reaches the limit of its powers earlier than the skeletal muscles, and its functional capacity determines a man's capability for exertion. It is clear, then, that, apart from the changes taking place in the muscles themselves, the activities of the rest of the body are largely directed during exercise to the provision of an adequate supply of oxygen for the muscles, the heart, and the brain ; hence any picture of muscular exercise must include the whole range of these activities. If the body is to work efficiently and to develop its physical 4 THE PHYSIOLOGY OF MUSCULAR EXERCISE powers to their full extent, it is absolutely essential that the movements of the muscles on the one hand, and the activities of the circulatory and respiratory systems on the other hand, should be co-ordinated and integrated into a harmonious whole. Perfect co-ordination brings about the maximum of work with the minimum of effort. Incomplete co-ordination, on the contrary, inevitably spells inefficiency. An exaggerated response on the part of the respiratory and circulatory systems involves a useless expenditure of energy ; a deficient response rapidly throws out of gear the controlling influence of the nervous system, cripples the energies of the skeletal muscles, and renders exercise ineffec- tive or even impossible. In order to realise the completeness to which this co-ordination can attain, and the eifects of even the slightest disturbance of the balance between the activities of the muscles and of the rest of the body, it is only necessary to watch a trained and an untrained man running in a race or engaged in some other form of exercise. In the former, every organ is working smoothly, and is contributing its proper share towards ^bringing about the perfect harmony of action which is requisite for efficient exercise. In the latter, the less perfect adjustment of the body is evident, both to the man himself and to others, in the greater sense of effort, in the clumsiness of movement, and in the more severe respiratory and circulatory distress. Muscular exercise thus presents three problems. The first is the changes taking place in the skeletal muscles, whereby the transformation of energy, which constitutes muscular movement, is effected ; the second is the nature of the adjustments occurring elsewhere in the body in order to provide the muscles with the oxygen and food-stuffs required for this purpose ; and the third is the means by which these are interwoven and bound together to produce the fabric of muscular exercise. The attempt to answer the second and third of these questions is the main thesis of the following chapters, and the first question will only be con- sidered in so far as it bears upon the general argument. CHAPTER II. THE SOURCES OF MUSCULAR ENERGY— THE MECHANICAL EFFI- CIENCY OF THE BODY— THE TEMPERATURE OF THE BODY DURING EXERCISE. From a metabolic point of view the immense development of energy which takes place in the body during heavy work is the most striking feature of muscular exercise. Thus, Benedict and Cathcart (1913) found that, in one subject, the total production of energy, which varied from 1-09 to i'27 calories per minute during absolute rest, reached from 10 to 14 calories per minute during heavy work. In one experiment, carried out on a bicycle ergometer, the subject — a professional cyclist — performed in a little over four hours an amount of work, which was equivalent to a cycle ride of I GO miles ; throughout this period his produc- tion of energy averaged 975 calories per minute. This figure is probably not far short of the maximal production of energy of which the body is capable for a prolonged period of work, although a considerably larger output of energy per minute is possible during a brief spell of very severe work, such as running upstairs with a heavy load. The two questions which naturally spring from observations of this kind are, first, from what source do the muscles obtain the potential energy which they transform into kinetic energy, and, second, what fraction of the total energy produced in the active ■ muscles is converted into effective, external work ? Underlying these questions is a further problem, namely, what is the real nature of the processes of which a muscular contrac- tion is the outward manifestation ? No detailed discussion of these questions is possible here, but it is necessary to refer briefly to two aspects of the metabolism during exercise, namely, the sources of muscular energy and the mechanical eflficiency of the body. 6 'THE PHYSIOLOGY OF MUSCULAR EXERCISE The Sources of Muscular Energy. The belief that protein normally' serves directly as a source of muscular energy has long been abandoned. The greater excretion of uric acid (Cathcart, Kennaway, and Leathes, 1908, Kennaway, 1908), and of creatinin (Leathes and Orr, 191 2), in the urine after severe physical exertion represents merely a greater wear and tear of the muscle ; and the trivial extent of the increase indicates that, as regards its chemical structure, the muscular machine is remarkably stable. The energy, which the muscular machine transforms into external work, must therefore be provided by the oxidation either of fat or carbohydrate or of both these substances. Xhe Respiratory Quotient. The problem as to the nature of the material oxidised during muscular work was first seriously attacked by Chauveau (1896), who studied the effect of muscular exercise upon the respiratory quotient. He observed that the respiratory quotient rose consider- ably during exercise, although it tended to fall again if the exercise was prolonged. He regarded the initial rise in the respiratory quotient as evidence that carbohydrate is the sole source of muscular energy, and the subsequent fall of the quotient as in- dicating the conversion of fat into carbohydrate as a preliminary to its final oxidation. Chauveau's conclusions were vigorously controverted by Zuntz (1896), who found that the respiratory quotient was unaffected hy exercise, whether the diet was rich in carbohydrate and poor in fat, or rich in fat and poor in carbo- hydrate ; and his observations accord with those of Loewy (1908), of Katzenstein (1891), and of others. The following table is taken from Katzenstein, the observations being made on man : — TABLE I. Oxygen Intake C.C. per Minute. CO, Output C.C. per Minute. Respiratory Quotient. Rest .... Walking on level ground . Climbing .... 2637 763-0 I2S2'2 2II-0 6142 IO02'5 o-8o o-8o o-8o On the ground lof these observations, Zuntz put forward the view that the muscles, whether resting or active, utilise fat and _ THE SOURCES OF MUSCULAR ENERGY 7 carbohydrate in the proportions in which they are presented to the muscles. Additional support for this view was found both in the fact that vigorous muscular work can be carried out by a starving man, whose store of carbohydrate has presumably almost disappeared, and also in observations, such as those of Atwater and Benedict (1903), and of Zuntz (1900), on the amount and efficiency of the work performed on a diet rich or poor in carbo- hydrate. Zuntz found in one experiment that the performance of I kilogrammetre of work involved the production of 9-3 calories of heat (above the resting value) on a carbohydrate diet, and of 10-3 calories on a diet consisting chiefly of fat; thus the work was carried out almost equally efficiently whatever the character of the diet. » This observation was confirmed by Atwater and Benedict who found, as the following figures show, that the total produc- tion of heat during the performance of a given amount of mechanical work was the same, whether the diet was rich or poor in carbohydrate : — TABLE II. « Fat Diet. Carbohydrate Diet. Mechanical work (calculated as heat)' . Heat production Total expenditure of energy . 55° 4555 5105 543 4593 5136 These experiments do not prove conclusively that fat can be utilised as a source of muscular energy, since, at least in Atwater and Benedict's observations, sufficient carbohydrate was available in the body to provide the energy expended. They do appear to show, however, that if it is utilised, fat is oxidised directly and does not undergo a preliminary conversion into carbohydrate ; if the latter change occurred, approximately 30 per cent, of the energy liberated by the oxidation of fat would not be available for mechanical work (Zuntz), and the mechanical efficiency would be lower on a fat than on a carbohydrate diet. Zuntz' view that fat and carbohydrate can serve equally well as sources of muscular energy was for' many years almost uni- versally accepted, the more so since it is in accordance with the common experience that work appears to be carried out equally 8 THE PHYSIOLOGY OF MUSCULAR EXERCISE efficiently in individuals whose diets are totally dissimilar as re- gards their content of fat and carbohydrate. Later evidence, however, has led many physiologists to consider that, provided it is available, carbohydrate is the main, and possibly the sole, source of muscular energy. In a recent study of muscular metabolism, Benedict and Cathcart (191 3) hav9 pointed out that it is unsafe to draw conclusions, from isolated experiments on the respiratory quotient ; and their own observations revealed a striking' lack of uniformity between the results of individual experiments. An average of their results indicates, however, that muscular work produces a small but definite rise in the respiratory quotient, whether the diet is rich or poor in carbohydrate. TABLE III. — Effect of Exercise on the Respiratory Quotient. (Benedict and Cathcart.) Preceding Diet. Date. Lying Before Work. During Work. Lying After Work. Carbohydrate — rich Average Jan. 24 >. 25 „ 26 Feb. 14 .. 15 „ 16 0-87 ■80 •86 'V •81 ■87 0-87 •92 •83 •93 •95 •88 0^76 78 79 78 •8r •76 0-85 ■90 78 Carbohydrate — poor Average Jan. 17 „ 18 » 19 Feb. 7 ,. 9 77 77 77 •84 •81 79 •87 74 74 ■91 ■86 •82 73 •70 71 •82 •76 77 79 . •82 75 Severe and prolonged exercise depletes considerably the re- serve of carbohydrate in the body, and if, as Zuntz supposed, the active muscles use fat and carbohydrate in the proportions pre- sented to them, the rapid diminution of available carbohydrate should result in a gradual fall of the respiratory quotient during prolonged work. This did occur in some of Zuntz' experiments, but Benedict and Cathcart find, on the contrary, that the respira- tory quotient actually rises more during heavy prolonged work than during light or moderate work. When the work is finished, however, the respiratory quotient usually falls below that observed THE SOURCES OF MUSCULAR ENERGY g previous to the performance of work (Table III.). Benedict and Cathcart explain this by supposing that the muscles, when resting after work, are again oxidising fat and carbohydrate in the pro- portions presented to them, and that, owing to the reduction of the store of carbohydrate in the body during the work, less carbo- hydrate is available after a period of severe work. The evidence presented by Benedict and Cathcart leads them to conclude that the metabolism of active muscle differs qualitatively as well as quantitatively from that of resting muscle, and that, whatever may be the character of the diet, the energy.of muscular work is derived mainly from carbohydrate. But, as Benedict and Cath- cart are careful to point out, it does not prove that carbohydrate is the sole source of muscular energy. Experiments on Isolated Muscle. The problem has been approached from a very different start- ing point by Fletcher and Hopkins, by A. V. Hill and by others. Working with isolated frog's muscle, Fletcher and Hopkins (1902-1917) have shown that the chemical changes taking place during muscular contraction occur in two stages, of which the first is the formation of lactic acid, and the second is its removal. The production of lactic acid, which culminates in a muscular contrac- tion, is a non-oxidative process, and can take place in the absence of oxygen ; its subsequent removal is an oxidative process and demands an adequate supply of oxygen. Fletcher and Hopkins consider that the appearance of lactic acid precedes, and is inti- mately bound up with, the mechanical shortening of the muscle, whereas its oxidation is effected after the contraction is over, and brings about the return of the muscle to its former resting condi- tion. Their results have been confirmed and supplemented by A. V. Hill (191 1-1913), who found that, in the absence of oxygen, the production of heat in an active muscle is limited to the period of contraction, whereas, in the presence of oxygen, the production of heat continues for some time after the contraction. As the outcome of these investigations, the conclusion has been reached (A. V. Hill, Fletcher, and Hopkins) that the process of muscular contraction consists essentially in the transformation of some form of potential energy into surface energy, and that this change gives rise to a condition of tensile stress within the muscle, which therefore tends to shorten and to perform work ; lo THE PHYSIOLOGY OF MUSCULAR EXERCISE if it is not allowed to shorten, the surface energy is dissipated as heat. But some difference of opinion exists as to the form in which its potential energy is stored in the muscle. A. V. Hill holds that some unstable chemical complex is present, which, under the influence of a stimulus, is decomposed, lactic acid being formed, and the energy, furnished by this decomposition, being converted into surface energy. After the contraction is over, the lactic acid is once more built up into the chemical complex, the energy required for fhis purpose being obtained from the oxida- tion of fat or carbohydrate within the muscle. Fletcher land Hopkins, on the contrary, consider that the potential energy resides " in a particular condition of a physico-chemical system," and that a system of colloidal fibrils or longitudinal surfaces, such as is assumed to exist in muscle, possesses a potential of energy which may be discharged as work or heat when H' ions are brought into relation with it. They believe that the formation of lactic acid from glucose, by setting free H" ions, initiates the discharge of part of this energy in the form of a muscular con- traction ; the return of the colloidal system to its former resting condition, and the restoration of Jts potential energy, are effected at the expense of the energy furnished by the oxidation of lactic acid after the contraction is over. * There is every reason to believe that in muscle, as elsewhere in the body, lactic acid appears as an intermediate stage in the combustion of carbohydrate, and Parnas and Wagner (1914) have shown that the appearance of lactic acid coincides with a diminution of the carbohydrate content of isolated muscle. But, in muscle, to quote Fletcher and Hopkins, lactic acid has " its special r61e to play in connection with the muscle machinery. In the evolution of muscle it would appear that advantage, so to speak, has been taken of this acid phase in carbohydrate degrada- tion, and that, by appropriate arrangement of the cell-elements, the lactic acid, before it leaves the tissue in its final combustion, is assigned the particular position in which it can induce those tension changes upon which all the wonders of animal movement depend." The logical deduction, which springs from this conception of the nature of muscular contraction, is that the carbohydrate stored in the' muscles, and elsewhere in the body, furnishes the main reservoir of energy upon which the muscles draw for the carrying THE SOURCES OF MUSCULAR ENERGY ii out of work. This inference is supported by the observations of Winfield (1915), who has found that fat does not diminish in amount in excised frog's muscle, when this is made to contract in air or in an atmosphere of hydrogen! There is no clear evidence that, either in Winfield's experiments or in those of Fletcher and Hopkins, the store of carbohydrate in the muscles was exhausted, and these experiments do not exclude fat as a possible source of muscular eneilgy. But they do suggest that, so long as carbohydrate is available, it alone is utilised to pro- vide the energy of muscular work. Experiments on the Heart. Additional evidence bearing on the sources from which the epergy of muscular work is derived has been furnished by Evans (1912, 1914) in his study of the metabolism of the heart ; and this evidence gains in value from the fact that the muscle was provided with its normal blood-supply. Using the heart-lung preparation, in which the circulation of the blood is limited to the heart and lungs, Evans found, in confirmation of Rohde (1910), that the respiratory quotient of the isolated heart varies within the same limits, and under the same conditions, as that of the body generally. The isolated heart, therefore, is able to oxidise the same materials as those used by the body as a whole. He then calculated from the respiratory quotient of the heart that the energy expended by the heart was derived to a much greater extent from fat than from carbohydrate. Even after the addition of glucose to the circulating blood, only just over a third of the total energy of the heart was obtained from the oxidation of carbohydrate, although the respiratory quotient was distinctly raised by the addition of glucose. TABLE IV. (EVANS.) Oxygen Consumed in C.C. per kgm. o£ Work. Output of Car- bonic Acid in C.C. per kgm. of Work. Respiratory Quotient. Exp. (i) Before adding glucose After , „ „ Exp. (2) Before „ After „ „ 14 l8-5 15-2 17-3 lO-I 147 I2"I 14-3 , 0723 078s 079s 0-826 12 THE PHYSIOLOGY OF MUSCULAR EXERCISE • In calculating the proportion of fat and carbohydrate used by the heart, Evans assumes that about 1 5 per cent, of the total energy of the heart is derived from protein, and that the oxida- tion of fat, carbohydrate, and protein is complete ; but the neces- sity for making these assumptions does not affect the general accuracy of the results. Unless it is assumed that the metabolism of cardiac muscle differs fundamentally from that of skeletal muscle, and of this there is no evidence, there appear to be three possible interpreta- tions of these results. The first is that much of the carbohydrate used by the heart is derived from fat ; although Chauveau believed this to take place, the evidence against its occurrence is very strong. The second possibility is that, although fat is being oxidised in the heart-muscle, the energy derived from this process is utilised, not in the contractile process, but in some other way. The third possibility is that fat does actually serve as an important source of muscular energy. Evans' experiments do not furnish any decisive argument in favour of either of these two possibilities, since the effect of glucose upon the respiratory quotient might be accounted for on the assumption that the muscle avails itself of the larger supply of carbohydrate to use a greater proportion of carbohydrate as compared with fat. It is possible, therefore, to maintain that the oxidation of fat observed in these experiments formed part of the basal meta- bolism of the heart, and that the energy required for the con- tractile act was obtained entirely at the expense of carbohydrate. But, in some of Evans' experiments, the respiratory quotient was so low that the energy derived from carbohydrate must have barely equalled that appearing as external work done by the heart ; in these circumstances, fat must also have served as a source of energy. If, as these experiments seem to show, the energy derived from the oxidation of fat as part of the basal metabolism of the heart muscle can be diverted at any moment for utilisation in the contractile process, it seems rather arbitrary to assume that fat is not always being drawn upon for this purpose. At first sight, Winfield's observations would appear to preclude this inference, but Winfield worked with excised muscles, whereas, in Evans' experiments, the heart was receiving its normal blood-supply. It may be that, under the conditions of Winfield's experiments, the tension or "pressure head" of THE SOURCES OF MUSCULAR ENERGY 13 oxygen, though sufficient for the oxidation of carbohydrate, is inadequate for the combustion of fat, and that fat demands for its combustion an intensity, so to speak, of oxygen-supply which can be attained only when the normal circulation is present. The fact that, on occasion, the heart can obtain practically the whole of its energy from fat, with no appreciable loss of efficiency or waste of energy, is readily intelligible on the as- sumption that the normal heart draws on fat to some extent for this purpose. This is the case in the isolated, diabetic heart in which, as Starling and Evans (191 4) have shown, the respiratory quotient is very low, its average value being 0708. The work of these hearts, which was nearly equal to that of a normal heart, must have been effected almost entirely at the expense of fat (or of protein). This must also be the case during muscular exercise after prolonged starvation, when the carbo- hydrate store of the individual has been exhausted. Unfortun- ately direct evidence as to the effect of muscular work upon the respiratory quotient under these conditions is very scanty ; and, since glycogen 9.ppears to be present in the body, even after prolonged starvation (Prausnitz), the possibility of carbohydrate being used in these circumstances must be taken into account. Conclusion. It seems clear from the evidence of Benedict and Cathcart on the respiratory quotient, and that of Fletcher and Hopkins on isolated muscle, that, when both fat and carbohydrate are available, the muscles display a marked preference for carbo- hydrate as a source of energy. At the same time there is good reason for believing that fat is also utilised for this purpose, although the extent to which this occurs is still uncertain. The processes taking place during a muscular contraction are so intimately bound up with the momentary appearance of lactic acid and its subsequent oxidation that, at first sight, the conclu- sion just stated appears hardly compatible with Fletcher and Hopkins' conception of the nature of muscular contraction. But Bayliss has pointed out that it is not the production of lactic acid as such, but the appearance of hydrogen ions, which initiates the act of contraction, and there is no difficulty in believing that the 14 THE PHYSIOLOGY OF MUSCULAR EXERCISE production of hydrogen ions can occur at some stage in the com- bustion of fat. In that case, the appearance of lactic acid during muscular contraction ceases to have any peculiar significance, and the pre- ferential utilisation of carbohydrate by the muscles during exercise may be attributed to the readier mobilisation of carbohydrate, and perhaps to the more rapid disruption of glucose as compared with fat, rather than to any absolute necessity for the presence of lactic acid to bring about the act of contraction. The Mechanical Efficiency of the Body. The proportion of the total expenditure of energy during muscular exercise, which appears as external work, represents the mechanical efficiency of the bodily machine. The total production of energy in \ given time may be determined by means of the Atwater-Benedict calorimeter, or by measuring the consumption of oxygen. Zuntz calculated that the absorption of i litre of oxygen represented the produc- tion in the body of from 4-6 to 5 calories according to the character of the material oxidised, the value varying directly with the respiratory quotient. This corresponds closely with the figure i gramme oxygen consumption = 3'4 calories which was obtained by Benedict and Joslin (igio), since i litre of oxygen weighs i'43 grammes. If the external work done by , the subject is measured, it, too, can be calculated in calories from the equation i calorie = 425 kilogrammetres ; these data will give the mechanical eiBciency of the body. The efficiency (E) of the body is obtained from the equation E = j^ , where a = actual work measured and b = total ex- o penditure of energy in a given time. This is termed the £yoss efficiency, and is often taken for a period of twenty-four hours. A knowledge of the gross efficiency is of great value, as Benedict and Cathcart point out, for determining the energy output of a body of labourers and artisans working under the ordinary conditions of life, and for ascertaining the nutritional requirements of bodies of men carrying out severe muscular work. But, since a con- siderable part of the day is spent in rest, during which time there is an expenditure of energy unaccompanied by external work, the gross efficiency does not fairly represent the true potentiality of the body for severe work. To determine the possible efficiency of the body, the energy required for the maintenance of the body, when the individual is at rest, should be deducted from the total expenditure of energy during the working period. When this cor- THE MECHANICAL EFFICIENCY OF THE BODY 15 rection is made, one obtains a value, called the net efficiency, from the formula — , in which a is the amount of work performed, b- c b is i^e total expenditure of energy for the period during which the work was performed, and c is the expenditure of energy during a similar resting period. The following figures, taken from Benedict and Cathcart, show the maximum gross and net effici^cies in six individuals : — Subject. Gross E£Bciency. Net Efficiency. I 19-4 231 2 17-8 20-4 3 i8-6 21-6 4 ig-S 227 5 i8-3 20-8 6 21 "2 25-2 The work done in these experiments was carried out on a bicycle ergometer. Benedict and Cathcart conclude that the average net efficiency of muscular work is about 21 per cent., and figures varying from 20 to 28 per cent, have been found by many other observers (Zuntz, Durig, Rubner, Macdonald). An in- teresting fact brought out by Zuntz is that the mechanical effi- ciency varies with the kind of work performed. It is greater, for example, for mountain climbing than for walking on the level. The chief conditions which influence the net efficiency of muscular work are training, the speed with which the work is performed, and fatigue. The effects of training are shown by Zuntz' observation that, in subjects working on a bicycle ergo- meter, the efficiency varied from 20 per cent, in the untrained man to 25 per cent, in the trained subject. Further, Benedict and Cathcart found that, in a very highly trained man, not only was the average efficiency always greater than that of ordinary individuals, but that the maximum net efficiency at times reached 33 per cent, a figure which was never attained by the untrained person. The speed at which work is carried out has a striking influence upon the efficiency of the individual. Macdonald (1914) has shown that there is an optimum rate of work at which the effi- ciency is greatest ; and the same conclusion has been reached by Benedict and Cathcart, who found that, when a constant amount i6 THE PHYSIOLOGY OF MUSCULAR EXERCISE of work was performed at varying speeds, the optimum efficiency was reached at a very moderate speed, and that the efficiency fell off very rapidly when the speed was increased. In their ex- periments the subject pedalled a bicycle ergometer at varying rates. His optimum efficiency was obtained with a speed of seventy revolutions of the ergometer per minute, and the following table shows the effect of increasing the number of revolutions, the total amount of work done being constant : — TABLE V. Revolutions per Minute. Heat Equivalent of Work Done. Net Efficiency. (1) 71 (2) 108 1-57 1-58 24-5 15-6 One of the chief advantages of training is improved co-ordina- tion of the muscular movements, and the elimination of useless and ineffective movements, the result being that a given amount of work can be performed with a smaller expenditure of energy. It is clear, therefore, that the nervous system, which brings about these changes, is largely responsible for the higher mechanical efficiency of the trained man. Again, perfect co-ordination due to constant practice is probably the explanation of the fact that walking is performed more economically than almost any other form of exercise. On the contrary, exercise to which a man is unaccustomed is usually carried out very inefficiently. The nervous system also plays an important part in deter- mining the relation between the rate at which a man works and his mechanical efficiency. The bodily machine possesses a natural rhythm, which is set by the central nervous system, at which a man works most effectively and with the least fatigue ; and the process known as " getting into one's stride " probably involves the adjustment of the speed of work to the natural rhythm of the individual. Doubtless this rhythm is susceptible to modification by training, and a man may, as a result of practice, attain his optimal efficiency at a higher rate of working than would otherwise be the case. But this can occur only to a limited extent ; and the study of fatigue among industrial workers has made it clear that, in so far as it disturbs this rhythm, THE MECHANICAL EFFICIENCY OF THE BODY 17 the process of " speeding-up " of workers defeats its own end by lessening their ' mechanical efficiency and by inducing excessive fatigue. It must be remembered, however, that the worker is also inefficient if the rate of work is slower than the natural rhythm of the individual. It follows, then, that, from an in- dustrial point of view, the most effective workers are those whose natural rhythm of work is most rapid, since they can perform more work in a given time without fatigue or loss of efficiency. So far as the muscles are concerned, the optimum speed of work is that which allows the recovery process, that is to say, the restoration of potential energy, to keep pace with the ex- penditure of energy in the muscles and heart. If the speed at which work is performed is such that this balance is upset, the accumulation of waste products and the diminishing store of potential energy lessen efficiency by inducing fatigue. But, since the fatigue induced by exercise has its seat primarily, and often exclusively, in the central nervous system, the decline in efficiency, when work is performed at an excessive speed, is probably due quite as much to less effective co-ordination of movement as to- changes in the muscles themselves. There is indeed very little evidence that, under normal con- ditions, the metabolic conditions of the muscles alter sufficiently to exert any marked influence upon the mechanical efficiency of the body. Zuntz (1903) found that a dog, trained for walking on the level, performed a given amount of work more .economic- ally when walking on the level than when climbing. The dog was then trained to ascend an incline, the result being that, after two years, its mechanical efficiency was greater for climbing than for walking on the level. This experiment has been regarded as showing that individual muscles, when trained, work more efficiently than untrained muscles, but the result may equally well have been due to more complete co-ordination of movement as the outcome of training. It is probable then, that, under the ordinary conditions of life, the efficiency of the nervous system is the chief factor upon which depends the mechanical efficiency of the body, and that the extent to which training improves the efficiency of the in- dividual is mainly determined by the reactive powers of his nervous system. Another factor which influences the optimal speed of working t8 THE PHYSIOLOGY OF MUSCULAR EXERCISE is the amount of work which has to be carried out. Work at high speed can only be kept up for a short time, since the onset of fatigue rapidly lowers the efficiency of the body ; and the trained worker learns to adjust the rate at which he works to the amount which he has to do. Every climber, for example, knows that the Swiss guide sets a pace which at the beginning of the day appears to him too slow and at the end of the day seems too fast, the truth being that the guide has learned by experience the pace which yields the optimum efficiency. The Temperature of the Body During Exercise. In addition to that appearing as external work, part of the energy expended by a man during muscular exercise is utilised by the heart, by the respiratory muscles, and in other ways. But, even taking this into account, a large fraction of the energy set free in the body during exercise is for practical purposes wasted, since it is degraded into heat and lost from the skin and lungs. The loss of heat, however, does not quite equal its produc^tion, and the temperature of the body rises until a balance is reached at a higher level. The first reliable observations on the temperature during exercise were carried out by Pembrey and Nicol (1898), who pointed out that, in order to measure accurately the body tem- perature, it is necessary to take either the rectal temperature or that of the urine as it leaves the bladder ; temperatures taken in the mouth are quite unreliable. Pembrey found that, during exercise, the temperature may reach 38"9° C. (102° F.) ; and a temperature of 104° F. or even 105° F. has been recorded by L. Hill (1910). Pembrey has also emphasised the important fact that the rise of temperature depends, not only on the severity of the exercise, but also on the rate at which heat is lost from the body. The loss of heat is modified by the temperature and humidity of the surrounding air, by the amount and nature of the clothing worn, and by the presence or absence of wind. The influence of some of these factors is indicated by the following figures (Pembrey), obtained from a nuipber of soldiers who marched the same distance on a hot day and on a cold day: — TEMPERATURE OF THE BODY DURING EXERCISE 19 TABLE VI. March of Seven Miles, Average In- crease in Pulse- rate per Minute. Average In- ■ crease in Rectal Temperature. External Temperature. Dry Bulb. Wet Bulb. Hot day . . . Cold day 62 14 1-4° F. 0-8° F. 79° F. 45° F. 67-5° F. 38° F. The influence of the temperature and humidity of the ex- ternal air upon the loss of heat from the body, and, therefore, upon the temperature of the body during exercise, is very con- spicuous in fat individuals. Owing to the dense covering of subcutaneous fat, the body loses heat less readily (Lusk), and the temperature rises to a greater extent, in fat, than in thin, subjects taking the same amount of exercise. Among the comparatively few continuous records of the rectal temperature during severe exercise are those of Benedict and Cathcart (Eig. i). The most striking features, which they observed, are the rapidity with which the temperature rises at the beginning of exercise and falls after its conclusion. The fall in temperature during the exercise in one experiment (Dec. 22) coincided with a diminution in the muscular work performed ; and it is very probable that, other conditions being constant, the rise of temperature during the exercise is proportional to the intensity of the muscular work. The most important effect of the higher temperature is that it increases the total metabolism of the body, and, therefore, the consumption of oxygen. This effect may be very considerable. Linser and Schmid (1904) found that a rise of 3° C. in the temperature of the body led to an increase of 40 per cent, in the output of carbonic acid. The more active metabolism means more complete oxidation of waste products, the prevention of excessive accumulation of food-stuffs, and a general quickening of the vital- ity and functional power of every organ, which adds to the well- being and vigour of the whole body. It is of interest to note that it is the oxidation of fat and carbohydrate which is increased, and not that of protein (Graham and Poulton), whereas, in fever, the breaking down of protein is abnormally large. Its beneficial effects are perhaps best seen in thfc case of the muscles. Lagrange (1889) suggested that a rise of temperature 20 THE PHYSIOLOGY OF MUSCULAR EXERCISE increases the efficiency of the skeletal muscles, and that the advantages of a preliminary canter, or of warming up to work, for instance, are due to a rise of temperature in the active muscles. As Pembrey has observed, however, other factors have also to be taken into consideration, such as an increased blood-flow through the muscles, and adjustments of the heart and respiration. sv.a OT.8 37.7 37.« S7.6 1, ,.'. ,_ \ f ''\ \ IS// 1 \ \ 0£C DLC DLC 20- 2/ ~ Z2.- \ V^ s \ J7.4 S7.3 37.2 37.1 97.0 \ ► y> f^ \ Y '-' \ ' / / \ \ \ r 7^ \\ \ 1 1 ^ \ 38.8 ' ^ \ 36L7 / V V / \ \' % 1. / n: ^k // \ s \ 36.8 / \ s^ A ^^ y ■^ ■^N s> f \ ■■— ».i W>.\ s/ AM.8.20 8.30 8.40 8.60 9.00 9.10 9.20 9.30 9.40 9.901O0010.1010.2010.3O10.40ia5011.0On.l0U.20U.3011.4011.5012.00 Fis. I. — Continuous records of the rectal temperature obtained by thermal element during severe muscular work (Benedict and Cathcart). Arrows indicate beginning and end of exercise. Bayliss(i9i5) has pointed out that the transformation of potential into kinetic energy in the first phase of muscular contraction has a negative temperature coefficient, since it depends upon the development of surface energy and is not an oxidative process, whereas the restoration of energy has a positive coefficient, which is much larger than the negative coefficient of the physical change. The result is that a moderate rise of temperature will increase the oxidative removal of lactic acid and the restoration of poten- tial energy to the muscles, while not appreciably lessening their SUMMARY 21 power to transform potential into kinetic energy. In this way a rise of temperature during exercise is favourable to muscular work because, by, preventing the accumulation of lactic acid, it increases the efficiency of the muscles and lessens their liability to fatigue. It is possible that this fact has some bearing on the relationship between the speed of work and its efficiency. Apart from its effects upon metabolism, a slight rise of temperature heightens the excitability of the nervous system, or at least that of the medullary centres, with the result that the pulmonary ventilation, the pulse-rate, and the activity of the vaso- motor centre, are greater than would otherwise be the case, and the circulatory and respiratory adjustments accompanying mus- cular exercise are rendered more effective. At the same time, by lessening the affinity of haemoglobin for oxygen, it enables the dissociation of oxyhaemoglobin, as the blood flows through the tissues, to take place more completely. These effects of a rise of body temperature are possibly to some extent incidental, rather than necessary, concomitants of muscular exercise and not essential for its efficient performance, since, for a given amount of exercise, the rise of temperature appears to be less in the trained than in the untrained man. But the range of temperature within which they occur is con- siderable. In one of the Marathon races, the runner who was least distressed at the end of the race had a temperature of 104° F. (Savage and Barasch). There is no doubt, however, that a rise of temperature beyond a certain point is actually harmful to the body, and more especially to the nervous and vascular systems. This point, though varying in different individuals, usually appears to be reached when the temperature rises above 102° or 103° F. Graham and Poulton, who raised their temperature by means of external moist heat, felt no discomfort until the rectal temperature rose to 102° F. ; at this level restlessness, irritability, and dyspnoea appeared. The ill-effects become more marked as the temperature of the body rises until they culminate in the dis- organisation of the bodily functions which constitutes heat-stroke. Summary. Under normal conditions protein does not serve as a source of energy during exercise, and the energy expended by the 22 THE PHYSIOLOGY OF MUSCULAR EXERCISE muscles must ultimately be derived from the oxidation of either fat or carbohydrate. The rise of the respiratory quotient during exercise points to a preferential utilisation of carbohydrate by the muscles, but does not exclude the possibility that they may also obtain energy from the oxidation of fat. In isolated muscle, the production and subsequent removal of lactic acid, which is an ^intermediate product of carbohydrate metabolism, are so intimately bound up with the process of muscular contraction that Fletcher and Hopkins regard carbo- hydrate as being normally the main source of muscular energy. This conclusion is supported by the observation that prolonged activity of isolated muscle diminishes its content of carbohydrate, but not of fat. The isolated heart, if provided with its normal blood-supply, obtains the greater part of its energy from fat The general conclusion is reached that, when both fat and carbohydrate are available, the skeletal muscles display a prefer- ence for carbohydrate as a source of energy, but that fat is also utilised for this purpose. The net efficiency of the bodily machine usually varies from 20 to 25 per cent, and may occasionally reach 33 per cent. The chief conditions which affect the mechanical efficiency of the body are training, the speed with which work is performed, and fatigue. The body possesses a natural rhythm which is set by the nervous system, and a man works most efficiently when his speed of working corresponds with this rhythm. The extent to which the temperature of the body rises during exercise depends, partly on the severity of the exercise and partly upon the temperature and humidity of the atmosphere and other conditions. The rise in temperature increases the metabolic activity of the body, and adds to the effectiveness of the circulatory and respiratory adjustments occurring during exercise. By these means it promotes the more efficient carrying out of muscular work. CHA.PTER III. THE RESPIRATORY CHANGES DURING EXERCISE— THE REACTION OF THE BLOOD DURING EXERCISE. The evidence derived from the study of isolated muscles makes it clear that they normally contain a considerable store of potential energy, which can be transformed into work and heat in the absence of oxygen. For example, an excised frog's muscle, kept in nitrogen, can give a maximal contraction every five minutes for two hours and a half before showing signs of fatigue (Fletcher, 1902). But this process, at least in mammalian muscle, comes to an end comparatively quickly, unless the energy of the muscle is renewed as rapidly, or almost as rapidly, as it is used up ; and this is normally effected by the oxidation of fat and carbohydrate. In health, an ample reserve of fat and carbo- hydrate is always present in the body, which can be and is drawn upon during muscular work. The disappearance of glycogen from the liver during exercise has been repeatedly demonstrated in animal experiments ; and Benedict and Cathcart (191 3) have recently calculated that in one of their subjects, during 262 minutes' work, 368 grammes of glycogen were oxidised. The doctrine that the oxygen needed for these oxidations either is, or can be, stored up in the muscles in excess of their immediate needs has been finally disproved by Fletcher and Brown (19 14), and, at any moment, the supply of oxygen avail- able for the tissues barely exceeds the demand. Indeed, in this respect, the body lives practically from hand to mouth, and no hoarding up of oxygen appears to be possible. Muscular work at once increases the consumption of oxygen, the consumption of oxygen per minute varying almost directly with the work done in the same time (Fig. 2) ; and the relationship is so close that the oxygen-consumption of the body during exercise is now usually taken as a measure of its intensity (Benedict and Cathcart, 1913, Lindhard, 1915, Boothby, 1915). 23 24 THE PHYSIOLOGY OF MUSCULAR EXERCISE Since a brief and moderate shortage of oxygen rapidly inter- feres with the performance of muscular work or even renders it impossible, it is evident that the supply of oxygen to the body during exercise must normally keep pace with its consumption. This is ensured through the intervention of a variety of adjust- ments in the respiratory and vascular systems ; and these fall into two groups. In the first place, at the beginning of exercise 3500 3000 izsoo >ZOt)0 O O U I 1500 «> 1000 o soo ■1 ^^ 700 400 600 800 1000 1200 Kilogramme Metres of Work. FiQ. 2. — (Constructed from Lindhard's data.) 1400 1600 or, if this is carried out under emotional excitement, even before the exercise starts, impulses pass from the higher centres to the medullary centres, and bring about a rise of blood-pressure, deeper breathing, and greater frequency of the pulse ; and the blood-supply to the heart, brain, and muscles is, thereby, at once increased. In the second place, as a direct or indirect result of the mechanical and chemical activity of the skeletal muscles, other circulatory and respiratory adjustments are brought into action to reinforce and supplement the initial changes induced through THE RESPIRATORY CHANGES DURING EXERCISE 25 the medullary centres. The nature of these processes, and the means by which they are correlated with the intensity of the muscular work, may now be considered in some detail. The Respiratory Changes During Exercise. The part played by the respiratory mechanism during exer- cise is twofold. On the one hand, it is called upon to provide in the lungs the additional oxygen required by the body ; on 70 60 S 50 a. 40 030 20 10 X SCO 3500 1000 1500 2000 2500 3000 Oxygen-Consumption: c.c. per Minute. Fig. 3. — Relation between consumption of oxygen and pulmonary ventilation (con- structed from Lindbard's data). the other hand, it serves as a delicate mechanism for regulat- ing the reaction of the blood, and for preventing the acids pro- duced in the active muscles from causing any gross change in the reaction of the blood. The amount of oxygen which can pass into the blood is de- termined primarily by the total ventilation of the lungs ; and the closeness of the relationship between the pulmonary ventilation and the amount of work performed (as measured by the oxygen- consumption of the body) has recently been brought out by Means and Newburgh (1915), by Krogh and Lindhard (1917), 26 THE PHYSIOLOGY OF MUSCULAR EXERCISE and by Boothby (1915), who find that the ventilation of the lungs is approximately a linear function of the oxygen-consump- tion of the body (Fig. 3 and Table VII.) '. — TABLE VII. (BpOTHBY.) Oicygen-Consumption. Total Pulmonary Ventilation. c.c. per Min. Percentage Increase, 175 c.c. = 100. Litres per Minute. Percentage Increase, 5'5 = 100. / 320 448 Work ■ 559 608 i- gi2 100 1057 182 256 320 347-4 521 5-5 6-7 9-8 12-8 15-5 16-8 24-1 100 121-8 178 233 282 305-5 438 The accuracy of the adjustment between the amount of oxy- gen used by the tissues, and that supplied by the lungs, is equally clearly shown by the trivial alteration in the percentage of qxy- gen in the alveolar air, however violent the exercise may be. During heavy muscular work the consumption of oxygen may reach 3 litres per minute, and the pulmonary ventilation may be 50 to 100 litres per minute. Lindhard's observations render it probable, however, that, even under these conditions, the tension of oxygen in the alveolar air is quite sufficient to allow the blood to become fully saturated during its passage through the lungs ; and there is no evidence that, in the normal individual, the re- spiratory mechanism ever fails to provide an adequate supply of oxygen for the needs of the body. TABLE VIII. (LiNDHARD.) Ventilation. Litres per Minute. Oxygen in Expired Air. Oxygen Cons., c.c. per Minute. Alveolar CCj at o" and 760 mm. Hg. 14-2 32-9 46-8 68-2 17-55 per cent. 15-74 16-07 16-87 „ 410 144I 1893 2250 3-75 per cent. 5-43 5-30 478 „ Further, the increase in the expansion and mean capacity of the lungs during exercise, by increasing the surface area of the alveoli (M. Krogh, 19x5), permits oxygen to diffuse more readily from the alveolar air into the blood than during rest. In this THE RESPIRATORY CHANGES DURING EXERCISE 27 respect, the conditions are more favourable to the passage of oxy- gen into the blood during exercise than during rest. The Regulation of Respiration During Exercise. It may be concluded that, when a man performs muscular work, the activity of his respiratory centre, and therefore the supply of oxygen in the lungs, varies directly with the severity of the work ; and the question at once arises what is the nature of the mechanism by which this correlation is effected ? Before attempting to answer this question, it is necessary to consider the conditions which bring about greater pulmonary ventilation during exercise. It is generally admitted that the normal stimulus to the respiratory centre is the chemical composition of the blood. The response of the centre to this stimulus depends, however, not only on the magnitude of the stimulus, but also on the sensitiveness of the centre ; and it will be convenient in the first instance to discuss separately these two factors. The Stimulus to the Respiratory Centre. The work of Miescher (1885) and of Haldane and Priestley (1905) led them to believe that the normal stimulus to the respiratory centre was the tension of carbonic acid in the arterial blood. A little later, Haldane and Boycott (1908) suggested that the actual stimulus to the respiratory centre is not the ten- sion of carbonic acid but the H" ion concentration of the arterial blood. This has been confirmed by the more recent work of Winterstein (1911) and of Hasselbalch (1912). The latter showed that, by altering the diet, the tension of carbonic acid can be varied, although the reaction of the blood remains con- stant; and he concluded that the pulmonary ventilation is so adjusted as to maintain the H* ion concentration of the blood constant. According to this view, which has been generally accepted, carbonic acid excites the respiratory centre merely because it acts as an acid when in solution, and the activity of the respiratory centre depends entirely upon the H' ion con- centration of the blood. It follows that, provided the sensitive- ness of the respiratory centre remains constant, the pulmonary ventilation will vary with, and will furnish an index of, the H • ion concentration of the blood. 28 THE PHYSIOLOGY OF MUSCULAR EXERCISE Every watery solution contains both H- ions and (OH') ions, and in a perfectly neutral solution, such as pure water, the concentration of the two ions is equal, each of them having a concentration of i x lo-' at 25° C. In an acid solution, the H. ions are in excess of the (OH') ions, the converse b^ing the case in an alkaline solution. Since the product of the H • and (OH') ions in any solution is always the same, namely i x 10-", the reaction of the solution can be found by determining the concentration of the H- ions. If this is greater than i x 10-', the solution is acid, whereas if it is less than i x 10-', the solution is alkaline. The H- ion con- centration of a solution, often represented by the abbreviation Ch, is therefore a measure of its acidity ; it may also be expressed as its negative exponent, this being termed its Ph value. Thus the negative exponent of 3 x lo-^ is 7*52, and a solu- tion whose Ch is 3 x 10-* is said to have a Ph value of 7-52. It should be noted that the more acid the solution the smaller is its Ph value. Evidence has recently been brought forward, however, by Hooker, Wilson, and Connett (1917), and by R. W. Scott (1918), that this conclusion is not altogether correct, and that carbonic acid may act as a specific stimulus to respiration independently of its acid properties when in solution. Hooker and his co- workers found that the respiratory centre is excited to a greater degree by blood possessing a high tension of carbonic acid than by blood in which its tension is low, the H' ion concentration of the blood being the same in each case. Scott has shown that, under certain conditions, the respiratory activity does not run parallel with the reaction of the blood but varies with the ten- sion of carbonic acid. It is possible that these results occur only under special conditions, and it has yet to be proved that they hold good in the normal animal. There is, moreover, some doubt as to whether the method adopted by Scott for measuring the H • ion concentration of the blood is reliable. Tke Sensitiveness of the Centre. The sensitiveness of the respiratory centre is probably con- stant (Haldane) in the resting individual, although Lindhard has brought forward some evidence for the existence of slight seasonal variations. Krogh and Lindhard (191 3) have proved, however, that the greater pulmonary ventilation, which occurs at the out- set of exercise, can only be the result of increased excitability of the respiratory centre ; and they have given grounds for believing that it is brought about by the passage of impulses from the higher centres to the respiratory centre, simultaneously with the outflow of impulses to the skeletal muscles. Whether this change persists throughout the whole period of THE RESPIRATORY CHANGES DURING EXERCISE 29 exercise is still a matter of discussion. But the activity of the vaso- motor and vagus centres, as well as that of the respiratory centre, is modified at the beginning of exercise by impulses from the higher centres ; and, since such impulses almost certainly con- tinue to act upon the vaso-motor centre throughout the period of exercise, it is reasonable to believe that this is the case also as regards the respiratory centre, and that during exercise this centre is always more excitable than during rest. Again, the observations of Haldane (1905) make it clear that a rise of body- temperature heightens the excitability of the respiratory centre ; the rise of temperature during exercise must therefore en- hance the responsiveness of the respiratory centre to increased H* ion concentration of the blood. The hyperpncea or dyspnoea^ occurring during muscular exercise has, therefore, a twofold origin. On the one hand, the greater production of acid in the active muscles tends to increase the H' ion concentration of the blood, and Boothby has brought forward some indirect evidence that the change in the reaction of the blood is proportional to the severity of the work done. On the other hand, the excitability of the centre is heightened in the manner just described, and this change also is probably pro- portional to the amount of muscular work, since both the rise of body-temperature and the outflow of impulses from the higher centres to the respiratory centre will usually be greater during heavy work. Hence the correlation between the pulmonary ventilation and the severity of muscular work appears to depend partly upon the fact that the H" ion concentration of the blood varies with the activity of the muscles, and partly upon the correspondence between the intensity of the impulses sent out from the higher centres to the muscles and to the respiratory centre respectively. This relationship is obviously liable to be disturbed either by excessive production of acid in the active muscles, or by exaggeration of the excitability of the respiratory centre, a result which may follow upon an inadequate oxygen- supply. The extreme hyperpncea, which may be brought on by comparatively slight exertion in cases of " soldier's heart," for example, represents a disturbance of the normal relationship which is possibly caused by one or other of these means. A further consequence which follows upon the above line of argument is that, owing to the greater excitability of the 30 THE PHYSIOLOGY OF MUSCULAR EXERCISE respiratory centre, a comparatively trivial change in the reaction of the blood is needed in order to bring about a large increase in pulmonary ventilation. This conclusion is of significance, since the increased H- ion concentration of the blood during exercise has been credited with modifying the activity, not only of the respiratory centre, but of other centres and organs. It seenjs desirable, therefore, to refer to the factors which regulate the reaction of the blood, and to the extent to which this alters during exercise. The Reaction of the Blood. It is well known that the addition of fixed acid to blood or blood-plasma produces a much smaller change in its reaction than if the same amount of acid were added to pure water. The difference depends upon the fact that blood, or plasma, contains substances which react with the acid to form compounds dis- sociating to a very slight extent and, therefore, setting free very few H- ions. In virtue of their action in stabilising the reaction of the blood, and in preventing any gross change in its reaction when acid is added to it, these substances have been termed " buffer " substances. This buffer action was formerly attributed (Moore and Wilson, 1906) to the proteins in the plasma, but L. J. Henderson (1908) has shown that the power of protein to re- act with weak acids or alkalies does not come into play, except to a very limited extent, so long as the H* ion concentration of the blood is within the limits compatible with life. The only buffer substance of practical importance present in blood-plasma is sodium bicarbonate. When a fixed acid is added to blood, it reacts with sodium bicarbonate, setting free carbonic acid, but, owing to the very slight dissociation of H^COg, the addition of a considerable amount of strong acid, and therefore of a large number of free H- ions, results in a very slight change in its reaction. Hence the reaction of the blood, as L. J. Henderson slnd Hasselbalch (19 12) have shown, is represented by the equation HjCOo C„ = K j^ HCO ' ^" which the numerator indicates the concen- tration of HCOg ions, and is proportional to the tension of carbonic acid in the blood, the denominator is the amount of sodium THE RESPIRA TOR Y CHANGES DURING EXERCISE 3 1 bicarbonate in the plasma, and K is the dissociation constant of H2CO3. The addition of carbonic acid to blood in vitro alters its re- , action solely by increasing the number of H* and HCO3 ions, whereas fixed acid, when added to blood, increases its H- ion concentration by reacting with sodium bicarbonate, thereby lessening the amount of this salt in the plasma, and at the same time increasing the carbonic acid in the blood. It is clear that, if the tension of carbonic acid in the blood is kept constant, the reaction of the blood will vary inversely with the amount of sodium bicarbonate in the plasma, and that, on the other hand, if the bicarbonate remains unchanged, the reaction of the blood varies with the tension of carbonic acid. When the blood is circulating in the body, the respiratory centre at once reacts to the slightest rise in the H' ion concentra- tion of the blood, whether this is effected by an increase in the numerator or a decrease in the denominator of the equation Ch = K ^ firo ' ^^'^^ if the centre remains efficient, the reaction of the blood cannot alter greatly until the bicarbonate has almost entirely disappeared. For this reason, the bicarbonate of the blood has been termed its " alkali-reserve '' (Van Slyke). Other mechanisms also exist in the body which tend to pre- vent any undue depletion of the plasma bicarbonate. One is the kidney, which responds to every change in the reaction of the blood by varying the reaction of the urine. The other, which is probably of more immediate importance in minimising alterations in the reaction of the blood during exercise, is furnished by the red corpuscles and the tissues. Any addition of carbonic or other acid to the blood at once disturbs the balance between the ions in the plasma and those in the corpuscles and tissues ; and Zuntz (1861), and, later, Hamburgher (1897), have shown that, in these circumstances, an interchange of acid and basic radicles takes place between the plasma and the red cells, whereby acid enters the corpuscles, and base passes into the plasma, thus tending to restore its alkali-reserve. There is every reason to believe, as Van Slyke (191 7) points out, that a similar interchange takes place between the plasma and the tissues, in which phosphates form a buffer salt system. The importance of the part played by the tissues and red cells, in 32 THE PHYSIOLOGY OF MUSCULAR EXERCISE preventing an excessive fall in the bicarbonate of the blood- plasma during exercise, will depend upon the rapidity with which this interchange occurs, but it is probable that, at least during prolonged exercise, it contributes considerably to checking any marked change in the reaction of the blood. The Reaction of the Blood during Exercise. The reaction of the arterial blood during exercise has never been directly investigated, but the observations of Douglas and Haldane (1913) have yielded data from which it is possible to calculate approximately the maximum extent to which this may alter during exercise. They found that, in the resting subject, a rise of i '6 mm. in the alveolar tension of carbonic acid increases the total pulmonary ventilation by 10 litres a minute; and their observation has been confirmed in the later work of Campbell, Douglas, and Hobson (1914). Taking this figure in conjunction with Hasselbalch and Lundsgaard's (191 2) work on the relation between the alveolar tension of carbonic acid and the Ch of the blood, they point out that it represents an increase of 0-13 x lo"* in the Ch of the arterial blood, or a change of 0'02 in the P„ of the blood. Assuming, first, that this relationship holds good whatever the pulmonary ventilation may be, and, second, that the excitability of the respiratory centre remains constant, it is only necessary to determine the pulmonary ventilation during exercise in order to measure the effect of exercise upon the reaction of the blood. The range of pulmonary ventilation is very large, and a short period of violent exercise, such as 100 yards' race, may lead to a ventilation of 150 litres per minute or even more. But, since a man may run 1 00 yards without taking a breath, the ex- treme dyspnoea, thereby produced, takes place after the exercise is over, and probably could not be maintained for any length of time. During less severe work, which can be carried on for some time, the pulmonary ventilation does not usually exceed 100 to 120 litres per minute, and this figure is probably near the limit reached by most individuals during severe continued work. If the premises just stated are correct, an increase of 1 00 litres in the pulmonary ventilation would result from a rise of i'3 x io~* in the C„ of the blood which is equivalent to a decrease of 0'I5 in its P„ value. But, owing to the greater sensitiveness of the THE REACTION OF THE BLOOD DURING EXERCISE 33 respiratory centre during exercise, a much smaller change in the reaction of the blood would probably suffice to bring about such an increase in the pulmonary ventilation. The range of varia- tion in the P„ value of arterial blood during exercise, unless this is very severe, is therefore very small, being in all probability con- siderably less than 0*15. The only other observations bearing upon this question are those of Barcroft (19 14), who availed himself of the fact that any increase in the €„ of the blood, by lessening the affinity of haemo- globin for oxygen, alters the form of the dissociation curve of oxy- haemoglobin. One of Barcroft's experiments consisted in climb- ing 1,000 feet from sea-level in half an hour; and he potes that the rate of climbing entailed no sort of distress, and that " roughly speaking this meant going up at the fastest rate at which respira- tion could comfortably be performed through the nose ". At the end of the walk samples of his blood and alveolar air were col- lected. The carbonic acid tension of the alveolar air was 35 mm. Hg, and the blood, when exposed in a tonometer to this tension of carbonic acid and to an oxygen tension of 27 5 mm. Hg, be- came 40 per cent, saturated. The following figures show the effect of the exercise upon the affinity of Barcroft's blood for oxygen : — Alveolar CO, Tension. Oxygen- Tension. Percentage Saturation of Blood with O2. Value of K. After the ascent . Normal .... 35 mm. 40 27-5 27-5 40 per cent. 53 ,> 0-000168 0*000292 In order to arrive at the change in the reaction of the blood which would cause this decrease in the affinity of haemoglobin for oxygen, Barcroft makes use of what is known as the Barcroft-Peters curve (Fig. 4), which shows the Ph of the blood re- presented by the negative logarithm of any given value of K. K is a constant in the equation' -^' = ^ , where j" = percentage saturation of the blood with oxygen, and X — the oxygen-pressure to which the blood is exposed. When the P^ of the blood is plotted directly against the negative logarithm of the constant K, it is found that the latter is practically a linear function of the former (Fig. 5). In the experiment just described, the P of Barcroft's blood before ex- ercise was 7*29 and after the exercise 7 "09. Barcroft further 3 34 THE PHYSIOLOGY OF MUSCULAR EXERCISE — L 4 og. K. P// r • — — 8-10 3 2 1 30 9 t -=— — — — — SjOO \ 7-80 \ \ 7-ao \ 7-70 V, 8 7 6 4-5 4. 3 s 760 \ 7-50 ? \ s ^"S \ 7-40 ■^ \ .^ 7-30 ^ 7-20 2 1 ■-^ 710 "■■ -^ '■~v 10 20 »0 40 50 60 70 80 30 100 Fig. 4.— Barcroft-Peters curve. Abscissa = COj pressure in millimetres. -Log.K. 3-8 3-6 3-4 ■ 3-2 3-0 \ V \ \ \ 2-8 9.K s \ s s 24 \ 68 70 7-2 7-4 7-6 7-6 80 82 Fio. 5, — Barcroft-Peters curve (from Hasselbalch) THE REACTION OF THE BLOOD DURING EXERCISE 35 determined that the change in the affinity of his haemoglobin for oxygen, brought about by the exercise, corresponded with that produced by the addition to his blood of sufficient lactic acid to make its percentage in the blood 0'023 per cent. The occurrence of a change of this magnitude in the reaction of the blood during moderate exercise is very difficult to under- stand, in view of Campbell, Douglas, and Hobson's observation that a fall of 0'02 in the ?„ value of the blood increases the pulmonary ventilation by 10 litres a minute. If this is the case, a fall of 0"2 in the Ph of the blood would certainly produce extreme dyspnoea, whereas it is clear from Barcroft's description of his climb that he experienced no respiratory distress. TABLE IX. — Reaction of the Blood During Exercise as Calculated (a) FROM Haldane's Data and (i) from Barcroft's Experiment. (a) Haldane. (6) Barcroft. Rest .... Moderate exercise Severe exercise . C„, Ph. 3 X 10-8 7-52 4-3 X 10-8 7.37 Ch. Ph. S X ID-" 7-29 8 X 10 -» 7-09 The difficulty of reconciling these results is not lessened by Bayliss' observations on the actual change in reaction, produced by the addition of acid to blood, either in vitro or in vivo. Bayliss (19 18) added varying amounts of acid to cat's blood- plasma, this being exposed to a constant tension of carbonic acid (about 40 mm. Hg), so that any change in the reaction of the plasma was due entirely to reduction of the alkali-reserve. He found that the addition of sufficient acid to neutralise half the sodium bicarbonate in the plasma altered its ?„ value from 6"9 to 6-8, an increase of 3 x io~* in its H- ion concentration. The same sample of plasma was then exposed to carbonic acid at a tension of only 20 mm. Hg, with the result that its reaction be- came the same as it had been before the addition of acid. This experiment demonstrates, first, the trivial change in the reaction of the blood produced by a considerable reducfion of its content of sodium bicarbonate, and second, that, when the plasma bicar- bonate and the tension of carbonic acid in the plasma are simul- 3 36 THE PHYSIOLOGY OF MUSCULAR EXERCISE FT ro taneously reduced to half their normal value, the ratio — ? 5-, NaHCOg and, therefore, the reaction of the blood are unchanged. In the normal animal, the sensitiveness of the respiratory centre is such that a very considerable fall in the alkali-reserve of the plasma may be completely counterbalanced by increased pulmonary ventilation, and the reaction of the blood may remain unchanged. Bayliss showed that, when acid was added to the circulating blood, no change in its reaction could be detected when one-third of the bicarbonate in the plasma had been neutralised, since the tension of carbonic acid was simultaneously lowered by increased pul- monary ventilation. The reaction of the blood was determined by means of standard phosphate mixtures, using neutral red as an indicator. This indicator is particularly valuable for estimating the reaction of blood plasma, since it is but little affected by proteins and salts, and it changes colour when the H' ion concentration is just above or below the normal reaction of the blood (Sorensen, Miss Homer). Barcroft calculated that the amount of lactic acid added to his blood, during his climb of i,ooo feet, was such that it then contained 0*023 per cent, lactic acid. Bayliss finds that this amount of acid, if added to blood-plasma, combines with only one-eighth of the sodium bicarbonate in plasma, and that the change in the reaction of the blood, thereby produced, is imper- ceptible. The evidence brought forward by Bayliss suggests that the effect of exercise upon the reaction of the blood cannot have been so large as Barcroft's experiments led him to suppose. The method usually adopted by Barcroft for ascertaining the amount of lactic acid present in blood was that originally devised by Mathison. It consists essentially in determining the amount of acid which must be added to normal blood in order to render its dissociation curve identical with that of the blood under examination ; both samples of blood are exposed to a con- stant tension of carbonic acid. Since the tension of carbonic acid is kept constant, it is clear that Mathison' s method merely measures the alkali-reserve of the blood and gives very little indication of the H" ion concentration of the blood while yet in circulation. Further, it has been observed by Hasselbalch (19 17) that the relation between the P„ of the blood and the negative logarithm of the constant K in the formula -^ = — does not hold 100 I + K THE REACTlbN OF THE BLOOD DURING EXERCISE 37 good for all individuals ; and, under some pathological conditions, his results showed considerable deviation from the linedr relation- ship represented in the Barcroft-Peters curve. A similar devia- tion was observed by T. R. Parsons and W. Parsons, in conjunction with myself, in a single experiment on the effects of exercise upon the reaction of the blood, Barcroft's method showing a greater rise in the C„ of the blood than did the gas electrode. The occurrence of this deviation at once suggests that the key to the difference between Barcroft's results and those calculated from Haldane's data as to the reaction of the blood during exercise is to be found in the fact that Barcroft's method measures the reaction of the red cells, whereas the activity of the respiratory centre depends on the C„ of the plasma. Whi e, in the resting individual, the red cells and the plasma are presumably in equilibrium, it seems possible, as J. W. Trevan ^ has suggested, that, owing to the interchange of acid and basic radicles between the red cells and plasma during exercise, the C„ of the red cells may increase more than does that of the plasma. The" occurrence of such a change would account for the divergence between Barcroft's results and calculations based on Haldane's data. Again, as Barcroft and Camis (1909) have shown, the affinity of haemoglobin for oxygen is influenced, not only by the reaction of the blood, but also by other factors and notably by electrolytes. It is conceivable, therefore, that during exercise changes may take place in the character of the salts in the red cells, and that these may disturb the normal resting relationship between the reaction of the blood and the constant K. There is no clear evidence, however, of such changes, and the actual alteration in the reaction of the arterial blood during exercise still awaits investigation, though it is probable that, partly owing to the efficiency of the respiratory centre, and partly as the result of the stabilising influence of the red corpuscles and of the tissues, this alteration is extremely small. Whatever may be the extent to which it occurs, the change in the reaction of the blood during exercise must be effected, either by a rise in the tension of carbonic acid in the blood, or by a diminution of its alkali-reserve, or by a combination of these two processes. The active muscles produce both lactic and ' Private communication. 38 THE PHYSIOLOGY OF MUSCULAR EXERCISE carboriic acids, though, if the exercise is gentle, the lactic acid is ap- parently completely oxidised in the muscles, and the rise in the Ch of the blood is due solely to a rise in the tension of carbonic acid in the blood. During vigorous exercise some lactic acid escapes oxidation and passes into the blood, and Ryffel (1909) showed, by direct analysis, that, after severe exercise, the blood may contain as much as 0*07 per cent, lactic acid. The acid, by reacting with the plasma bicarbonate, lessens the alkali-reserve of the blood and at the same time sets free carbonic acid. Vigorous exer- H CO cise, therefore, alters the ratio — — |— — 3-, and increases the C„ iN 3. XT. v^ ^-'3 of the blood, and, consequently, the pulmonary ventilation, not only by raising the tension of carbonic acid, but also by lessening the bicarbonate in the plasma. After the exercise is over, the hyperpncea continues until suf- ficient carbonic acid is removed from the blood to bring back fT r*o the ratio ^^ ^.^ J, , that is to say, the reaction of the blood, to its NaHCOj normal value ; and, if the passage of lactic acid into the blood has lessened the bicarbonate content of the plasma, this can only be effected by a corresponding fall in the tension of carbonic acid in the blood (and alveolar air). Hence a low alveolar tension of carbonic acid, shortly after exercise, not only indicates that lactic acid has passed into the blood, but is to some extent a measure of the extent to which this has occurred ; and Haldane and Douglas (1909) have demonstrated that after vigorous exertion, a considerable fall may take place in the alveolar tension of car- bonic acid. TABLE X. — (Douglas and Haldane.) Nature of Exercise. Tension of Carbonic Acid in Alveolar Air. Rest. During Exercise. After Exercise. (i) C.G.D. walking 600 yds. at 5 miles per hour (2) C.G.D. walking 600 yds. at 6 miles per hour (3) C.G.D. running 300 yds. in 52 seconds 3975 mm. Hg 3975 mm. Hg 39-50 mm. Hg 45-4 44-5 ~ 10 mins. later, 39-6 15 ,. „ 36-8 25 » ,. 34'i THE REACTION OF THE BLOOD DURING EXERCISE 3^ The Significance of Lactic Acid in the Blood During Exercise. If the concentration of lactic acid in the skeletal muscles increases, some of the acid diffuses into the blood ; and the pres- ence of lactic acid in greater amount in the blood during exercise implies that lactic acid is being formed in the muscles more rapidly than it can be oxidised. The rate at which lactic acid is produced almost certainly varies directly with the activity of the muscles ; the rate of its oxidative removal depends upon the ability of the oxidative mechanism in muscle to effect its oxida- tion, and upon the presence of an adequate supply of oxygen for this purpose. It is not difficult to imagine that, even though the supply of oxygen is ample, the oxidative mechanism may be unable to deal immediately with the whole of the lactic acid presented to it during severe exercise. The nature of this mechanism is un- known, but, presumably, it is due to some catalytic process into which the factor of time must enter. However efficient the oxi- dative mechanism may be, the oxidation of lactic acid cannot be instantaneous, and, assuming that the rate at which lactic acid can be oxidised is a limiting factor, it is quite conceivable that the rate of production of lactic acid may outstrip the rate at which it is oxidised; and the excess will pass into the blood. If this view is correct, the process would be comparable with the hyperglycaemia which occurs, when the ability of the liver to form glycogen is overtaxed by the sudden entrance of an excess of glucose into the portal circulation. The usually accepted view, however, is that the presence of lactic acid in the blood during exercise is the result of an inade- quate supply of oxygen to the active muscles. It appears to have originated as the outcome of the work of Araki (1894), who found lactic acid in the blood of animals in which the oxygen- carrying power had been diminished by the administration of carbon monoxide. Hill and Flack (1909) have brought forward good evidence that very violent exertion may lead to an acute and marked deficiency in the supply of oxygen to the body ; and Barcroft and his co-workers (1915) observed that a combination of exercise with an inadequate supply of oxygen, namely, exercise at a high altitude and in unacclimatised individuals, caused a large increase in the amount of lactic acid in the 40 THE PHYSIOLOGY OF MUSCULAR EXERCISE blood. It seems clear, therefore, not only that lack of oxygen niay occur during exercise, but that it may be sufficient to inter- fere with the normal oxidation of lactic acid ; in these circum- stances lactic acid will undoubtedly enter the blood in larger amount But the point at issue is not whether an acute and unmistak- able lack of oxygen may cause the accumulation of lactic acid in muscle and its passage into the blood, but whether the appear- ance during moderate exercise of a small amount of lactic acid in the blood has' necessarily the same significance. The evidence that this is the case is by no means convincing. Barcroft found that half an hour's walk, which entailed " no sort of respiratory distress," increased appreciably the amount of lactic acid in his blood ; and, if this were the result of lack of oxygen, it would be necessary to believe that the circulatory and respiratory adjust- ments taking place during exercise fail to fulfil their function, except when the exercise is very gentle. Again, there is a considerable body of evidence that a moder- ate lack of oxygen, unless this is prolonged, does not lead to the appearance of lactic acid in the blood. Ryffel (1909) found that, even when the percentage of oxygen in alveolar air was reduced to 4 per cent, for fifteen minutes, the amount of lactic acid in the blood was unchanged. In another experiment, he spent three hours and twenty minutes in a respiration chamber, in which the tension of oxygen was gradually lowered. At the end of the ex- periment, his alveolar aircontained 4-15 per cent, of oxygen, but there was no increase in the lactic acid in his blood. The per- centage of lactic acid rose only when experiments of this kind were prolonged for four hours or more. Since lactic acid may pass into the blood during exercise under conditions which appear to preclude an inadequate supply of oxygen, and since, on the contrary, a considerable deficiency in oxygen-supply does not necessarily raise the percentage of lactic acid, the appearance of lactic acid in the blood during moderate exercise hardly warrants the conclusion that the oxygen- supply to the active muscles is necessarily inadequate. Although the available evidence scarcely justifies a decision as to the significance of the appearance of lactic acid in the blood during moderate exercise, the conception that it represents merely a lag in the working capacity of the oxi- SUMMARY 41 dative mechanism, as compared with the production of lactic acid, is at least as reasonable as the view that a shortage of oxygen-supply exists during moderate exercise in a healthy man. Summary. The oxygen-consumption of the body per minute during exercise varies almost directly with the amount of external work performed, and an equally close relationship qxists between the pulmonary ventilation and the oxygen-consumption of the body. The greater pulmonary ventilation during exercise is due, partly to a rise in the H" ion concentration of the blood, and, probably, partly to a greater sensitiveness of the respiratory centre to this stimulus, the latter being brought about by an outflow of im- pulses from the higher centres to the respiratory centre concom- itantly with the passage of impulses from the cerebral cortex to the skeletal muscles. Since both the H- ion concentration of the blood and the excitability of the respiratory centre probably increase part passu with the severity of the muscular work, the correspondence between the pulmonary ventilation and the amount of muscular work can be adequately explained. The H* ion concentration of the blood is represented by the HjCO, expression K -^ hCO ' ^h^'^^ HjCOg is proportional to the tension of carbonic acid in the blood, NaHCOj is the amount of sodium bicarbonate in the plasma, and K is the dissociation constant of H,C03. During exercise the H* ion concentration of the arterial blood is increased, not only by a rise in the tension of carbonic acid in the blood but also usually by a decrease in the bicarbonate of the plasma, this being caused by the passage of lactic acid into the blood. The efficiency of the respiratory centre is such that the tension of carbonic acid does not rise greatly, and the exchange of acid and basic radicles between the blbod-plasma and the red cells and the tissues probably prevents any serious decrease in the bicarbonate of the plasma. As a result of these regulating processes, the reaction of the arterial blood alters very slightly during exercise. The suggestion is put forward that the appearance of lactic 42 THE PHYSIOLOGY OF MUSCULAR EXERCISE acid in the blood during moderate exercise does not necessarily indicate an inadequate supply of oxygen to the muscles, but that it may merely represent a discrepancy between the rate at which lactic acid is produced and the rate at which it can be oxidised by the muscles. CHAPTER IV. THE OUTPUT OF THE HEART DURING EXERCISE. The Diastolic Filling of the Heart. The Output per Beat. The Size of the Heart During Exercise. In order that the greater pulmonary ventilation during exercise may contribute effectively to meeting the requirements of the body for oxygen, two conditions must be fulfilled. In the first place, the arterial blood leaving the lungs must be as fully, or almost as fully, saturated with oxygen as during rest. In the second place, the rate of the blood-flow round the body as a whole (the circulation rate) must correspond with the degree of pulmonary ventilation. Assuming for the moment that the first condition is fulfilled, it is clear that the closer the correlation between the pulmonary ventilation and the circulation rate, the more efficiently will the respiratory and circulatory systems carry out their func- tion of providing in the lungs, and transporting to the tissues, the oxygen needed during exercise. Greater pulmonary ventila- tion, for example, if unaccompanied by a more rapid circulation rate, would scarcely alter the amount of oxygen reaching the tissues in a given time. That, during exercise, a definite relationship does exist, not merely between the pulmonary ventilation and the circulation rate but also between these two processes and the amount of muscular work performed, is shown in Fig. 6. But, before enter- ing on a discussion of the question as to how this relationship is brought about, it is necessary to consider the factors which regulate the circulation rate. The rate of the blood-flow round the body as a whole depends entirely upon the output of the heart per minute, and the other circulatory adjustments, occurring during exercise, are of value chiefly in that they enable the out- put of the heart to be utilised to the greatest advantage in sup- plying blood to the active organs. 43 44 THE PHYSIOLOGY OF MUSCULAR EXERCISE The Output of the Heart. Although the earlier observations of Loewy and v. Schrotter (1905) and of Plesch (1909) suggested that the output of the heart in man was increased by muscular wprk, the methods which they Liters 16.00 14.70 13.40 •2.10 — 1 r- -1 1 r- / ,y Liters 26 Kg.Meters 105 210 315 420 525 630 735 • 840 945 1050 Worl( per Minute Fig. 6. — (Means and Newburgh.) BF = circulation rate (blood-flow). V = pulmonary ventilation. Oj = oxygen consumption. adopted were so indirect that their results were inconstant and of rather doubtful value. Plesch calculated, for example, that during exercise the output of the heart jtnight reach the almost incredibly high figure of 45 litres per minute. The first really accurate observations on the output of the heart in man were made by Krogh (1912), who employed, in a greatly improved THE OUTPUT OF THE HEART DURING EXERCISE 45 form, the nitrous oxide method first devised by Zuntz, MarkofF, and Miiller (191 1). Its trustworthiness has been confirmed by Boothby (1915) and by Lindhard (191 5), and the latter has improved it in some respects. The method has been criticised by Sonne (19 18), who points out that two conditions are essential for its successful application. It is necessary, first, that the nitrous oxide should be uniformly mixed with the other gases in the lungs, and secondly, that, during its passage through the lungs, the blood should take up sufficient nitrous oxide to come into equilibrium with the tension of nitrous oxide in the alveolar air. According to Sonne neither of these conditions is fulfilled. He finds that the first error gives an oxygen absorption which is too low, and the second an oxygen absorption which is too high, although, since the two errors tend to neutralise one another, the actual results obtained by Krogh and Lindhard may often be approximately correct. Krogh and Lindhard appear, however, to have taken adequate precautions to avoid serious error from the first of these causes ; and the great solubility of nitrous oxide must reduce the second possibility of error to a minimum. The application of this method has shown that the output of the heart varies from 3 to S litres per minute in the resting individual, that it is raised by moderate work to 8 or 9 litres, and that during heavy muscular work it may reach 20 litres or even more. Using a different method, Christiansen, iDouglas, and Haldane (191 4) obtained in resting subjects an output of 6 litres per minute. Taking the oxygen-consumption of the body as a measure of its metabolic activity. Means and Newburgh (191 5), Boothby (191 5), and Lindhard (191 5) further find that the output of the heart per minute runs practically parallel with the consumption of oxygen (Fig. 6) ; and, since the increased consumption of oxygen during exercise takes place mainly in the active muscles, including the heart, it is for practical purposes a measure of the work done by the body. In some of Lindhard's, and of Means' and Newburgh's, experiments the external work, which consisted in pedalling a bicycle ergometer, was measured, and an almost linear relationship was observed between the work performed and the output of the heart (Fig. 7). 46 THE PHYSIOLOGY OF MUSCULAR EXERCISE TABLE XI. — Rblation of Oxyoen-Consumption to the Qutput of the Heart. (From Lindhard's Data.) Oxygen-Consumption Output per Minute Pulse-Rate per Minute in c.c. in Litres. per Minute. Rest 330 4'9 1 72 Work . 606 6-3 86 „ . . ,. I171 M75 92 11 ■ • •* 1759 16-65 128 1880 i8-5 130 2407 22-6 148 2750 28-6 The highest figures in Table XI. must represent almost the 25 ^20 X X ^ X y- c x^' 1f 10 X X y^ <•- y ^ 5 3 a. 3 1 1 1 1 1 1 1 100 200 300 400 500 600 700 800 900 1000 liOO 1200 1300 140 Work done : kilogrammetres per minute. Fio. 7. — (Constructed from Lindhard's data.) maximal output of which the heart is capable, even in a powerful and highly trained man ; and it is probable that, in the average man, the maximal output per minute does not often exceed 1 5 or 16 litres. Since the heart cannot discharge during systole (except for a few beats) more blood than it receives during diastole, the diastolic filling of the heart must be similarly in- creased during exercise. The Diastolic Filling of the Heart. Apart from the duration of systole, the only two processes which can affect the diastolic filling of the heart are, first the THE DIASTOLIC FILLING OF THE HEART 47 venous pressure, and second, the rate and completeness of the relaxation of the muscular walls of the ventricles. Since all the evidence shows that the conditions on the two sides of the heart are normally identical, it will be sufficient to consider only the right side of the heart. Tone. — The idea that the heart muscle possesses tone, using this term to mean that the walls of the auricles and ventricles do not become completely relaxed and flaccid during diastole, originated from Gaskell (i 880-1 882), who found that perfusion of the frog's ventricle with alkaline saline solution led to less complete relaxation between the beats of the ventricle and finally to standstill in systole, whereas acid solutions brought about the converse effect, namely, diastolic standstill. This view appears to be generally accepted, as regards the human heart, by clinical writers (Clifford Allbutt, Mackenzie), and it has been adopted by Yandell Henderson (1909), who believes, not only that the heart muscle possesses diastolic tone in the sense that its relaxa- tion is not necessarily complete, but also that this tone is variable, and that, under a given venous pressure, the distensibility of the ventricles, and hence the filling of the heart, is not always the same. This belief rests, in part, upon the observations (Y. Hen- derson) that excessive pulmonary ventilation leads to very imperfect filling of the heart, and that, on the contrary, deficient pulmonary ventilation brings about dilatation of the heart. Jane- way and Ewing(i9i4), however, have brought forward evidence that excessive pulmonary ventilation (with the chest open) lessens the filling of the heart by mechanically interfering with the return of blood to the heart ; and Piper, Patterson, and Starling (19 14), have shown that lack of oxygen causes the heart to dilate, in accordance with the law of the heart, in order to compensate for its decreased contractile power. They found no evidence of varying distensibility of the heart during diastole under a con- stant venous pressure ; on the contrary, the filling of the heart was determined solely by the venous inflow. In Yandell Henderson's experiments, an increase in venous pressure did not appreciably alter the curve of diastolic filling of the heart, and he believes this to be due to a compensatory rise of diastolic tone. Krogh (1912) has suggested in explanation of this result that the venous inflow was already so large that 48 THE PHYSIOLOGY OF MUSCULAR EXERCISE a further increase in venous pressure made but little difference to the rate of filling of the heart ; and the similarity between Henderson's and Barringer's curves (Fig. 1 1) and those obtained by Patterson, Piper, and Starling (Fig. 1 2) under a large venous inflow renders Krogh's suggestion very probable. It is possible, therefore, to interpret Henderson's results without invoking diastolic tone. Further, even when the experimental conditions are apparently similar to those in Henderson's experiments, a rise in venous pressure may increase the rate of filling and the output of the heart per beat, even though the pulse-rate at the same time becomes more rapid (Bainbridge, 191 5). Nor do Gaskell's observations necessarily imply the existence of diastolic tone, since they can be equally well explained by assuming that alkali prolongs the systolic phase and cuts short the period of diastole, whereas acid has the converse action. The balance of evidence, therefore, is against the existence of diastolic tone, even in the normal heart, and the conclusion appears unavoid- able that the heart muscle is normally completely relaxed during diastole, and that its filling is determined entirely by the venous inflow. The Venous Inflow. The most important means concerned in increasing the venous inflow to the heart, and consequently its output, during exercise is undoubtedly the movements of the skeletal muscles. Tigerstedt (1909) has shown that tetanisation of the hind limbs, after section of the spinal cord in the lumbar region, brings about a larger output of the heart, as the result of a greater venous inflow ; and this he regards as due to the mechanical action of the muscular movement on the return of blood to the heart. The importance of such movement in promoting the return of blood to the heart, by mechanically squeezing blood out of the veins of the muscles into the great veins, has been emphasised by Leonard Hill (1908) ; and the more vigorous the muscular movement, and the larger the number of muscles employed, the greater must be their effect upon the return of blood to the heart. Indeed it seems very probable that the increased rate at which blood reaches the heart during exercise varies almost directly with the amount of muscular movement. In this way, the muscles act as a subsidiary pump, and the combined action of the heart in driving blood into the THE Diastolic filling of the heart 49 vessels of the muscles, and of the active muscles in sending blood back to the heart, must greatly increase its output per beat. It is clear that the muscles can act in this way only if blood enters the vessels of the muscles from the arterial side as rapidly as it is forced out of these vessels into the great veins. The constriction of the splanchnic vessels, which occurs at the very outset of exercise, immediately diverts a large volume of blood into the muscles, and raises the pressure at which it is sent into their blood-vessels. The greater flow of blood into the active muscles, thus brought about, allows them at once to send more blood into the great veins, and thence to the heart. But the output of the heart does not increase during exercise, as Krogh has shown, until sufficient time has elapsed for this to take place. Hence the machinery, by which the output of the heart increases during exercise, is set, in motion by the purely mechani- cal action of the active muscles, and in this manner the blood-flow to the muscles, at least so far as this depends upon the output of the heart, is very largely determined by their own activity. Dilatation, of the blood-vessels in the muscles, in so far as it occurs during exercise, will allow still more blood to enter these vessels in a given time, and will thereby enhance the return of blood to the heart. It is generally believed that the respiratory movements sup- plement the action of the skeletal muscles in this respect, and there seems to be no doubt that the movements of the diaphragm, by raising the intra-abdominal pressure and squeezing blood out of the vena cava, do increase the flow of blood to the heart. The extent to which costal respiration acts in this way is a matter of controversy. Y. Henderson found that more vigorous respira- tion had little or no effect on the filling of the heart, a result which is not surprising since (in his experiments) the venous in- flow was already very large. Lewis (1908) showed that, in man, a pure costal inspiration lowers the arterial pressure, presumably by lessening the venous inflow, whereas abdominal respiration raises the pressure, and the actual effect of respiration upon the flow of blood to the heart therefore varies with the type of breath- ing. During short spells of violent exertion, the breathing is both costal and abdominal, and its effect upon the venous inflow is per- haps not very large. But, during prolonged steady exercise, such as a cross-country run, the breathing is chiefly abdominal (L. Hill), 4 5o THE PHYSIOLOGY OF MUSCULAR EXERCISE and the respiratory movements must be of great importance in assisting the diastolic filling of the heart. I Krogh (1912) has suggested that the portal system also plays a considerable part in increasing the blood-flow to the heart during exercise. He regards the portal mechanism as consisting of two resistances, the first being the intestinal arterioles, and the second the portal vein and its tributaries ; between these two resistances, the intestinal capillaries form a rather large reservoir. His view appears to be that stimulation of the splanchnic nerves, assuming it to cause, at the same time, contraction of the intes- tinal arterioles, dilatation of the capillaries of the liver, and contraction of the portal vein, will drive into the great veins more blood than could be driven out by contraction of the intes- tinal arterioles alone, since the contraction of the arterioles lessens the flow into the portal system, which therefore contracts and discharges blood into the central veins. The observations of Bainbridge and Trevan (1917), however, are not in favour of this view. They have shown that stimulation of a splanchnic nerve, or the injection of adrenalin, gives rise to some obstruction to the flow of blood from the liver into the general circulation, and, although the portal pressure rises, the pressure in the vena cava shows little or no alteration. It does not appear probable, therefore, that the portal mechanism can take any great share in increasing the flow of blood to the heart. The efficiency of the muscular and respiratory movements, in increasing the venous inflow during exercise, is demonstrated by the fact that the venous pressure rises considerably (Hooker, 191 1). Such a rise indicates that the venous inflow is sufficient, not merely to increase the output of the heart, but also to provide a head of pressure which ensures rapid filling of the heart during diastole. The Factors which Determine the Output of the Heart. The heart possesses two means of increasing its output per minute in response to the greater inflow of blood during exercise : these are a larger output per beat and acceleration of the pulse- rate. According to Boothby's observations (191 5), the increased output per minute is eff"ected almost entirely by a rise in the pulse-rate ; . and he finds that the pulse-rate, like the output per THE DIASTOLIC FILLING OF THE HEART 51 minute, has practically a linear relation to the oxygen-consump- tion (Fig. 8), and therefore to the intensity of the muscular work. In his experiments, the alternative method of increasing the out- put of the heart per minute (often termed the minute-volume), namely, a larger output per beat, plays a very small part, and. F~ — . — " "~ ,i^ i-.t! J^ <■ ^ X y y y y y 1/ ' a jl y V t^ y ^ y y ^ y ^ y^ y ^ f ^ ^ y t^ X ^ ^ ^ y • ^ ^ y ^ y y r-r- *> / ti -^ ^ ^ ■^ V ..V ^ ^ ' ^ ^ \v^ \ '' ° i^ < ^ <1 i * ^ ^^ iJl * A Ol Ct.l^ iy. un V „*■ "^ .^■^ \x ? M V r« M Fio. 8.— (Boothby.) even when the consumption of oxygen is increased threefold, the output per beat only rises 8-5 c.c. Boothby's observations were made on a single individual, and Krogh and Lindhard, who have studied the eiTects of exercise in a number of individuals, conclude that the relationship between the pulse-rate and oxygen-consump- tion is by no means so constant as Boothby supposed, and that it may even vary in the same individual at different times. They 52 THE PHYSIOLOGY OF MUSCULAR EXERCISE found that, in highly trained men, the increase in the minute- volume of the heart during moderate exercise was obtained to a much greater extent by increase in the output per beat, and to a much smaller extent by acceleration of the .pulse, than in the un- trained person. They showed that, if the consumption of oxygen is the same in the two cases, the trained man almost invariably has a less frequent pulse than the untrained man. This is brought out by the following figures, obtained respect- ively from two trained athletes (J. J., and J. L.), and from two less highly trained individuals (W. M. B. and Frau M.). TABLE XII. — (From Lindhard's and from Boothby's Figures.) Subject. O2 Consumption c.c. per Minute. Minute-Volume jf Heart in Litres. Output of Heart per Beat in c.c. Pulse-Rate. Traimd. (i) J. L. Resting . Working . (2) J. J. Resting . Working . 2ig 782 330 797 3-9 9-0 4-9 ii-o 59 100 72 127-5 66 90 68' 86 Untrained. (3) W. M. B. Resting . Working . (4) Frau M. Resting Working{g 185 912 195 927 1070 3 '57 9-31 4-2 975 107 61-5 70 69-5 8i-o 71 -0 58 133 61 t20 150 The figures given in this table by no means represent the maximum output of the heart per beat. Lindhard's observations show that, in severe exercise, the output per beat may be as much as 1 50 to 160 c.c. ; in one of his experiments the output per beat, which during rest was 69 cc, was raised to 150 c.c. during heavy work, the pulse-rate at the same time increasing from 71 to 118 per minute. Means and Newburgh have recorded an output of 164 cc. per beat, the pulse-rate being 107, and the con- sumption of oxygen being 1640 cc. per minute. That the pulse-rate does not always correspond with the severity of the exercise is also very evident from the observations of Means and Newburgh (Fig. 9). In the experiment illustrated in this figure, the pulse-rate (after an initial acceleration) remained lioT^ time almost steady, although the amount of work performed THE DIASTOLIC FILLING OF THE HEART S3 in a given time was steadily becoming larger, and the increased output of the heart per minute was effected entirely by a pro- gressively larger output per beat. It may be concluded, then, that, in different individuals, during moderate exercise, the in- creased output of the heart per minute may be brought about either by a larger output per beat and a slight acceleration of the pulse or by acceleration of the pulse with little or no increase in the output per beat, and that every gradation may exist be- tween these two extremes. ex. — [ — — I — 1 — 1 — 1 1 ' 130 ( /■ 120 z^"' y /. / 110 c ) 100 '/ -—"^ ■ / / 90 "/ / / / / ■ 80 -/ / . // j i ._P_. 70 / / ■ / ' c ) 60 r f 1 1 1 — . 1 — . I — J Kg.Meters 270 315 420 525 630 735 Work per Minute 84-0 945 50 .45. 1050 Fig. g. — (Means and Newburgh.) P = pulse-rate. VPB = output of heart per beat. C = coefficient of utilisation. Before discussing the significance of the difference in the re- sponse of the heart in different individuals, it will be convenient to consider briefly the factors which determine first, the power of the heart to increase its output per beat, and second, the in- fluence of the pulse-rate upon the output per minute. The Output of the Heart per Beat. Patterson, Piper, and Starling (19 14) have recently proved that cardiac muscle resembles skeletal muscle in that the energy 54 THE PHYSIOLOGY OF MUSCULAR EXERCISE set free when it contracts, and therefore the force with which it contracts, is directly proportional to the initial length of its fibres ; the phrase, initial length, means the length of the fibres just before they begin to contract. Since the heart is a hollow organ, the initial length of its fibres will vary directly with its volume at the end of diastole; consequently, the diastolic volume of the heart determines the energy set free, that is to say, the force with which the heart muscle contracts, during the following systole. Upon this fundamental principle, which Starling has termed " the law of the heart," depertds the ability of the heart to increase its output in response to a larger venous inflow of blood into the heart, and to maintain its output in the face of a raised arterial pressure. Theoretically, one might suppose that, when the venous inflow becomes larger, the greater diastolic filling of the heart would increase its contractile power to such an extent that it would, at the next systole, discharge into the arterial system all the blood entering it during the preceding diastole, and that its systolic volume would not alter. This is the case for the heart of the tortoise in which, as Kozawa (191 5) has shown, the ad- aptation to increased filling of the. heart is perfect, and the law of the heart is absolutely obeyed. But Patterson, Piper, and Starling find that, at least under experimental conditions, this is not perfectly true for the mammalian, heart. If the venous inflow becomes larger the output of the heart increases, but for a few beats the output does not keep pace with the inflow. The result is that the diastolic (and systolic) volume of the heart gradually becomes larger, and there is a concomitant increase in the force with which the heart contracts at each successive systole. After a short time the diastolic volume, and, therefore, the contractile power of the heart, become so large that the output of the heart equals the in- flow, while its volume at the end of systole has been increased (Fig. 10). The heart reacts in precisely the same way to a rise of arterial pressure, and, after a few beats, it becomes dilated to such an extent that it is able to maintain the same output against the higher pressure as that existing before the rise of pressure took place. Dilatation of the heart, therefore, is an essential part of the mechanism by which it can increase or maintain its output in response to a greater venous inflow or to a higher arterial pres- THE DIASTOLIC FILLING OF THE HEART 55 sure. It is a perfectly normal process, and the extent to which it can take place, under physiological conditions, is ultimately limited by the pericardium. Fig. 10. — Effect of alteration in venous supply on volume of isolated heart. (Patterson, Piper, and Starling.) B.P. V.P. Rale. O.P. O.P. per Beat Calc. O.P. per Beat Observed. A. 124 B. 130 C. 122 95 22 86 3-g 57 145 22 140 6'4 8'o 55 22 33 1-5 2-5 BP = arterial pressure. VP = pressure in vena cava close to the heart in mm. water. OP = output of heart in c.c. per 10 seconds. Rate '= number of beats in 10 seconds. C = cardiometer tracing of the volume of the heart. The Contractile Power of the Heart. Although every heart obeys the law just described, the actual amount of energy set free during each beat, or, in other words, the contractile power of the heart for any given diastolic volume, varies with the nutritive condition of its muscular fibres. Assum- ing its diastolic volume to remain constant, a well-nourished heart 56 THE PHYSIOLOGY OF MUSCULAR EXERCISE will contract more strongly and will set free more energy than a badly-nourished heart ; and Patterson, Piper, and Starling use the term " tone " to indicate the physiological fitness of the muscle fibres, this being the outcome of their nutritive condition and being manifested by their ability to develop energy. Tone, therdbre, means greater force of contraction during systole, not lessened re- laxation during diastole. It follows that, for any given increase in the length of its fibres, that is to say, in its diastolic volume, the contractile power of a well-nourished heart will increase more than that of a heart whose nutrition is impaired, and that, if the contractile power of the two hearts is to be the same, the badly- nourished heart must dilate more than a normal one. Patterson, Piper, and Starling have shown that this is the case, and that, in order to increase its output in response to a larger venous inflow, a heart, which is fatigued or badly nourished, must dilate much more than does a normal heart. It is clear, therefore, that the diastolic volume of the heart does not necessarily give any in- dication of its output per beat. Another condition which must influence the extent to which the heart dilates, as the venous inflow increases or the arterial pressure rises, is the size of its musculature. A thick-walled ventricle will obviously be in a favourable position as compared with a thin ventricle, since the larger the number of fibres the greater will be the cumulative effect of a trivial increase in their length upon the contractile power of the heart ; hence a thick- walled ventricle can increase its output with much less dilatation than can one whose walls are thin. Although Barnard ( 1 898) long ago pointed out that the primary function of the pericardium is to prevent over-distension of the heart, the idea that this function might be exercised in the ordinary course of daily life has never obtained general currency. The actual capacity of the pericardial sac, after deducting the space occupied by the heart-muscle, has been investigated by Hender- son and Prince (19 14), who found that it varied in different individuals from 450 to 600 c.c. Assuming that each ventricle is capable of holding a third of the total blood in the heart, they calculate that each ventricle can contain from 1 50 to 200 c.c, when the heart completely fills the pericardium ; in one case, a very muscular man of nineteen years, the capacity of the left ventricle amounted to 230 cc. Since the output of the left THE DIASTOLIC FILLING OF THE HEART 57 ventricle per beat rarely exceeds 150 c.c, Henderson and Prince concluded that the heart never dilates sufficiently to fill the peri- cardium. But they overlooked the fact that, as its output in- creases, the systolic as well as the diastolic volume of the heart becomes larger (Fig. 10), and that, in order to maintain an output of 1 50 c.c. per beat, the volume of each ventricle at the end of systole may easily be such that it contains 50 or 60 c.c. of blood ; in that case its content of blood at the end of diastole might well be over 200 c.c, and the heart as a whole would completely fill the pericardial sac. Further, the less the contractile power of the heart-muscle the greater is the extent to which it must dilate in order to produce a given increase in output, and, therefore, the larger will be its residual content of blood at the end of systole. A feeble heart might, therefore, completely fill the pericardial sac, even though its output per beat was not greatly increased. The Output per Beat During Exercise. The difference in the behaviour of the heart in different in- dividuals, as regards its output per beat, can be readily accounted for along these lines. It is easy to understand that the powerful heart of the athlete, while obeying the law of the heart, is able to Tespond to a moderate increase of venous inflow by a much larger output /er beat, whereas the smaller heart of the sedentary person, even if dilated to its physiological limit, can only moderately increase its output per beat. This is the true explanation of the difference in the so-called reserve-power of the heart in different individuals. The calling up of the reserve is effected in accord- ance with the law of the heart, but the extent of the available reserve is determined by the contractile power of the heart, this de- pending partly upon itssize and partly upon its nutritive condition ; since the latter are the variable factors, it is upon them that the varied response of the heart to exercise depends in different in- dividuals. A further consequence of the greater dilatation necessary in order that the heart of a sedentary person may increase its output per beat, is that such a heart may dilate nearly to its physiological limit with very little increase in output per beat, and with only a moderate rise in venous inflow. As soon as this point is reached its ability further to increase its minute-volume depends S8 THE PHYSIOLOGY OF MUSCULAR EXERCISE solely on acceleration of the pulse-rate. Hence, in such an in- dividual, increase in minute-volume is obtained, and must be obtained, almost entirely by acceleration of the pulse. On the contrary, the powerful heart of the athlete, with its greater reserve power, can double or more than double its output per beat before reaching its physiological limit of size. This doubtless explains the variation, shown in Table XIL, in the behaviour of the heart in different individuals as regards the output per beat during moderate exercise. The Size of the Heart During Exercise. We should expect from the foregoing argument that severe exercise, and, in an untrained man, even moderate exercise, must considerably increase the diastolic volume of the heart ; and it is almost certain that, in some of the examples just quoted, the heart dilated nearly up to the limits allowed by the pericardium. During recent years, however, the view has gained ground, and is now widely held, that in the healthy person the diastolic volume of the heart does not become larger during exercise. A necessary corollary to this view is that the output of the heart per beat is , not greatly increased during exercise. It rests upon evidence which at first sight appears unimpeach- able, namely, direct measurement of the size of the heart, just before and after exercise, by means of the orthodiagraph or the teleo- Rontgen rays. Using the orthodiagraph Moritz ( 1 908), Hoffmann (1902), and de la Camp (1903 to 1904) found that, in normal per- sons, severe exercise, even when carried to the point of exhaustion, produced no dilatation of the heart, and that sometimes its volume was actually diminished. The forms of exercise taken included wrestling, cycling, and work on the ergometer. On the contrary, Schott (1908) came to the conclusion that considerable dilatation occurred in these circumstances* It may be noted that in none of these experiments was the size of the heart observed during the actual exercise, although the record was taken as soon as possible afterwards. With the object of minimising the interyal between the cessation of the exercise and the observation of the size of the heart, Nicolai and Zuntz (19 14), in their experiments, arranged the apparatus so that the Rontgen ray picture could be taken practically during the exercise, the subject merely stopping work for a few seconds during the actual period of exposure for THE SIZE OF THE HEART DURING EXERCISE 59 the photograph. Their results indicated a small increase, amount- ing on an average to 4 mm., in the transverse diameter of the heart during work, and a definite decrease in size shortly after its cessation, the decrease in size , taking place within three seconds of the cessation of exercise. As a result of calculations based upon the normal capacity and transverse diameter of the heart, they , conclude that its output per ' beat is increased during exercise and may reach 150 c.c. The most recent observations are those of Williamson (191 5), who improved the technique by using the teleo-Rontgen method, and who paid considerable attention to the phase of respiration at which the photograph was taken. This is of importance since the position of the diaphragm appreciably affects the apparent size of the heart, and photographs, if they are to be strictly com- parable, should always be taken at the same point in the respira- tory cycle. The photographs were taken just before, and about twenty seconds after, fairly severe exercise. Williamson found that, taking thirty-three normal subjects, the heart diminished in size in twenty-nine cases, dilated in three cases, and in one case remained unaltered in size. In patients with compensated heart, lesions, or in whom the heart was presumably weakened by some general disease, dilatation occurred in twenty-five out of fifty-seven cases. The average dilatation, when it occurred, Wcis 4 mm. Although Williamson appears to regard an increase of 4 mm. in the transverse diameter of the heart as trivial, the diastolic volume of the resting heart may exceed its systolic volume by about this figure. That is to say the entrance of, on an average, 120 c.c. of blood into the two ventricles leads to quite a small change in its transverse diameter ; and, since the heart is roughly spherical, a considerable addition to its content of blood at the end of diastole would produce a com- paratively slight increase in its diameter. It is probable, in fact, that the presence of an additional 20 or 30 c.c. in the heart at the end of diastole could not be detected by observing it with the Rontgen rays. In some of Lindhard's experiments, however, the amount of blood present in the two ventricles at the end of diastole during exercise must have exceeded their diastolic content of blood during rest by 120 to 180 c.c, a difference which could hardly escape notice. The explanation of the divergence between the results of 6o THE PHYSIOLOGY OF MUSCULAR EXERCISE Krogh and Lindhard and the evidence derived from direct observation of the heart by Rontgen rays lies in the fact that de la Camp, Williamson, and even Nicolai and Zuntz, measured the size of the heart not during but after exercise. Immediately on the cessation of exercise the venous inflow to the heart diminishes owing to the stoppage of the pumping action of the skeletal muscles, while the pulse-rate falls very slowly for at least half a minute, and consequently, for a few beats, the output of the heart exceeds the venous inflow. The heart, therefore, begins to diminish in size almost instantly after the exercise stops, its diastolic volume falling to normal within three or four seconds(Nicolai and Zuntz) ; and if its rate declines slowly, its output per beat and its diastolic volume may for a short time be even less than normal. This sequence of events can be directly observed under experimental conditions. Patterson, Piper, and Starling have found that, \yhen the venous inflow to the heart decreases, its output and diastolic volume reach a lower equilibrium point in seven or eight beats. It may be concluded that, although orthodiagraphic records of the heart have demonstrated the rapidity with which it decreases in size after exercise, and have incidentally served to show the fallacious nature of the evidence derived from percus- sion and palpitation as to the absolute size of the heart, these records throw very little light on the actual size of the heart during exercise, and do not in the least controvert the evidence of Krogh and Lindhard that the output of the heart per beat may be doubled, or more than doubled, during exercise. The conclusion that the output of the heart can be increased either by a larger output per beat or by acceleration of the pulse, and that a large output per minute depends upon the co-operation of both these factors, is not accepted by Yandell Henderson (1906, igog), who has examined directly the changes in the volume of the heart in situ by the plethysmographic method. Henderson brought forward evi- dence that, under normal conditions, the curve of diastolic filling of the heart is always of the same shape, and that shortening of the diastole merely cuts short the curve of diastolic filling without altering the form of the curve (Fig. 11). This means that the rate at which the heart fills during diastole is always the same, and does not vary with the venous pressure. Hence acceleration of the pulse, by cutting short the filling of the heart, necessarily lessens its output per beat, although, owing to the shape of the curve of diastolic filling, the decrease in output per beat does not (especially at first) fall off proportionately with the increase in pulse-rate. Consequently, acceleration of the pulse does increase to some extent the output of the heart per minute. The two most important deductions which Henderson draws from these observations are, first, that acceleration of the pulse- THE SIZE OF THE HEART DURING EXERCISE 6i rate is the only means by which the output of the heart per minute can be increased, and, second, that the large output per beat and per minute, described by Krogh and Lindhard and others, cannot possibly occur. Henderson at first (igog) believed that the greatest minute-volume of which the heart is capable is less than double that occurring during rest. With such an output it would be impossible for the blood to carry to the tissues all the oxygen which is actually consumed during severe exercise. For example, if the output of the heart per minute were 8 litres, this amount of blood would only carry 1500 to 1600 c.c. of oxygen to the tissues, even if it were completely reduced in its passage through the capillaries, whereas the actual consumption of oxygen under these conditions may be 2500 to 3000 c.c. oxygen per minute. Henderson found it necessary, therefore, to assume that only a fraction of the oxygen taken into the body is transported by the blood to the tissues, and that the remainder is utilised in the lungs themselves for the oxidation of metabolic products of muscular activity, a view which was first put forward by Bohr and Henriques (iSg?). But Evans and Starling (1913) have shown that the oxidation of metabolic products is carried out in the tissues themselves, and that the lungs do not complete the oxida- tion of metabolic products formed elsewhere in the body. The same conclusion has \f r 2 3 4 Fig. II.— (Henderson and Barringer.) Upstroke = diastole. Curves representing the change in the volume of the heart during a cardiac cycle, i, when the pulse is infrequent, 2 and 3, when the pulse is more frequent ; 4 shows rate of diastolic filling with small venous inflow. been reached by Henriques (1913) as the outcome of his more recent work. Hen- derson and Prince appear to have accepted this view, since they have recently (19x4) used the oxygen-consumption of the body as a basis for calculating the out- put of the heart. They define the oxygen-pulse as the amount of oxygen taken into, and consumed by, the tissues from the blood expelled during one heart-beat. Thus, if the oxygen-consumption is 2100 c.c, and the pulse-rate is 140 per minute, the oxygen-pulse is 15 c.c. Assuming the blood to lose half its oxygen during its passage through the tissues, and its oxygen-capacity to be 18 c.c. per 100 c.c. of blood, the output of the heart per beat would be 166 c.c. Henderson and Prince allow a smaller loss of oxygen from the blood, and conclude that, with a pulse-rate of 140 per minute, a powerful heart may put out 100 c.c. per beat and, therefore, 14 litres of blood per minute. During rest, with a pulse-rate of 60, the same heart might put out 150 to 160 c.c. per beat. Henderson and Prince regard these high figures as possible only when the heart is very powerful, and consider that the aver- age output per beat and per minute is distinctly less. According to Henderson and Prince, therefore, the output of the heart during rest is much greater, and during exercise much less, than that which Krogh and Lindhard and others have described as occurring in man. If this were the case, the supply of blood to the tissues would be excessive for the resting individual 62 THE PHYSIOLOGY OF MUSCULAR EXERCISE and inadequate during exercise. If, for example, the output of the heart per minute were 14 litres, the maximum which Henderson and Prince believe possible, and the oxygen-capacity were 18-5 c.c. per 100 c.c. of blood, the total amount of oxygen available for the tissues would be just under 2600 c.c. per minute, assuming the blood to be completely reduced during its passage through the capillaries. Yet a highly trained man may consume as much as 2500 to 3000 c.c. of oxygen per minute, although it is impossible to believe that complete reduction of the blood ever occurs during exercise. This constitutes a fatal objection to the acceptance of Henderson's view that the venous inflow to the heart is constant, and that, in the normal individual, the output per beat decreases as the pulse-rate accelerates during exercise. The large output per minute, which may occur during exercise, is indeed only possible if the venous inflow is at the same time greatly increased. Summary. In order to meet the demands of the tigsues for oxygen during exercise, not only a more rapid circulation rate but also a close correlation between the pulmonary ventilation and the circulation rate are required ; and such a correlation is present during exercise. The circulation rate round the body depends primarily upon the output of the heart, and this, which varies during rest from 3 to 5 litres a minute, may reach 20 litres or even more during heavy work. The larger output of the heart per minute involves a cor- responding increase in the diastolic filling of the heart. It is concluded that the heart does not possess any diastolic tone and that its filling is determined entirely by the venous inflow. During exercise the return of blood to the heart is increased partly by the active muscles, which mechanically squeeze blood out of their capillaries and veins into the great veins, and partly by the respiratory movements, particularly those of the diaphragm. In response to a larger venous inflow, the heart can increase its output per minute either by a larger output per beat or by acceleration of the pulse-rate. The output of the heart per beat is shown to depend upon " the law of the heart," which states that the force with which the heart-muscle contracts during systole varies directly with the volume of the heart at the end of diastole. The application of this law to the behaviour of the heart during exercise is discussed, as also is the influence of the nutritive condition of the cardiac muscle, and of the size of the cardiac musculature, upon its diastolic volume and output per beat. The conclusion is reached that dilatation of the heart normally occurs during exercise and is a strictly physiological process, since SUMMARY 63 dilatation of the heart, by increasing its contractile power in accordance with the law of the heart, enables the he^rt to in- crease its output per beat in response to a larger 'venous inflow. Such dilatation reaches its physiological limit when the heart at the end of diastole fills the pericardial sac. CHAPTER V. THE OUTPUT OF THE HEART {continued)— THE INFLUENCE OF THE PULSE-RATE UPON THE OUTPUT OF THE HEART— THE BE- HAVIOUR OF THE HEART DURING EXERCISE— THE MECHANI- CAL EFFICIENCY OF THE HEART. The Influence of the Pulse-Rate upon the Output of the Heart. The diastolic filling of the heart, and therefore its output per beat, depends not only upon the rate at which blood flows along the great veins into the heart but also upon the duration of diastole. Since the ventricular muscle is completely relaxed during systole, the rate at which the heart fills varies directly with the pressure under which blood flows from the great veins into the heart. If the changes in the volume of the heart at each beat under experimental conditions are graphically recorded (Patterson, Piper, and Starling), the form of the curves (Fig. 12) shows that, when the venous inflow is small, blood enters the heart at a fairly uniform rate throughout the diastolic period ; consequently the length of this period determines the volume of the heart at the end of diastole and, thterefore, its output per beat. If the duration of diastole is constant and the venous inflow small, the heart will not fill completely during diastole. If the venous inflow increases, the heart fills more rapidly, though still at a uniform rate ; and, since the fully relaxed heart-wall yields before the inflowing blood, the heart may fill to the limits im- posed by the pericardium just at the end of diastole. But, as the venous inflow to the heart becomes still larger, a point is reached at which blood flows into the heart so rapidly that this fills to, or almost to, its maximal size before the end of diastole, and the curve of the changes in the volume of the heart alters in shape (Fig. 12). Any further increase in the rate of venous inflow then merely causes the heart to become full still earlier during the diastolic period. This condition is termed by Krogh " adequate " filling of the heart. 64 INFLUENCE OF PULSE-RATE UPON THE HEART 65 Since the maximum extent to which the heart can fill during diastole is fixed by the pericardium, it is clear that, if the pulse-rate remains unchanged, an increase beyond a certain point in the rate at which blood returns to the heart must lead to the accumulation of blood in the great veins. Krogh (191 2) was the first to call attention to the significance of accelera- tion of the pulse in these circumstances. He pointed out that, if the venous inflow is so small that the heart slowly fills at a Fig. 12. — (Patterson, Piper, and Starling.) Downstroke = systole. Curve showing the change in ven- tricular volume during the car- diac cycle with varying venous inflow, this being smallest in curve I and largest in curve G. fairly uniform rate during diastole, an increase in the rate of the heart, though lessening its output per beat, will hardly affect its minute-volume. On the other hand, if the heart fills early in diastole, greater frequency of the pulse will very slightly diminish its output per beat, and its output p^r minute will increase almost in proportion to the rise in the pulse-rate. The correctness of this view has been demonstrated experimentally by Kuno (191 S), who showed that, provided the venous inflow was adequate, the output of the heart could be doubled by increasing the frequency of the pulse. 5 66 THE PHYSIOLOGY OF MUSCULAR EXERCISE TABLE XIII.— (KuNO.) Height of Venous Reservoir in cm. Venous Pressure in V. Cava (mm. in H2O). Pulse-Rate per Minute. Output of Heart per Minute. Output of Heart per Beat. 13 13 18 19-5 73 47 III 85 90 135 78 125 700 C.C. 955 .. 680 „ 1300 ,, 7-8 C.C. 7*1 .. 8-7 „ 10-3 „ The Venous Pressure. So long as the blood enters the heart from the great veins as rapidly as it reaches these veins from the peripheral veins, the pressure in the great veins remains low, since a very slight pressure suffices to distend the relaxed ventricular walls. But, as soon as the amount of blood flowing into the great veins ex- ceeds that which can enter, and be accommodated in, the heart during diastole, blood begins to accumulate in the great veins and the venous pressure rises. As a result of the higher pressure, the heart fills earlier in diastole and the diastolic pressure in the heart also rises. The higher pressure cannot appreci- ably increase the diastolic volume of the heart, since this is fixed by the pericardium ; and, so long as the rate of the heart remains unchanged, a rise of venous pressure beyond a certain level has little or no influence upon the output of the heart. Hence a high venous pressure implies that blood is being returned to the great veins and heart faster than the heart can transfer it to the arterial side of the circulation. The gradual rise of pressure in the great veins and heart, as the venous inflow increases, has been observed experimentally by Evans and Matsuoko (Fig. 1 3), by Kuno, and by Patterson and Starling ; jn the experi- ments of Patterson and Starling the pericardium was open. When these conditions are present, acceleration of the pulse at once lowers the venous pressure (Table XIII.), since, by in- creasing the output of the heart per minute, it lessens the accumu- lation of blood in the great veins. The Relation Between the Pulse-rate and the Contractile Power of the Heart. The part taken by the pulse-rate in extending the range of the output of the heart depends, not only on the venous inflow, INFLUENCE OF PULSE-RATE UPON THE HEART 67 but also on the contractile power of the heart Other things being equal, the absolute contractile power of the heart is pro- portional to the number and size of its fibres. Consequently, in response to a moderate increase in venous inflow, a comparatively slight dilatation enables a powerful (thick-walled) ventricle to increase considerably its output per beat and still to empty itself Fig. 13. — (Evans and Matsuoko.) Vv = volume of the heart; V.P. = venous pressure in mm. of water. O2 = oxygen-consumption of heart in c.c. per hour. Work = kg.m. per hour. At p the pericardium was opened. The work of the heart was increased by increasing the venous inflow to the heart. almost completely at each beat. Hence a slight increase in the pulse-rate will bring about a sufficiently large output per minute to prevent any accumulation of blood on the venous side and, therefore, to prevent an appreciable rise of venous pressure. Placed under the same conditions, a feeble (thin-walled) ventricle, even when dilated to its physiological limit, may be unable 68 THE PHYSIOLOGY OF MUSCULAR EXERCISE greatly to increase its output per beat and may be far from empty at the end of systole. In these circumstances, consider- able acceleration of the pulse will be necessary to increase the minute-volume of the heart sufficiently to balance the venous inflow. In this way acceleration of the pulse can compensate for lessened contractile power in maintaining the output of the heart per minute; and the less muscular the heart, the greater will be the pulse-rate required to maintain any given output per minute. Again, if the venous inflow and pulse-rate are constant, the feebler the heart and the less its output per beat, the greater will be the venous pressure and the diastolic volume of the heart, and the more rapidly will it fill during diastole. Acceleration of the pulse increases the output of such a heart per minute, thereby lowering the venous pressure and lessening the rate of filling and the diastolic volume of the heart ; and, if the pulse is sufficiently frequent, a comparatively feeble heart may maintain a consider- able output per minute without much increase in its diastolic volume. It may be concluded then, first, that the maximal output of the heart will be reached when the venous inflow and pressure are sufficient to fill the heart very rapidly and completely during diastole, and the frequency of the pulse is such that the next systole begins immediately the heart is full, and, secondly, that greater frequency of the pulse can compensate for lessened con- tractile power of the heart in maintaining or increasing its output per minute. The minute-volume of the heart is the product of its output per beat and of the pulse-rate ; its output per beat is the resultant of the rate of venous inflow, of the contractile power of the heart, and of the duration of diastole. It is clear that an intimate relationship must exist between the pulse-rate, the venous inflow, and the contractile power of the heart, if the optimal efficiency of the heart, as regards its minute-volume, is to be maintained. This relationship underlies, and furnishes the key to the inter- pretation of, the varying behaviour of the heart in different individuals during exercise. The question therefore arises, What is the link which correlates these three processes ? The question is a difficult one because the venous inflow depends mainly upon the mechanical pumping action of the muscles, the contractile THE REGULATION OF THE PULSE-RATE 69 power of the heart varies with its size and nutritive condition, and the pulse-rate is controlled by the central nervous system ; and, before an answer is attempted, the factors which regulate the pulse-rate must be considered. The Regulation of the Pulse-rate. Miss Buchanan (1909) was the first to show that, in man, the pulse quickens at the very outset of exercise, so that the first diastolic period, after exercise begins, is shorter than during rest. During the next few seconds, the acceleration of the pulse be- comes progressively greater (Table XIV.), and, within one to two minutes, it reaches a fairly steady level, which is then maintained so long as the work continues. The rate finally reached depends upon the severity of the exercise, and upon the degree to which the subject is in training. TABLE XIV.— (Miss Buchanan.) ("After Hearing Subject. . Resting. iSec. 2 Sees. 10 Sees. 20 Sees. 1-2 Mins. 5-7 Mins. < Signal to L Begin Work. R. W. D. 42 74 84 90 105 120 120-127 W. B. 55 67 80 96 100 100 "5 W. Ch. 58 7« 85-90 100 100 140 150 C. G. D. 60 72 75 84 88 96-108 100 G. H. B. 64 72 80 go 90 100 100-103 R. P. H. 68 100 106 120 124 135-140 135-140 F. B. S. H. 72 90 96 105 108 IIO 120 The initial acceleration of the pulse is brought about solely by shortening of the diastolic period ; and this, as Hunt ob- served (1899), is characteristic of loss of vagus tone as distinct from stimulation of the accelerator nerves, which leads to shorten- ing of systole as well as diastole. This fact, and the promptness with which the acceleration begins at the outset of exercise, leave no doubt that the effect is due entirely to loss of vagus tone. Johansson (1893) found that in rabbits the initial quicken- ing of the pulse was absent when the limbs were passively moved ; and this observation has been confirmed for man by Krogh and Lindhard (i9i3)j who accept Johansson's conclusion that the initial acceleration of the pulse in voluntary movement is the result of an outflow of impulses from the cortical motor centres to the vagus centre. 70 THE PHYSIOLOGY OF MUSCULAR EXERCISE There is reason to believe, however, that increase of accelerator tone also contributes to the quickening of the pulse early in exer- cise, although, owing to the long latent period, this may not come into action for a few seconds after the beginning of exercise. Gasser and Meek (19 1 4) found that, after section of the vagi and excision of the suprarenal glands, acceleration of the pulse oc- curred when the animal took exercise, and they regarded this as due to greater accelerator tone. Again, the reflex acceleration of the pulse brought about by stimulation of a sensory nerve is due, not merely to loss of vagal tone, but also to a concomitant increase of accelerator tone (Bainbridge, 191 4). Since such stimuli normally evoke reflex movements, it is probable that the vascular changes induced by sensory stimuli are identical in character with those usually observed during exercise. Further, some observations of G. Bourne^ indicate that loss of vagal tone alone would not account for the pulse-rate often observed during even the early stages of exercise. He found that, after the ad- ministration of a dose of atropin sufficient to eliminate the in- fluence of the vagus on the heart, the pulse-rate in a number of healthy men at rest did not exceed 100 to no. The acceleration of the pulse during exercise must, therefore, be looked upon as the outcome, partly of lessened vagal tone, and partly of greater accelerator tone. The Continued Increase in Pulse-rate. Although the initial increase in the pulse-rate is purely psy- chical in origin, the persistence of increased frequency of the pulse throughout the period of exercise is of very complex causation. It is almost certainly due in part to a continued outflow of impulses from the higher centres to the vagus and accelerator centres. There is no doubt, however, that, even when the psychical factor is excluded or reduced tp a minimum, induced muscular movement increases the frequency of the pulse. Mansfeld (1 910) showed that, in animals, after division of the spinal cord in order to exclude centripetal nervous impulses, tetanisation of the hind limbs led, after a few seconds, to a con- siderable acceleration of the pulse ; the effect was obtained only if the vagi were intact. Mansfeld suggests that the acceleration is due to stimulation of afferent nerve-endings in the heart by ^ Private communication. THE REGULATION OF THE PULSE-RATE 71 a rise in the temperature of the blood. The evidence in support of this suggestion is, however, not very convincing, and there are other possible explanations of Mansfeld's results. Apart from psychical influences, the possible causes of accelera- tion of the pulse during exercise are (i) the passage of adrenalin into the blood in larger amount ; (2) rise of the temperature of the body ; (3) irradiation of impulses from the respiratory to the vagus centre ; (4) some effect of the increased H' ion concentration of the blood upon the tone of the vagus centre, and (5) a rise of venous pressure. The scanty evidence available does not suggest that a larger discharge of adrenalin into the blood contributes to the increased frequency of the pulse when exercise is carried out under the ordinary conditions of daily life. Gasser and Meek found that, when the heart was freed from all nervous control, exercise led to a slight increase in pulse-rate which could be accounted for by a rise of temperature. Marked ac- celeration of the pulse only took place if, owing to the condition of the animals, their oxygen-supply was inadequate. They con- clude, therefore, that, during normal exercise, the discharge of adrenalin into the blood-stream is insufificient to affect the pulse- rate. The possibility that, when exercise is carried out under emotional stress, adrenalin may enter into the blood-stream in sufficient amount to quicken the heart will be considered later. The temperature during exercise does not usually exceed lOi" to 102° F. (38"3° to 38-9° C), although a temperature of 104° F. (40° C.) or 105° F. (40-5° C.) has been recorded by L. Hill (1910) and by Savage and Barasch; and there is ample evidence, the most recent being that furnished by Markwalder and Starling (191 3) and by Matsuoko and Evans (191 5), that such a rise in the temperature of the circulating blood produces only a trivial acceleratiori of the isolated heart. But in the normal individual, as L. Hill and also Haldane and Boycott (1905) have shown, a rise of body-rtemperature (apart from exercise) may be accompanied by a marked increase in pul- monary ventilation and pulse-rate. Since the alveolar tension of carbonic acid falls and the H ■ ion concentration of the blood is presumably not increased, the increased pulmonary ventilation must be the result of greater excitability of the respiratory centre ; and it has been assumed (Pembrey) that the acceleration of the 72 THE PHYSIOLOGY OF MUSCULAR EXERCISE pulse is also due to some effect of the temperature upon the tone of the vagus centre. It is not altogether easy to understand how a greater excitability of the vagus centre can lessen its tonic action except on the assumption that this tone is of reflex origin, and that the impulses which tend to increase, and those which tend to lessen, vagal tone normally balance, this balance inclining towards loss of vagal tone when the centre itself becomes more sensitive to afferent impulses. That the vagus tone is maintained reflexly under normal conditions is very probable, although it is difficult to prove that such is the case ; but the cause of the diminution of vagal tone, which is associated with a rise of the temperature of the body, has not been fully investigated. It might be suggested, however, that the acceleration of the pulse in these circumstances is really secondary to the greater activity of the respiratory centre which is also brought about by a rise of body-temperature. That a close correspondence often exists between the extent of the respiratory movements and the frequency of the pulse has already been pointed out ; it holds good not only during exercise but under other conditions, sucn as at high altitudes and during apncea. Since both the pul- monary ventilation and the pulse-rate usually vary directly with the oxygen-consumption of the body (Fig. 8), the increased pulse-rate during exercise might seem to be fully explained by supposing either that an irradiation of impulses takes place from the respiratory to the vagus centre, or that the vagus centre, like the respiratory centre, is affected by raised H • ion concentration of the blood. But the belief that such an irradiation or overflow of impulses can, or does, occur rests on very slender evidence, and, at least under experimental conditions, the relationship between the pul- monary ventilation and the pulse-rate is by no means so close as is often supposed. Even during exercise in man. Means and Newburgh (191 5) find that the pulmonary ventilation and pulse- rate do not invariably run parallel. Moreover, Bainbridge and Hilton (1919) have brought forward evidence that, when the in- fluence of the respiratory movements upon the circulation is excluded by opening the chest and cutting the phrenic nerves, increased activity of the respiratory centre does not alter the frequency of the pulse. Under the same conditions, the tone of the vagus centre is not lessened by a slight rise in the H • ion THE REGULATION OF THE PULSE-RATE 73 concentration of the blood, although, as Hill and Flack (1908) showed, a marked rise in the H- ion concentration of the blood slows the heart. If these observations hold good, they point to the conclusion that neither irradiation from the respiratory to the vagus centre, nor the altered reaction of the blood, will account for the continued acceleration of the pulse during exercise, and that some other factor xnust be' responsible for the acceleration. This factor ap- pears to be the venous pressure. , Bainbridge ( 1 9 1 5 ) has shown that a rise of yenous pressure brings about acceleration of the heart, which is due partly to loss of vagal tone and partly to increase of accelerator tone. The acceleration is reflex in origin, the afferent path being along the vagus nerves. The effective stimulus is either an adequate rise in venous pressure or, more probably, a sufficient increase in the diastolic volume of the heart to set up a slight diastolic tension in its muscular fibres. There is no evidence to show whether the stimulus originates only on the right side of the heart, or whether it can arise on both sides. That the venous pressure rises during exercise was first ob- served by Hooker (191 1). He found that the pressure in the veins of the hand, which varied from 28 to 80 mm. of water during rest, rose 100 mm. or more during exercise which, in his ex- periments, consisted in pedalling a bicycle ergometer. The rise in pressure took place very shortly after the exercise began and continued throughout its duration. Similar results have been obtained by Schneider, who also noted that the pressure did not return to normal for some time (eight to twelve minutes) after the conclusion of the exercise. Since a greater venous inflow at the same time causes the heart to fill more rapidly and completely during diastole, and, by means of this reflex mechanism, leads to acceleration of the pulse, it is clear, not only that the larger venous inflow during exercise must bring about acceleration of the pulse, but also that it furnishes a link whereby the diastolic filling of the heart and the pulse-rate can be correlated in such a way as normally to ensure the optimal efficiency of the heart. It should, however, be noted that deeper breathing, especially if this is mainly diaphragmatic, by bringing about a more rapid return of blood to the heart, will increase the diastolic filling 74 THE PHYSIOLOGY OF MUSCULAR EXERCISE and volume of the heart ; and it is quite probable that, in this indirect fashion, more vigorous respiration may contribute very considerably to acceleration of the pulse during exercise. It may be concluded, therefore, that the greater frequency of pulse throughout the per ioJot exercise is due to the interaction of three factors. The first is a continued outflow of impulses from the higher centres to the vagus centre, the second is reflex decrease of vagal tone and increase of accelerator tone induced by distension of the heart, and the third is a rise in the tempera- ture of the body. The Behaviour of the Heart During Exercise. / It has been shown, in the foregoing discussion, that the ; minute-volume, and the diastolic and systolic volumes, of the heart are determined by the venous inflow, the pulse-rate, and Jjthe contractile power of the cardiac muscle ; and these facts may now be applied in the interpretation of the behaviour of the i^eart during exercise. At the outset of exercise the heart dilates, partly in order to maintain its output in the face of the rising arterial pressure and, possibly, partly because, until the higher pressure drives more blood through the coronary vessels, the blood-supply to the heart is not quite adequate and its contractile power (for a given diastolic volume) decreases slightly. But the concomitant initial acceleration of the pulse keeps the dilatation within moderate limits, and the rapidly increasing coronary blood-flow quickly restores or even improves the tone of the cardiac muscle and tends to lessen the volume of the heart. "For a few moments the acceleration of the pulse, brought about by the higher centres, has little or no effect upon the output of the heart per minute, since the venous inflow to the heart does not increase for some seconds after the beginning of exercise. As soon as this occurs, the diastolic volume of the heart becomes larger, its output per beat increases, and the pulse-rate becomes still more rapid ; and the output per minute soon varies almost directly with the oxygen-consumption of the body, that is to say, with the intensity of the exercise. Two factors appear to be at work in bringing about the co-ordination between the output per beat and the pulse-rate which is necessary to maintain this relationship between the THE BEHAVIOUR OF THE HEART DURING EXERCISE 75 minute-volume of the heart and the amount of muscular work performed. In the first place, the greater outflow of impulses from the higher centres to the vagus centre, as the exercise becomes more vigorous, accelerates the pulse concomitantly with the larger venous inflow to the heart produced by the more active muscular movements. Tn^jj ie sprnnH p1qr g,_1JTp_jrnnre active the^y.{'rri'se,jthe^ greater will be the return of blood to t he heart ; and this, partl y by increasing t hediastolic volume of the heartr~ and partly by evoking reflex acceleration of the pulse, leads to a corresponding increase in the output of the heart per minute. The slightest failure in the normal correspondence be- tween the output of the heart per minute and the amount of work performed by the active muscles at once leads to the accumula- tion of blood in the great veins, and hence to greater distension of the heart. This causes further acceleration of the pulse, thereby increasing the output of the heart and restoring the balance be- tween the output of the heart and the severity of the muscular ,work. The accuracy of these adjustments is shown by the fact that the output of the heart is practically a linear function (Fig. 8) of the oxygen-consumption of the body during exercise. Evidence of the co-ordinating action of these processes is also furnished by the observation that, when the amount of muscular work done and the output of the heart per minute are the same in each case, the pulse-rate is less in the trained than in the un- trained man. In the former, the output of the heart per beat is such that a comparatively slight increase in pulse-rate is required to maintain the necessary relationship between the output of the heart per minute and the degree of muscular work, and to prevent undue rise of venous pressure or inadequate oxygen-supply to the muscles. In the untrained man, whose heart has less contractile power, the output per beat must be supplemented to a much larger extent by acceleration of the pulse in order that the out- put per minute may correspond with the severity of the muscular work, since his heart empties itself much less completely during systole than that of the trained maa Indeed, broadly speaking, the acceleration of the pulse for a given intensity of muscular exertion varies inversely with the contractile power of the heart. The effectiveness of this mechanism will be modified by the extent to which the vagus (and accelerator) centres are directly or indirectly played upon by emotional impulses from the higher 76 THE PHYSIOLOGY OF MUSCULAR EXERCISE centres or by a rise in the temperature of the body ; and, owing to these processes, the pulse-rate during exercise is sometimes so rapid that it not merely supplements, but may actually replace, an increased output per beat in maintaining the minute- volume of the heart. In these circumstances, the diastolic volume of the heart for a given output per minute will naturally be less than would otherwise be the case. During heavy muscular work, however, the venous inflow to the heart must be so large that every heart dilates almost to its full size during diastole, and its output per beat reaches its limit ; the output of the heart per minute then becomes directly propor- tional to the pulse-rate. The maximal pulse-rate attained during exercise, whether the individual is trained or not, appears rarely to exceed i6o per minute, although Benedict and Cathcart have recorded a pulse-rate of 1 80 in a highly trained subject perform- ing very heavy work. Since the maximum pulse-rate is com- paratively constant, the maximal output of the heart per minute in different individuals must ultimately depend upon the capacity of the heart to increase its output per beat, or, in other words, upon its contractile power. If the nutrition of the cardiac muscle is normal, the contractile power of the heart is proportional to its muscular development, and the more muscular the heart, the more completely will it empty itself at each beat. Hence the powerful heart of a trained man is capable of reaching an output per minute far exceeding that which can be attained by the heart of a sedentary person ; and since, as will be seen later, the intensity of mus- cular exertion of which a man is capable is very largely deter- mined by the maximal output of his heart per minute, no man can be an athlete who does not possess a powerful (i.e. muscular) heart. In the case of two subjects, one trained and one un- trained, working near the limits of their power, and whose out- put was almost maximal, Lindhard obtaihed the following figures : — TABLE XV. Work Done, Kgm. per Min. Output of Heart, Litres per Min. Pulse-Rate per Min. Oxygen Consumed per Min. (1) Trained subject {j°^^ . (2) Untrained subject 386 /22-6 \28-6 107 148 150 2583 1070 C.C. THE MECHANICAL EFFICIENCY OF THE HEART 77 The Mechanical Efficiency of the Heart. The ability of the heart to maintain or increase its output is determined partly by the total energy set free at each beat and by the pulse-rate, and partly by the fraction of this energy which appears as effective work ; and the relation between the work done by the heart and its total expenditure of energy represents its gross mechanical efficiency. Since, during violent exercise, the heart may send out per minute four or five times as much blood as during rest, and this against a much higher arterial pressure, its external work is very greatly increased. It becomes of interest, therefore, to inquire whether the total expenditure of energy by the heart is correspond- ingly increased, what is the effect of exercise upon its efficiency as a machine, and whether training or other conditions have any influence upon the efficiency of the heart. Light has been thrown on these questions by Evans. Taking the oxygen-consumption of the isolated heart as a measure of its total expenditure of energy, and at the same time recording the mechanical work performed by the heart, Evans (19 12), and Evans and Matsuoko (1915), have investigated the conditions which influence its total expenditure of energy and its efficiency. The energy-expenditure of the heart was calculated in terms of work from the equation i c.c. oxygen consumed = 2'o7 kilogrammetres of work. The work 7OR ze/V^ done by the heart was calculated from the formula Work -= '-| — + , where Q = fi g volume of blood expelled in litres, R = arterial resistance in metres of blood, w = weight of blood expelled in kilogrammes, V = mean velocity of the blood at the root of the aorta, and g = acceleration due to gravity. Evans and Matsuoko took V to represent the mean velocity of the blood-flow, but Starling has pointed out that the velocity with which the blood leaves the heart during systole is a more accurate basis for determining the share taken by the velocity- factor in the work of the heart. The velocity of the blood-flow during the period when blood is entering the aorta can be approximately calculated by multiplying the mean velocity of the blood-flow by the factor duration of cardiac cycle duration of period of ventricular expulsion. Evans has recently (igi8) applied this correction to his earlier results, and he finds that the fraction of the heart's energy used in imparting velocity to the blood is much larger than was previously supposed, and that, consequently, the mechanical efficiency of the heart is greater than his earlier observations led him to believe to be the case. The main conclusion which they reach is that, in cardiac as in skeletal muscle, the total expenditure of energy during 78 THE PHYSIOLOGY OF MUSCULAR EXERCISE contraction varies directly with the initial length of the fibres, and that, if the pulse-rate is constant, the oxygen-consumption of the heart is proportional to its diastolic volume (Fig. 13). Since the mechanical energy set free during systole is also pro- portional to the diastolic volume of the heart (Patterson, Piper, and Starling), the mechanical efficiency of the heart might be expected to remain constant, whether it is doing much or little work. But Evans and Matsuoko find that, when more work is thrown upon the heart either by a rise of arterial pressure or by a larger venous inflow, its dSiCVtacy progressively increases up to a maxi- mum, which appears to be reached when the diastolic volume of the heart approaches its physiological limit. They attribute the greater efficiency, as the arterial pressure rises to the fact that, as Patterson, Piper, and Starling showed, the expulsion period of systole is prolonged and a longer time is available for the con- version of the heart's energy into mechanical work ; and they consider that, when the venous inflow is increased (Fig. 14), the heart is more efficient, probably because the endocardiac pressure is greater and the velocity with which blood leaves the heart is correspondingly larger. In some of their experiments the opti- mal gross efficiency of the heart reached 28 per cent., a figure higher than is reached by the body as a whole even when work- ing under favourable conditions. TABLE XVI. — Efficiency of the Isolated Heart (Evans and Matsuoko). Arterial Pressure. Output per Hour. O2 Consumed per Hour. Kg. Metres Work per Hour. Mechanical Efficiency. 80 80 80 Litres. lyo 33-8 8i C.C. 140 150 299 21-2 467 175-0 Per Cent. 7-3 28-2 There are reasons for believing, however, that the varying efficiency of the heart observed by Evans and Matsuoko is largely the outcome of the conditions of their experiments, and that the efficiency of the normal heart is practically constant during rest and work. The energy-expenditure of the heart per minute is the product of the production of energy per beat and of the pulse-rate ; and every rise in the pulse-rate, therefore, in- creases the total expenditure of energy of the heart. If the venous THE MECHANICAL EFFICIENCY OF THE HEART 79 inflow is small, greater frequency of the pulse lessens the dia- stolic volume of the heart and hence the production of energy per beat is less ; but Evans' experiments on the influence of rate upon the consumption of oxygen by the heart indicate that the 92. doo / / f /...- ... - .0 ,*'*"' ■ 7 /-" / 'WO / / / / t / t / t / t / •*-« ilK> c J » 1 V A « i.-f-y V 9^ T ^K,.r .WotV ' V i 5 o 1 5 1 OO 1 A I so r tS 2 90 u I |5 15 Fig. 14. — (Evans.) Dotted line = percentage efficiency. . Continuous line = oxygen-consumption of heart in c.c. per hour. The figures on the continuous line indicate the output of the heart in litres per hour, kilogram- metre work = work per hour. smaller consumption per beat is more than counterbalanced by increase in pulse-rate, and that the consumption of oxygen per minute is increased. With a large venous inflow, increase in pulse-rate has much less effect upon the diastolic volume, and 8o THE PHYSIOLOGY OF MUSCULAR EXERCISE consumption of oxygen per beat and the energy-expenditure of the heart are almost a linear function of the pulse-rate. Since, when the venous inflow is small, the output, and there- fore the work, of the heart per minute are almost constant, what- ever the pulse-rate may be, acceleration of the pulse by increasing the total energy-expenditure of the heart, but not its work, lowers its mechanical efficiency. On the contrary, when the venous inflow is large, both the output of the heart and its expenditure of energy are proportional to the pulse-rate. Hence it is clear that, in order to obtain a constant and optimal efficiency of the heart, the pulse-rate must correspond fairly closely with the venous inflow. Acceleration of the pulse, if unaccompanied by a larger venous inflow and output of the heart (or by a higher arterial pressure), is uneconomical and involves a useless expendi- ture of energy. The varying efficiency of the heart, observed by Evans and Matsuoko appears, therefore, to be due to the fact that, in their experiments, the pulse-rate was constant and very rapid ; conse- quently, with a small venous inflow, the heart was liberating energy in excess of its needs and its efficiency was low, whereas, with a large venous inflow, the energy was more effectively trans- formed into work. Their experiments were carried out on the heart-lung preparation, in which, owing to the elimination of nervous control, the rhythm of the heart is constant and much more rapid than that of the normal heart. In the normal heart, however, the pulse-rate and the output of the heart usually run almost parallel, and the efficiency of the heart is practically constant both during rest and during exercise, so long as the diastolic volume of the heart does not exceed the normal limits. The maximum efficiency recorded by Evans and Matsuoko was observed when the venous inflow was large and the pulse-rate rapid. This is comparable with the state of things existing during exercise, and it probably represents most truly the efficiency of the heart beating under ordinary conditions in the body. The ability of the heart to maintain this high efficiency, even when its work is enormously increased, is an excellent example of its powers of adaptation to the demands placed upon it during exercise. It is also probable that the rise in efficiency, which Evans observed to follow a rise of arterial pressure, was also dependent THE MECHANICAL EEFICIENCY OF THE HEART U Upon the great frequency of the pulse, and that, under normal conditions, the efficiency of the heart is unaffected by the arterial pressure, provided that the pulse-rate varies with the pressure as is the case during exercise. Although the efficiency of the heart is constant in the same individual, it does not follow that in all individuals the mechanical efficiency is the same. It has been pointed out (p. 52) that, during moderate exercise, the trained individual increases the minute-volume of his heart by a larger output per beat rather than by an increase in the pulse-rate, and it might be anticipated that this would involve a smaller expenditure of energy, and that the heart of the trained man would be more efficient, in the technical sense, than that of the untrained man. The available data do not show decisively how far this deduction is justifiable, although there is some evidence (Table XVII.) that the consump- tion of oxygen by the heart is less, and its efficiency greater, when a given minute-volume is maintained by a larger output per beat than when it is effected mainly by increasing the pulse- rate. If this is the case, the greater the contractile power of the heart the higher will be its efficiency. In the experiments shown in Table XVII., however, the changes in the pulse-rate were produced by altering the temperature of the heart itself, and it has not yet been shown that the results hold good for the normal animal in which variations in the pulse-rate are effected through the vagi. TABLE XVII.— (Evans.) Pulse-Rate. Output of Heart per Hour in Litres. Oxygen-Consumption per Hour in c.c. Efficiency. Kgm. in Work per Hour. 162 64 ^ 243 24'3 165 117 10-8 % 15-2 7o 37 37 Thfe conclusion that the efficiency of the heart is constant and high holds good only for the normal heart in which the pericar- dial sac has not been stretched beyond its physiological limit. If, as a result of abnormal conditions, the pericardium has stretched, or if it has been opened under experimental conditions, the heart, as Starling has shown, can then dilate still further and can thereby greatly increase its expenditure of energy and its output. But 6 82 THE PHYSIOLOGY OF MUSCULAR EXERCISE such a heart has crossed the boundary which divides the normal from the pathological ; if called upon to do heavy work, it dilates more and more, and its energy is less and less completely trans- formed into mechanical work. The efficiency of the heart de- creases because, with the giving way of the pericardium, the cardiac muscle is contracting at a mechanical disadvantage which is accentuated by every further dilatation. The heart must, however, at all costs maintain its output if the circulation is to be carried on, although, in these circum- stances, the performance of a given amount of work, and particu- larly of heavy work, necessitates a large and wasteful expenditure of energy ; and, with increasing dilatation and steadily declining efficiency, a point will be reached at which it can no longer transform into work sufficient energy to increase its output or even to maintain a normal output. When this stage is reached, failure of the circulation is at hand. Summary. . The influence of acceleration of the pulse upon the output of the heart per minute is determined by the rate at which the heart fills during diastole. If the venous inflow is small, the heart fills at a fairly uniform rate during diastole, and increased frequency of the pulse, while lessening the output of the heart per beat, scarcely affects its output per minute. If the venous inflow is so rapid that the heart fills almost completely early in diastole, acceleration of the pulse only slightly diminishes the output of the heart per beat, and its output per minute increases almost pro- portionately with the acceleration of the pulse. In these cir- cumstances, the acceleration of the pulse, by enabling the heart to transfer blood more rapidly from the venous to the arterial side, also brings about a fall of pressure in the great veins. The output of the heart per minute is the product of its out- put per beat, which ultimately depends upon the contractile power of its fibres, and of its rate. Hence, the smaller the output per beat, the greater will be the frequency of the pulse necessary to maintain a given output per minute, and in this way greater frequency of the pulse can compensate for lessened contractile power of the heart-muscle. The initial acceleration of the pulse-rate at, or just before, the beginning of exercise is due to the passage of impulses from SUMMARY 83 the higher centres to the vagus centre whereby its tone is lessened ; an increase of tone of the accelerator nerves is also partly respon- sible for the quickening of the pulSe early in exercise. The persistent acceleration of the pulse throughout the period of exercise depends, partly" on a continuance of the outflow of impulses from the cerebral cortex to the vagus and accelerator centres, partly on the influence upon the vagus centre of the rise in the temperature of the body, and partly on the greater diastolic distension of the heart which reflexly lessens the tone of the vagus centre. In each individual there is, as a rule, a close correspondence between the intensity of the muscular work and the frequency of the pulse. Reasons are given for concluding that this relation- ship is the result of two processes. In the first place, the out- flow of impulses from the motor cerebral cortex to the skeletal muscles probably runs parallel with that to the vagus and ac- celerator centres. In the second place, the return of blood to the heart, and therefore the venous pressure, vary directly with the activity of the muscles. Since the maximal pulse-rate during exercise is much the same (about 160) in different individuals, the maximum output of the heart per minute, which varies in different subjects, de- pends upon its capacity to increase its output per beat, that is to say, upon the contractile power of its fibres. The gross mechanical efficiency of the heart (20 to 30 per cent.) is higher than that of the body as a whole, and in the normal man the heart is probably equally efficient both during rest and during exercise. The efficiency of the heart diminishes if ac- celeration of the pulse occurs without a corresponding increase in the output of the heart per minute- or if the heart becomes dilated beypnd its physiological limits. CHAPTER VI. THE BLOOD-SUPPLY TO THE ACTIVE ORGANS DURING EXERCISE —THE ARTERIAL PRESSURE. Although the output of the heart is the most important means by which the blood-supply to the active muscles, the heart, and the brain is increased during exercise, other changes also occur in the circulatory system at the same time and add greatly to its effectiveness in this respect. These are an altered distribution of the bloodj which is largely diverted from the abdominal organs into the active tissues, a rise of arterial pres- sure whereby the blood is driven more rapidly through the muscles, heart, and brain, and, in the case of the muscles and heart, local 'dilatation of their vessels. Very few data are a,vailable either as to the actual blood-flow through the muscles during exercise or as to the share taken by these factors and by the output of the heart respectively in increasing this flow. Numerous observations have been made, under experimental conditions, upon the blood-flow through single muscles or small groups of muscles when resting or when thrown into contraction for a short time, and an increased rate of flow during contraction was almost invariably found. But the conditions existing in these experiments are so different from those present during normal exercise that the results are not of great value. The only investigation of this kind carried out under approximately normal conditions is that of Chauveau and Kauff'man (1892), who observed a fivefold increase in the blood-flow through the leuator labii superioris in the horse during mastication. The work of Krogh and Lindhard (19 1 2), however, has yielded figures from which it is possible to make a rough calculation of the blood-flow through the muscles during heavy work. In one experiment the following figures were obtained by Lindhard : — 84 THE BLOOD-SUPPLY TO THE ACTIVE ORGANS TABLE XVIII. 85 Rest. Work. Output of heart per minute .... Output per beat Pulse-rate Oxygen-consumption per minute Coefficient of utilisation .... 5'0 litres 72 c.c. 70 310 c.c. o'36 20-8 litres I20'5 c.c. 166 1891 c.c. 0-46 The early work of Ranke (1871) and of Spehl (1883) led them to conclude that, during rest, approximately one-third of the total blood is present in the skeletal muscles. Accepting this figure, which seems quite a probable one, one may make the further assumption that during rest one-third of the heart's out- put flows through the muscles, namely, in this case, I '66 litres per minute. There is no doubt that most of the increased con- sumption of oxygen during exercise occurs in the active muscles (including the heart), and, in the present example, the additional oxygen which they consumed is taken to be 1,200 c.c. This involves the passage through the muscles of 1 2 "69 litres of blood in addition to that flowing through them during rest, giving a total of 1 4 '3 litres, which represents more than an eightfold increase of the blood-flow through the muscles. As a result of such calculations from similar data in other individuals it appears that, during exercise, the blood-flow through the muscles may be from four to nine times greater in the trained man, and from three to six times greater in the un- trained subject, than during rest. TABLE XIX. Oxygen Consumed: c.c. per Minute. Output of Heart : Litres per Minute. -Calculated Increase in Blood-flow through Muscles. (i) Trained man — - Rest Heavy work (2) Untrained subject — Rest Moderate work 248 2158 223 . 1070 4-3 17-85 4'i 107 g-2 fold 6 fold Calculations of this kind can only furnish a rough indication of the magnitude of the blood-flow through the muscles. But, if 86 THE PHYSIOLOGY OF MUSCULAR EXERCISE they are even approximately correct, they make clear the im- portance of the share taken by the altered distribution of the blood, the raised arterial pressure, and local vascular changes in increasing the blood-flow through the active muscles. The Arterial Pressure. Although the co-operation of all these factors is necessary iiefr the maintenance of a sufficient supply of blood to the muscles, the most important is undoubtedly the rise of arterial pressure ; and this appears to be particularly the case as regards the heart and the brain. So far as is known, the blood-supply to the brain is determined entirely by the mean arterial pressure ; and, in the case of the heart, Markwalder and Starling (191 3) have shown that the coronary blood-flow normally depends to a much greater extent upon the arterial pressure than upon any other factor, and that it may become inadequate for the nutrition of the heart, if the arterial pressure falls below 90 mm. Hg. The extent to which the arterial pressure influences the blood- supply to the tissues is indicated by the work of Gesell (1918), who has found that the blood-flow through a single organ is not directly proportional to the blood-pressure, and that a compara-^ tively small fall in arterial pressure brings about a relatively larg^ decrease of the blood-flow through such an organ. This is alsc brought out by the observations of Robertson and Bock (1918).^ They have found that the supply of oxygen to the tissues can \ be maintained in spite of a greatly diminished oxygen-carrying \ power of the blood, provided the arterial pressure is kept up;"] and a man is better off, under these conditions, than one whose blood-pressure is low, even although, in the latter, the oxygen- carrying power of the blood is normal. Since a normal arterial pressure is required to bring about a sufficiently rapid blood-flow round 'the body to meet its demand for oxygen during rest, it is clear that a rise of arterial pressure is absolutely necessary when this demand is increased by exer- cise, and that a high arterial pressure is an essential condition for the efficient performance of muscular work. Direct evidence that the arterial pressure rises during exer- cisejin man was obtained by Zadek (1881), but L. Hill (1898) was the first to measure the rise of pressure, his observa- tions being made just after the conclusion of the exercise. A THE ARTERIAL PRESSURE 87 little later (1904), Bowen followed out the course of the arterial>, pressure throughout the whole period of exercise. He observed a rapid rise of pressure at the very outset of exercise, succeeded by a more gi-adual further rise to a maximum, which was reached within five to ten minutes after the beginning of exercise. The pressure then remained fairly steady, though it showed a slight tendency to fall during the remainder of the period of work ; and an abrupt fall almost to the resting level of pressure took place as soon as the work ceased. The maximum rise of arterial pressure in different experiments varied from 60 to 70 mm. Hg, although the exercise, which consisted in pedalling a bicycle ergometer, was not heavy and did not amount to more than 400 kilogrammetres per minute. These results were confirmed by Lowsley (191 1), who adopted methods similar to those of Bowen. The conditions under which continuous records of arteri^'' pressure can be obtained during exercise are obviously limited;* and the impossibility of recording the blood-pressure during the progress oY most forms of exercise has led the majority of ob- servers to measure the arterial pressure immediately after the conclusion of muscular work. Pembrey and Todd (1908) found that, in an untrained person, the arterial pressure was raised, in different experiments, from 16 to 34 mm. Hg by running up and ^ down stairs for half a minute. In similar experiments carried out by Hill and Flack (1909) the rise of pressure amounted to 50 to 60 mm. Hg. The results obtained in this way have hitherto been regarded as representing the actual rise of pressure during the exercise. But Cotton, Lewis, and Rapport (191 7) have recently shown that, ten seconds after the end of a short period of vigorous exercise, the systolic pressure is little, if at all, above the normal resting level. It then rises rather steeply and reaches a maximum twenty to sixty seconds later ; the pressure then gradually falls, and finally returns to the normal resting level from one to four and a half minutes after the cessation of exercise (Fig. 15). They explain these facts as follows. Immediately, at the end of exercise the muscles relax, and the veins, which they believe to be depleted during exercise, fill up with blood, thereby momen- tarily robbing the heart of its supply and lowering the arterial pressure until the veins fill and overflow ; this overflow, by feeding the heart, again raises the arterial pressure, the rise representing THE PHYSIOLOGY OF MUSCULAR EXERCISE the continuance of the arterial pressure during exercise in so far as the latter is due to factors other than emptying of the veins into the arteries. The evidence already detailed (p. 48) goes to show, however, that the veins are full during exercise, and it seems more probable that the fall of pressure results from the sudden stoppage of the muscular pump when the exercise ceases ; this brings about a momentary stagnation of blood in the capil- laries, which is rapidly succeeded by restoration of the venous inflow to the heart as the capillaries gradually empty themselves into the great veins. Cotton, Rapport, and Lewis further found THE ARTERIAL PRESSURE 89 that, in ten healthy pien, the average rise of systolic pressure, half a minute after walking briskly up a single flight of thirty steps, was 31 mm. Hg; with rather more severe exertion, a rise of 40 rnmr^IIg wdiTo^served in some cases. In the light of this evidencejt ip - dear that a single record of the arterial pressure, taken just after exercise, does not necessarily represent the pressure "fe:k:rstltu r~?^S?^ ^ exercise, since there is no certainty that the maximum pressure just after exercise was re- corded. The results obtained tend to be too low, and the figures recorded by Bowen, Lowsley, and Cotton, Rapport, and Lewis leave no doubt that the rise in arterial pressure is very consider- able even during moderate exercise. The relationship between the rise of arterial pressure an d the degree ot muscular work has not bgeh fulIy'iriVKBtiga ted, an d it is not kn own whether , like the output of the hearty the arterial pressure varies directly with the severity of the exercise. Cotton, Lewis, and Rapport's obser- vations, however, indicate that the more v igorous the exercise the greater jthe rise of pressure, and the existenc"5~Tof-anltrect relationship between~the arterial pressure and the intensity of ' the muscular work performed appears probable. The Factors which Influence the Arterial Pressure During Exercise. The arterial pressure at any moment during exercise is the resultant of many factors, not all of which are under the control of the central nervous system. These are the output of the heart, vaso-constriction in the splanchnic area, and dilation of the vessels in the skin and muscles. The output of the heart has already been dealt with, and the part played by the other two factors may now be discussed. Constriction of the Splanchnic Vessels. The rapid and abrupt rise of pressure at the beginning of exercise is almost certainly psychic in origin, and is due to im- pulses passing to the vaso-motor centre, and thence to the splanchnic area, from the higher centres, and probably mainly from the motor area of the cerebral cortex. The fact that the initial rise of pressure is more pronounced when the exercise is 90 THE PHYSIOIOGY OF MUSCULAR EXERCISE carried out under emotional stress, and that, in these circum- stances, it may occur even before the exercise begins, points clearly to this conclusion. Some indirect evidence of constric- tion of the splanchnic vessels during exercise has been furnished by Weber (1907), who found that certain emotions, or the thought of taking exercise (not followed by actual movement), led to shrinking of the abdominal viscera and to expansion of the limbs. The rise of arterial pressure and the altered distribution of the blood in the body, consequent upon constriction of the splanchnic vessels, would adequately account for the expansion of the limbs in this experiment, and there is, in point of fact, no evidence that, at the beginning of exercise, the vaso-motor centre directly lessens the tone of the vessels of the limbs. To what extent, if at all, this initial effect persists throughout the period of exercise is uncertain, and direct evidence oti the point would be extremely difficult to obtain. But, on general grounds, it seems quite probable that a continuous stream of impulses passes to the vaso-motor centre as well as to the other medullary centres during the whole period of muscular work. Indeed it seems almost inevitable that this must occur if the raised arterial pressure and altered distribution of the blood, which are so necessary for the blood-supply to the active organs, are to be maintained. Further, the question arises as to whether the vaso- motor centre is also stimulated during exercise by increased H" ion concentration of the blood. Although it is well known that the vaso-motor centre can be excited in this way, it usually responds less quickly than the respiratory centre, under experi- mental conditions, when the H- ion concentration of the blood is increased either by adding carbonic acid to the inspired air or in the early stages of asphyxia (Mathison, 191 i)y This differ- ence may possibly be experimental in origin, since there is some evidence (Cathcart and Clarke) that the response of the vaso- motor centre to altered reaction of the blood is more easily dulled under the depressing influences of anaesthetics than that of the respiratory centre.. But the change in the reaction of the arterial blood during exercise is so slight that, in the absence of any direct evidence as to the C„ of the blood required to excite the vaso-motor centre under normal conditions, the ques- tion whether the reaction of the blood normally affects the centre during exercise must be left unanswered for the present. THE ARTERIAL PRESSURE 91 Local Changes in the Vessels. The rise of blood pressure and the altered distribution of the blood resulting from constriction of the splanchnic vessels, pre- suming this to continue throughout exercise, are in themselves sufficient to increase considerably the blood-flow through the muscles, heart, and brain. In the case of the muscles von Anrep (191 2) has shown that this is the case. But it is clear that the extent of this increase must be profoundly modified by the coincident occurrence of changes in the tone of the blood-vessels of the active muscles (including the heart). Such changes may be of nervous origin or may result from alterations in the com- position of the blood. Gaskell (1878) observed an increased blood-flow through the limbs on stimulating a motor nerve in a curarised animal ; and Bayliss (1901) has shown that the limbs receive both vaso-con- strictor and vaso-dilator nerves, although the extent to which these are distributed to muscles and skin respectively is not very clearly defined. Although the central nervous system clearly exercises some control over the tone of the arterioles in the muscles, it is not known how far, if at all, this controlling action is modified during exercise ; and the comparatively trivial influence apparently exerted by the nervous system over the arterioles in the muscles early led Gaskell (1880) to examine the effect of chemical products of muscular activity upon the arterioles. His observation that these dilate, when lactic acid is added to the perfusing fluid, formed the starting-point from which has de- veloped the current belief that the metabolic products of active organs lessen the tone of their arterioles, and thereby automatic- ally increase the blood-flow through these organs. The evidence recently brought forward by Dale and Richards (191 8) makes it clear that this view must be extended to include capillary, as well as arterial, tone. Variations in capillary tone had previously been described by Roy and Graham Brown (1879), and by Langley (1911), but Dale and Richards have examined the conditions necessary for its maintenance and the means by which it may be increased or decreased. From the present point of view the most important of their conclusions are, first, that the presence of an adequate supply of oxygen in the circulating blood is essential for the maintenance of tone both in 92 THE PHYSIOLOGY OF MUSCULAR EXERCISE the arterioles of the muscles and in capillaries, and, second, that capillary tone is lessened by the addition to the blood of small amounts of histamine. It is reasonable to assume that the loss of capillary tone, which takes place when the circulating blood is deficient in oxygen, is really dependent upon an increased H • ion concentra- tion resulting from this deficiency. Further, Dale and Richards suggest that the action of histamine is probably typical of that of other metabolic products, whose formation is constantly taking place in the tissues, and whose production is " accelerated by every excitatory or injurious influence which intensifies metabolic activity ". The fact that the capillaries, as well as the arterioles, are capable of variations of tone under the influence of metabolic products and of changes in H* ion concentration must be con- stantly borne in mind in considering the extent to which the blood-supply to the muscles can be increased during exercise by alterations in the composition of the blood. Some indicatioij of the degree of vaso-dilatation which may be produced by such metabolites, when muscular movement is carried out under more or less normal conditions and uncom- plicated by changes in arterial pressure or in the output of the heart, has been furnished by Verzar (191 2). He examined the eff'ect of a brief tetanus upon the blood-flow through a single muscle, cut off from the central nervous system but provided with its normal blood-supply, and found that, just after the tetanus, the maximal rate of blood-flow was five times greater than duringv rest. The magnitude of this change shows very clearly the im- portant part taken by metabolites as a whole in increasing the flow of blood through muscles ; and the local dilatation, induced in this way, must be especially valuable when muscular activity is limited to a few small muscles and the output of the heart re- mains almost unaltered. The Action of Acid Metabolites. The metabolites responsible for this change fall into two groups, namely, acid products of metabolism and metabolites other than acids. During normal muscular activity these are doubtless produced simultaneously, and it is not easy to assess the relative importance of these two factors. Gaskell's observa- tion (i 880) that the addition of lactic acid to the perfusing fluid THE ARTERIAL PRESSURE 93 dilates the arterioles in the muscles was confirmed by Bayliss (1901), who further found that the presence of an excess of car- bonic acid in the perfusing fluid had the same effect. In these experiments the perfusing fluid was Ringer's solution, and the addition of lactic or carbonic acid to such a fluid produces, a change in its H' ion concentration far greater than would occur if the same amount of acid were added to blood. Assuming that the effective cause of dilatation of the arterioles by acids is &■& -I 1 8a I a-i V 3o > ^. "J-? \ \ 1% in lb 15 -7-4 /■ \ e: ofc< 1 1 — ^ ?.n IMK .4V(^ f ~ ^ \ 1 O 1° .20 30 A 4-0 c 3 S'eo 10 10 20 30 40 50 60 70 80 90 100 Oxygen Tension: in m.m. Hg. Fig. 17. — Dissociation curve of Barcroft's blood (Barcroft). at sea-level. just after climbing 1,000 feet. pressure of 27-5 mm. Hg, the saturation of his blood was 13 per cent, less just after exercise than during rest. In these experiments the saturation of the blood was deter- mined after equilibrium between blood and oxygen had been at- tained. During exercise, however, the blood is flowing through the muscles several times as fast as during rest, and it is very unlikely that the dissociation of oxyhemoglobin reaches the equilibrium point. Consequently, the rate at which oxyhaemo- globin dissociates is the really important factor in this connection; and it is significant that, in Barcroft's experiment, the exercise ^. ■^. 4 / ^ y x^'' / // "? /, / f / » f /' / / 1 // / / /' J- / 104 THE PHYSIOLOGY OF MUSCULAR EXERCISE doubled the velocity of dissociation of oxyhaemoglobin relatively to the velocity of association. Mathison (191 1) was the first to show that the addition of small amounts of acid to blood greatly accelerates the rate at which its oxyhaemoglobin dissociates' under a low tension of oxygen. He suggested that this was caused by the increased H* ion concentration of the blood, produced by the addition of acid ; and the later work of Barcroft and his col- laborators has not merely confirmed Mathison's view, but has demonstrated the marked extent to which even a trivial increase in the H- ion concentration of the blood hastens the velocity with which oxyhaemoglobin can dissociate. The samples of blood, examined in Barcroft's experiment, were obtained from the general blood-stream ; and there are good reasons for believing that the H* ion concentration of the blood as a whole is distinctly less than that of the blood leaving the active muscles. It is probable, therefore, that, even during moderate exercise, as in Barcroft's experiment, the rate of dissociation of oxyhaemoglobin in the blood flowing through the active muscles may be much more than doubled, and that, during violent exercise, the local H- ion concentration of the blood in the active muscles may increase sufficiently to bring about very rapid dissociation of oxyhaemoglobin. Since the production of lactic and carbonic acids in the muscles normally runs parallel with the intensity of the muscu- lar exertion, a similar relationship probably exists between, on the one hand, the intensity of the exercise and, on the other hand, the local H' ion concentration of the blood in the capillaries of the muscles and, consequently, the rate at which oxyhaemoglobin dissociates in the capillaries of the muscles. The more rapid the dissociation of oxyhaemoglobin, the higher will be the tension of oxygen in the plasma, and the more quickly will oxygen diffuse into the tissues ; and, as the outcome of this series of inter-related processes, the active muscles (and heart) are enabled to take up oxygen in accordance Avith their varying requirements. Further, the rate at which oxyhaemoglobin dissociates is in- creased, not only by changes in the reaction of the blood, but also by a rise of temperature (Barcroft and Hill, Oinuma, 191 1). The influence of temperature is so considerable that a rise of 10° C. may double, or more than double, the rate of dissociation. The rise in the temperature of the body during exercise, must. THE PASSAGE OF OXYGEN INTO THE TISSUES 105 ' therefore, exert an appreciable influence upon the rate at which the blood parts with oxygen as it flows through the tissues. ^ Incidentally, it may be noted that the lessened affinity of haemoglobin for oxygen, which occurs during exercise, is much more effective in increasing the passage of oxygen from the blood to the tissues than in decreasing the extent to which the blood takes up oxygen as it flows through the lungs. There are two reasons for this difference. In the first place, the rate at which blood flows through the lungs depends entirely upon the output of the heart and, even during the heaviest work, is only four or five times greater than during rest, whereas the blood-flow through the muscles, in these circumstances, may be eight or ten times greater than during rest. Ih the second place, the tension of oxygen in the alveolar air is so high that a slight increase in the H ■ ion concentration of the blood scarcely affects the amount of oxygen taken up in the lungs ; on the contrary, in the tissues, where the oxygen tension is very low, a similar increase in the C„ of the blood enables the oxyhaemoglobin to dissociate much more readily. During vigorous exercise, the rate at which the blood flows through the active organs becomes so rapid that the time spent by any one fraction of the blood in the capillaries is con- siderably shortened. Consequently, although each red corpuscle gives up its store of oxygen more rapidly to the tissues, it has less time at its disposal for this purpose. The widening of the capillary bed allows the amount of blood flowing through the active muscles to be greatly increased with only a compara- tively small acceleration of the rate at which the blood traverses the capillaries. Moreover, the dilatation of the capillaries, by increasing the surface area of the blood flowing through them must facilitate the diffusion of oxygen into the tissue-fluid and muscle-fibres. But the coefficient of utilisation is often so large that some writers believe that the increased Ch of the blood is insufficient to account for the very marked reduction which the oxyhaemo- globin may undergo during exercise, and that other factors must be also at work. Lindhard, for instance, has suggested that possibly some catalase or reductase is produced during exer- cise, and that this lessens the affinity of haemoglobin for oxygen. There is, however, no evidence for the existence of such a catalase. io6 THE PHYSIOLOGY OF MUSCULAR EXERCISE' Again, some observations of Verz^r (1912) appear to indicate that a small but definite tension of oxygen is present in resting muscle, and, if this is the case, a fall in this tension during mus- cular activity would enable the muscle to take up oxygen more quickly from the blood. It is not easy, however, to understand how muscle can possess an oxygen-tension, since the evidence goes to show that no free oxygen is present in muscle or any other tissue (Fletcher and Brown), and Verzar's observations may perhaps be capable of some other interpretation: There is at present no ground for believing that oxygen enters the cells of the tissues except by diffusion from the blood by way of the tissue fluid ; and, if it is admitted that the tension of oxygen in the tissues, whether these are resting or active, is almost nil, the speed with which oxygen can diffuse into the tissues must depend entirely upon the rate at which oxyhaemoglobin dissociates as the blood flows through the tissue. But it is obvious that, unless the oxygen diffusing into the cell at once enters into some form of chemical combination, for example a peroxide, the ten- sion of oxygen in the cell will tend to rise. The rate at which the tissues seize upon the oxygen presented to them varies, of course, with their metabolic activity. It is conceivable, therefore, that a resting organ may not use at once all the oxygen reaching it, and that a small tension of oxygen may exist. But the avidity of the active tissues for oxygen is so large that the oxygen entering them is at once utilised, and the oxygen tension is kept at zero, even though the rate at which oxygen is diffusing into the tissues is much greater than during rest. It may be concluded, then, that the increased consumption of oxygen by the muscles (and heart) during exfercise depends upon two factors. In the first place, the active muscles utilise so rapidly, for oxidative processes, the oxygen reaching them by diffusion that the tension of oxygen within them is zero. In the second place, they increase the amount of oxygen reaching them from the blood by an indirect means, namely, a rise in the Ch of the capillary blood, this being normally brought about by the acid products of their metabolic activity and varying pari passu with their activity. There is no doubt that, as the outcome of these two processes, in conjunction with a larger blood-flow through the muscles, the consumption of oxygen by the muscles during exercise may be very large. But the direct measurement THE CONSUMPTION OF OXYGEN BY THE MUSCLES 107 of the oxygen-consumption of the muscles, under conditions ap- proximating to those present during exercise, presents such diffi- culties that comparatively few observations have been made. The Consumption of Oxygen by the Muscles. The problem was first attacked by Chauveau and Kaufmann (1887), who measured the blood-flow through the levator labii of the horse, and determined the oxygen-content of the blood entering and leaving the muscle. In these experiments no anaes- thetic was necessary, and the muscle was contracting under normal conditions and was not being artificially stimulated ; but the methods of blood gas analysis then available left much to be desired. They found that the oxygen-consumption of resting muscle varied from 0-0028. to 0-0079 c.c, and that of the active muscle from o-oi to 0-05 c.c, per gramme of muscle per minute. The same question has recently been investigated by Verzir (19 1 2), who determined the oxygen-consumption of the cat's gastrocnemius muscle, making use of Barcroft's technique. The muscle was thrown into activity by brief stimulation of the sciatic nerve. Verzar found the average oxygen-consumption of resting muscle to be 0-0044 c.c. per gramme per minute. A brief tetanus increased the consumption of oxygen during, and for some little time after, the tetanus ; and the total consumption of oxygen for the whole period, in one experiment, was at the rate of 0-0089 c.c. per gramme per minute as against 0*003 c.c. during rest. The maximum consumption of oxygen occurred fifteen seconds after the tetanus, and reached the high figure of 0-02 c.c. per gramme per' minute. The character of Verzar's results is shown in the following table :— TABLE XXI. Per cent. Saturation of the Blood. C.c. Oxygen' Used by Muscle. Rate of Blood- Flow per Min. c.c. Venous. Arterial. Per Min. Per Gram. per Min. Normal (resting) . 69 93 i-i6 0-050 -003 Tetanus 33 — 2-40 •178 •010' 15 sees, later 62 — 6-00 -336 ■020 II ,, 60 — 3-52 •208 •012 II ,. ■ 58 94 2-40 •154 0-oog 146 ,1 60 96 o-go 0-059 0-0035 io8 THE PHYSIOLOGY OF MUSCULAR EXERCISE Further, the recent work of Krogh and Lindhard, and of Lind- hard, has furnished data which make it possible to form an estimate of the oxygen-consumption in the muscles of man during exercise. In one experiment, the output of the heart increased fourfold during exercise and the coefficient of utilisation rose from 0"30 to 0'46. Even on the assumption that the distribu- tion of the blood in the body does not alter, this involves a six- fold increase in the amount of oxygen consumed by the muscles. In order to arrive at the actual amount of oxygen consumed by the muscles in man, it is necessary to make two assump- tions, namely, first, that, in a trained healthy man, the muscles form approximately 40 per cent, of the body weight, and second, that, in the resting individual, about one-third of the total consumption of oxygen takes place in the muscles. For the purpose of the calculation, the following data from Lindhard are used. They were obtained in three highly trained individuals : — TABLE XXII. O2 CoDSumpt. per Min. Output of Heart per Min. Coefficient of Utilisation. (I) J. J.; wt. 7S kg. Rest . Work (0) (6) 329 1973 3204 6-0 20-15 35-0 0-30 0-53 0-495 (2) J. L., wt. 63 kg. Rest . Work . 248 2158 4-3 17-85 0-31 0-65 (3) V. M., wt. 64 kg. Rest . Work . 310 2157 5-0 18-05 0-30 0-58 The oxygen-consumption during rest, and the minimum oxygen-consumption during work calculated from these figures are as follows : — Rest. Work. (I) J- J (2)J-L- -, • • (3) V. M. . . . 0-0036 c.c. 0-0032 „ 0-0040 „. 0-0178 (a) c.c. per gram, per min. 0-034 (6) » >. 1. 0-0278 , 0-027 .. .. » ^ When one remembers that, owing to the altered distribution of the blood during exercise, the increase of the blood-flow through , BLOOD-SUPPLY TO THE HEART DURING EXERCISE 109 the muscles may be twice as great as that represented by the minute-volume of the heart, it is clear that during heavy work the consumption of oxygen may be 0*05 c.c. per gramme per minute or even more. It is evident, therefore, that, during severe exercise, the muscles may call for ten to fifteen times as much oxygen as they require during rest, and that they meet this demand by taking up more oxygen from each portion of the blood flowing through them. The additional amount of oxygen which they can obtain in this way is obviously dependent upon the rateof the blood-flow through the muscles. There is probably some de^^ree of adjustment be- tween these two processes, and the muscles may obtain a given quota of. oxygen, either by means of a large blood-supply and a comparatively small coefficient of utilisation or by a large coefficient of utilisation and a moderate increase in blood-supply. But the range of this adjustment is limited, and, during vigorous exercise, the avidity of the muscles for oxygen is such that both a larger coefficient of utilisation and a very rapid flow of blood through the muscles are necessary to satisfy their needs. Although all the circulatory adjustments, discussed in the preceding chapters, contribute to this end, the duty of providing the blood-supply to the muscles primarily devolves upon the heart, and, so long as the output of the heart keeps pace with the work done by the muscles, their functional capacity is fully maintained. The work thrown upon the heart during exercise, however, entails a large increase in the consumption of oxygen by the heart itself, and the ability of the heart to keep up an adequate blood-supply to the brain and muscles during heavy muscular work is conditional upon a corresponding increase in its own blood-supply. The blood-supply to the heart is, therefore, one of the decisive factors which determine a man's capacity to per- form muscular work. The Blood-supply to the Heart During Exercise. The work done by the human heart during heavy muscular work, with an output of 21 litres per minute and an arterial pressure of 130 mm. Hg, may amount to 44*6 kilogrammetres per minute (Evans). If the mechanical efficiency of the heart in these circumstances is assumed to be 25 per cent, (not an unduly 1 1 o THE PHYSIO LO GY OF MUSC ULAR EXERCISE high figure), its consumption of oxygen would be 86 c.c. per min- ute. It is probable that, during extremely severe work, the con- sumption of oxygen by the heart may in some individuals reach lOO C.C. per minute, since an output of 28 litres per minute has been recorded (Lindhard) and the arterial pressure often exceeds that taken as the basis of Evans' calculations. Lewis (191 4) found the weight of the muscular tissue of the two ventricles in normal human hearts to be about 1 50 grammes ; and, allowiijig 50 grammes for the weight of the auricles, the average weight of the muscular, that is to say the oxygen-con- suming, tissue of the human heart is approximately 200 grammes. Its maximum*requirement of oxygen therefore appears to be about 0"5 c.c. per gramme per minute. In all probability, however, a heart, capable of an output of 28 litres, or even of 21 litres, per minute, would be more muscular than the average heart, and pos- sibly the maximum consumption of oxygen by the heart seldom exceeds 0*4 c.c. per gramme per minute. The extent to which the blood gives up its oxygen as it flows through the coronary vessels has not been fully investigated. A few observations made by Evans (191 4), on a heart doing a moderate amount of work, showed a mean coefficient of utilisa- tion of 046, and it is almost certain that, during severe exercise, the coefficient of utilisation for the heart is at least as great as that of the body as a whole, and may reach 0'66 to 07. In that case, a blood-flow of 800 to 850 c.c. per minute through the coronary vessels would enable the heart to take up 100 c.c. of oxygen. Assuming its efficiency to be 25 per cent., its output per minute to be 4 litres, and the arterial pressure to be 100 mm. Hg, the consumption of oxygen by the resting human heart would be about I2'5 c.c. per minute, a figure which agrees fairly well with Evans' estimate of iO"5 c.c. The coronary blood-flow through the heart in a resting man appears to be about 140 c.c. per minute (Starling and Evans). It is clear, that, during heavy muscular work, the oxygen-requirements of the heart may undergo an eight or ninefold increase, and that a sixfold increase in the blood- flow through the coronary vessels is necessary. Two questions therefore arise. First, by what means can the blood-supply to the heart be increased, and, second, are these means equal to the task imposed upon /them? BLOOD-SUPPLY TO THE HEART DURING EXERCISE in The factors which control the blood-flow through the coronary vessels have been investigated for the dog's heart by Evans and Starling (19 13) and by Markwalder and Starling (191 3). Evans and Starling showed that the blood flowing along the coronary vessels reaches the right auricle, partly along the coronary sinus and partly along the vein of Thebesius and other small veins, and that approximately three-fifths of the total blood-flow through the coronary system escapes along the coronary sinus. Having established this fact, they proceeded to measure directly the blood-flow from the coronary sinus in the heart-lung prepara- tion, and 'the figures which they obtained, when multiplied by the factor f, gave the total blood-flow through the coronary system. Similar observations by Markwalder and Starling showed that in different experiments the ratio of the outflow from the coronary sinus to the total coronary flow varied only from o'5i to 0'6 per cent, although, in the different experiments, the total circulation through the heart ranged from 32 to 177 c.c. per minute ; thus the factor | is fairly accurate whatever the rate of the blood-flow through the heart. Making use of these data, they found that the blood-supply to the heart like that to the muscles, is governed by two factors, namely, the arterial pressure, and changes in the tone of the coronary vessels. Broadly speaking, their observations go to show that a rise of 50 per cent, in the arterial pressure may treble the blood-flow through the coronary vessels. TABLE XXIII. Markwalder and Si Arterial Pressure, mm. Hg. ARLING — Output from Coronary Sinus, C.C. per Min. Total Coronary Flow = Sinus Outflow X I, c.c. per Min. 77 96 116 35 63 96 58 105 160 Evans — Arterial Pressure. Total Coronary Flow, c.c. per Mm. Coronary Flow in c.c. per gramme of Heart per Min. Work Done by Heart, kg. per Hour. 80 106 120 39 71-4 1 15 -5 071 1-3 2-1 lO'O 41-4 56-2 112 THE PHYSIOLOGY OF MUSCULAR EXERCISE Since the arterial pressure often rises 50 to 60 mm. Hg during vigorous exercise, this factor alone will greatly increase the coronary blood-flow. Further, the tone of the coronary vessels is markedly lessened by the presence of adrenalin or of metabolic products in the cir- culating blood. Both Evans and Starling and Markwalder and Starling observed that a striking increase in the coronary blood- flow followed the addition of adrenalin to the blood. In one ex- periment (Evans and Starling) in which the arterial pressure was kept constant, the presence of approximately i in 3,000,000 adrenalin in the blood doubled the coronary flow. Similar results have been obtained by Patterson (191 5). The effect of increasing the H • ion concentration of the blood or of an accumulation of metabolic products, such as is induced by asphyxia, is even more marked. On one occasion Evans and Starling found that asphyxia produced a fivefold increase in the coronary flow which, in this instance, reached 37 c.c. per gramme of heart per minute. The susceptibility of the coronary vessels to metabolites is evidently quite as great as that of the arterioles and capillaries in the muscles, and it is probable that, during vigorous exercise, the local concentration of these sub- stances in and around the coronary vessels may bring about a sufficient loss of arteriole and capillary tone to double or more than double the coronary blood-flow. The possibility that, when exercise is carried out under emotional stress, a greater discharge of adrenalin into the blood stream may still further dilate the coronary vessels will be con- sidered subsequently. There seems every reason to believe that, during exercise, the raised arterial pressure, aided by a concomitant decrease in the tone of the coronary vessels, normally ensures a sufficiently large flow of blood through these vessels to meet the needs of the heart, however great these may be. But this is only true so long as the mechanical efficiency of the heart remains high. If its work remains constant, the oxygen-requirements of the heart vary inversely with its mechanical efficiency ; and, if its efficiency declines during exercise, or if it is low from the outset of exer- cise, the heart will expend more energy, and will consume more oxygen, in performing a given amount of work than would a normal heart. It is evident that such a heart, if called upon to SUMMARY 113 perform heavy work, will consume a very large amount of oxygen, and, in these circumstances, its demand for oxygen may exceed the supply provided by the coronary circulation, even though the coefficient of utilisation rises considerably. If this happens, metabolic products will accumulate within the cardiac fibres, thereby bringing about a still further decline in the effici- ency of the heart and limiting its output. Whether this sequence of events ever occurs in the perfectly normal heart, even during very heavy work, is doubtful. But any disturbance of the nutritive condition of the heart lessens its mechanical efficiency (Patterson, Piper, and Starling), and it appears probable that, in a man whose heart is less efficient than normal, the supply of oxy- gen to the heart may become inadequate during exercise, thereby curtailing the range of its output and limiting the capacity of the individual to perform muscular work. Summary. During severe exercise the active muscles may take up from each fraction of the blood flowing through them twice as much oxygen as during rest, and, since the circulation rate is at the same time very rapid, the muscles may consume from ten to fifteen times as much oxygen as during rest. The passage of oxygen from the blood into the tissues takes place solely by diffusion, and the avidity of the active tissues for oxygen is such that the oxygen reaching them at once enters into chemical combination, and their oxygen tension is zero. Consequently the rate at which oxygen can diffuse into the tissues varies directly with the tension of oxygen in the plasma, and this depends upon the extent to which oxyhaemoglobin dis- sociates as the blood traverses the capillaries. During exercise the increased H' ion concentration of the blood in the capillaries of the active muscles and heart leads to more rapid dissociation of oxyhaemoglobin, thereby raising the tension of oxygen in the plasma, and accelerating the rate at which oxygen can pass into the tissues. The work thrown upon the heart during exercise involves a large increase in its expenditure of energy and its consumption of oxygen ; and the ability of the heart to increase its output sufficiently to meet the needs of the brain and muscles is con- ditional upon an adequate supply of blood to the heart itself. 8 114 THE PHYSIOLOGY OF. MUSCULAR EXERCISE It is probable that, during severe exercise, the heart may consume 100 c.c. of oxygen per minute, and that the flow of blood through the coronary vessels may be six times greater than during rest. The increased supply of blood to the heart is brought about partly by the rise of arterial pressure and partly by dilatation of the coronary vessels, and it is concluded that these two factors normally ensure a sufficient coronary blood-flow to meet the needs of the heart for oxygen even during very heavy muscular work. CHAPTER VIII. THE CO-ORDINATION OF THE CHANGES OCCURRING DURING EXERCISE. The Initial Co-ordinating Mechanisms — Later Co-ordinating Mechanisms — Exercise Under Emotional Stress — The Limits of Muscular Exertion. The foregoing analysis of the changes taking place in the circu- latory and respiratory systems during exercise has served to indicate the wide range of the adjustments possessed by these systems and the conditions under which the adjustments are brought into action. But, if the exercise is to be efficiently carried out, something more than the mere existence of these adjustments is required. It is essential that the extent to which they are called into play should be correlated with the activity of the muscular system, and that the supply of oxygen, which is the outcome of these adjustments, should neither outstrip nor lag behind the needs of the body during exercise. In point of fact, such a relationship is normally observed between the amount of work performed and the pulmonary ventilation, the pulse-rate, and the output of the heart (Fig. 8). Some mechanism must, therefore, exist, whereby the activities of the muscles, the nervous system, the heart and the lungs are co-ordinated and linked together in such a way that the resources of the body are utilised to the best advantage and the body acts as a physiological whole. The completeness of this co-ordination is a measure of a man's efficiency as a muscular machine, and any disturbance or failure in this correlation at once lessens the range of his activities. It is necessary then to consider the means whereby this co-ordination is effected. Initial Co-ordination. Foremost among these is the central nervous system, and its influence is most clearly seen at, or even before, the beginning of 115 8* ii6 THE PHYSIOLOGY OF MUSCULAR EXERCISE exercise. The outflow of impulses from the motor cerebral cortex to the muscles is accompanied by a simultaneous outflow to the respiratory, vaso-motor, and cardio-inhibitory centres in the medulla, and there appears to be a very close correspondence between the intensity of the impulses to the muscles and to the medullary centre respectively, so that, for example, when a man starts to run, the immediate increase in his pulse-rate, blood- pressure, and respiration is more marked than if he starts to walk slowly. Voluntary movement, however, is initiated by antecedent psychical processes of the most varied nature and intensity, and these, particularly when' they are mainly emotional, may bring about a rise of blood-pressure, and an increase of pulse-rate and of pulmonary ventilation, which has been termed " anticipatory ". Simultaneously there occurs a toning up both of the muscles and of the whole nervous system, which causes them, so to speak, to stand to attention. These changes are very noticeable in a runner who is waiting for the signal to start in a race. Further, there is some evidence (Bainbridge) that the medul- lary centres may be set in action as an anticipatory process even without the intervention of the higher centres, and that an afferent impulse, for instance, one which evokes pain, may lead to a reflex movement, and may at the same time bring about changes in the respiration, pulse-rate, and blood-pressure almost before the individual is consciously aware of the stimulus, and certainly before the higher centres could affect the medullary centres. This may often be seen during anaesthesia, when the higher centres are presumably out of action, and although the sensory stimulus is not strong enough to call forth a reflex movement (Fig. i8). A similar correlation is probably evoked in ordinary life when movement is brought about unexpectedly in response to afferent stimuli. Another illustration of the anticipatory nature of the respira- tory and circulatory adjustments is afforded by the well-known influence of violent emotion upon the medullary centres, even though, by an effort of will, any voluntary expression of the emotion is checked. Cannon (1915) has suggested that these anticipatory eff"ects are brought about by an outpouring of adrenalin into the circulation ; but, apart from the fact that adrenalin is not known to increase the respiratory movements, the onset of the circulatory and respiratory changes is often INITIAL CO-ORDINATION 117 too abrupt to be accounted for in this way. The almost in- variable occurrence of these respiratory and circulatory changes, under the conditions just described, is evidence of a rather remarkable correlation between the nervous system and the nutritive requirements of the muscles. It may perhaps be re- garded as one aspect of generally heightened activity of the nervous system during muscular exercise. Fig. 18. — Shows the rapid response of the respiratory, vaso-motor and vagus centres to a weak sensory stimulus. The effect of the initial changes is to provide for an increased supply of oxygen to the muscles, brain, and heart from the out- set, and at a time when the other mechanisms, which regulate the respiratory movements and the minute-volume of the heart, have not yet come into action. The vaso-constriction in the splanchnic area, of which the raised blood pressure is the out- ward sign, at once causes more blood to be sent to the skeletal muscles, to the heart, and to the brain. The greater frequency ii8 THE PHYSIOLOGY OF MUSCULAR EXERCISE of the pulse enables the heart to maintain its output against the rising arterial pressure without undue dilatation, and to increase its minute-volume the moment the venous inflow is increased by the more rapid return of the blood to the heart ; and the deeper breathing, in addition to increasing the supply of oxygen, must tend to bring about a larger venous inflow to the heart. Krogh and Lindhard (191 3) find that the output of the heart does not begin to increase until two to three seconds after the beginning of exercise, but it seems possible that this interval may be shortened when the respiratory and circulatory changes just described have taken place before the actual onset of exercise. As Krogh has pointed out, the needs of the active muscles for oxygen increase before there is time for the additional carbonic acid formed by them to pass into the blood, to reach the respira- tory centre, and to evoke more vigorous respiration and thereby to increase the supply of oxygen to the body. It is for this reason that the nervous mechanism, whereby the ventilation is increased at the very beginning of exercise, is essential at this stage of exercise. Later Co-ordinating Mechanisms. Although the influence of the higher centres upon the medul- lary centres is of paramount importance at the beginning of exercise, it is not easy to estimate how far this outflow of im- pulses from the higher centres to the medullary centres persists throughout the period of exercise, and how far it is supplemented, or even replaced, by other co-ordinating mechanisms of a different character. The difficulty of reaching a conclusion on this point is enhanced by the possibility that, at least during severe exercise, the vaso-motor centre may be directly stimulated by a rise in the C„ of the blood, and that even a slight deficiency in the supply of blood to the brain during exercise would aff"ect not only the vaso-motor, but also the respiratory, centre. But the arguments brought forward in the earlier chapters lead on the whole to the conclusion that the higher centres do send out a continuous stream of impulses, not only to the skeletal muscles, but also to the medullary centres, throughout exercise, and that the co-ordinat- ing action of the central nervous system is not confined to the initial stage of exercise. At the same time, other mechanisms play a large, and often LATER CO-ORDINATING MECHANISMS 119 predominant part in co-ordinating the activity of the rest of the body with that of the skeletal muscles during exercise. Krogh and Lindhard (1917) have found, for example, that, during in- duced muscular work, the increase in the pulmonary ventilation, in the output of the heart per minute, and in the pulse-rate, may be quite as marked as that produced by voluntary exercise of equal intensity. In their experiments, the muscles of the legs and back were thrown into activity by electrical stimulation, and the presence of some degree of reflex excitation of the medullary centres cannot be altogether excluded. But, as the outcome of these experiments, Krogh and Lindhard draw the conclusion that (after the initial phase is over) the pulse-rate and the minute-volume of the heart are mainly regulated by some chemical mechanism, whether the muscular work is induced or voluntary. The H' Ion Concentration of the Blood. It is obvious that, so far as the respiratory centre is concerned, the H" ion concentration of the arterial blood must be of the ut- most importance in correlating the activity of the muscles with the pulmonary ventilation, since it is the only stimulus to the respiratory centre. And the question naturally arises, does the increased €„ of the blood during exercise also furnish the means whereby the circulatory adjustments are correlated with the activity of the muscles? Boothby (1915) believes that the answer is in the affirmative, and that the circulation rate, like the pulmonary ventilation, is directly related to the H- ion con- centration of the blood. He considers that " the same regula- tory factor — the C„ of the arterial blood — controls with equal delicacy the ventilation of the lungs and the rapidity of the circulation rate. If we assume that the same regulatory factor governs both processes, it is only necessary to show a cor- respondence between the two processes to estimate the delicacy and sensitiveness of what may be looked upon as a ' centre ' governing the circulation." Boothby thinks it possible that the circulatory centre forms a part of the respiratory centre, and that this performs the double function of controlling both the respira- tion and the circulation. Although the coincident occurrence of two processes under I20 THE PHYSIOLOGY OF MUSCULAR EXERCISE similar conditions does not in itself prove that they have a common origin, its simplicity renders this hypothesis very attrac- tive ; and Boothby points out that, during the apnoea which follows forced breathing, the circulation rate is also slowed, so that here again there is a correspondence between the pulmonary ventila- tion and the circulation rate. Before accepting this view, how- ever, it is necessary to consider whether the many factors which influence the circulation rate are, or can be brought, under the control of such a circulatory centre. The circulation rate through the body as a whole is deter- mined by the output of the heart per minute, and this again depends partly on the venous inflow during diastole, and partly on the ability of the heart to deal with this inflow by trans- ferring blood from the venous to the arterial side of the vascular system. The increased venous inflow to the heart during exer- cise, though aided by the more vigorous respiratory movements, is due mainly to the mechanical action of the active muscles which drive the blood back to the heart. In this way the muscles act as a second pump; and the combined action of the heart, which drives blood into the arterial system and into the blood- vessels of the muscles, and of the active muscles which rapidly return blood to the heart, results in a large acceleration of the circulation rate round the body. Further, the rise of venous pressure, which plays so important a part in regulating the diastolic filling and output of the heart, and in correlating the frequency of the pulse with the rate of filling of the heart, is also due to mechanical factors, and it is difficult to imagine any means by which a medullary, circulatory centre (activated solely by the Ch of the blood) could directly control the venous inflow to the heart. Again, the response of the heart to an increased venous in- flow is governed primarily by the "law of the heart," which is the expression of an .inherent property of cardiac muscle, and is independent of any nervous influence. Indeed, granting that, as the outcome of the mechanical action of the muscles in return- ing blood to the heart, the venous inflow to the heart is propor- tional to the activity of the muscles, the output of the heart per minute will vary directly with the amount of muscular work, so long as the work is not excessive and the heart remains mechanic- ally efficient, and this without the intervention of any nervous LATER CO-ORDINATING^ MECHANISMS mechanism other than reflex acceleration of the pulse in response to diastolic distension of the heart. The pulse-rate, however, is entirely under the control of the cen- tral nervous system, and it might be expected that, if a medullary, circulatory centre does exist, the closest relationship would be observed between the H" ion concentration of the blood and the pulse-rate. But the available evidence (p. 72) goes to show that, when extraneous factors are excluded, changes in the C„ of the blood, so long as these are within small limits, are with- out influence upon the frequency of the pulse, and that the altered reaction of the blood is not the primary cause of the normal correspondence between the activity of the respirato^r and circulatory mechanisms. Further, the fact that the pulmon- ary ventilation and the pulse-rate do not always show a parallel increase during exercise (Means and Newburgh) is against the^r being controlled by a single centre, whose activity is arouseSd by the €« of the blood. This discrepancy removes the main argument on which rests the conception that the frequency of the pulse is regulated during exercise by the reaction .of the blood. '^-■^ - It is true that, as a rule, the relationship between the con- sumption of oxygen and the pulse-rate is extremely close. Even a change of position from lying down to sitting or standing up has a definite effect on both the consumption of ^^gen and the pulse-rate, as the following table shows : — TABLE XXIV.- -Influence of Attitude upon the DICT AND CaTHCART's -RATE. (From Bene- (i) Lying SittiQ (2) Lying on couch Sitting on ergometer (3) Lying on couch Sitting on ergometer But this is fully explainfepjon the assumption that the greater outflow of impulses from . ^fe cerebral cortex to the skeletal muscles, when an individue^t sits or stands up instead of lying 122 THE PHYSIOLOGY OF MUSCULAR EXERCISE down, is accompanied by a similar outflow to the medullary centres, identical in nature with, though less in extent than, that occurring at the outset of ordinary exercise. The conclusion seems inevitable that the output of the heart per minute, and, therefore, the circulation rate, is the resultant of processes most of which cannot be brought under the control of any single nervous centre, and this constitutes a grave ob- jection to the acceptance of Boothby's hypothesis in its present form. All the evidence goes to show that, partly in virtue of the law of the heart, partly by increase of the pulse-rate in response to diastolic distension of the heart, the output of the heart per minute automatically increases with the venous inflow. Consequently, the correlation between the work done by the muscles and the output of the heart can be effected by a purely mechanical process, namely, the rate at which blood is driven from the active muscles back to the heart. There is no doubt, however, that the H- ion concentration of the blood is one of the means by which the supply of oxygen to the muscles is brought into relation with their needs during exercise. But the greater C„ of the blood produces this effect mainly through its direct action on the tone of arterioles and capillaries and on the rate of dissociation of oxyhaemoglobin, and only to a limited extent through the intermediation of the central nervous system. An adequate increase in the local H • ion concentration of the blood flowing through the active muscles will simultaneously lessen the tone of their arterioles and capillaries and increase the rate at which the blood gives up its oxygen to the muscles ; and a sufficient rise in the C„ of the arterial blood will stimulate the vaso-motor centre and tend to raise the mean arterial pressure. These processes bring about a larger flow of blood through the active muscles thereby enabling them — by their mechanical action — to increase still further the venous inflow to the heart, and its output per minute. As the outcome of this concerted action, the circulation rate as a whole becomes more rapid, the blood gives up more oxygen to the tissues, and the effectiveness of almost all the factors con- cerned in increasing the supply of oxygen to the active muscles is enhanced. The rise in the H' ion concentration of the blood required to bring about the changes is not known with certainty, but it is obvious that, wheh once this point is reached, these LATER CO-ORDINATING MECHANISMS 123 changes will be accentuated by every further rise in the local or general H" ion concentration of the blood. There is reason to believe that the H- ion concentration of the arterial blood corresponds fairly closely with the severity of the exercise (Boothby, Douglas, and Haldane) ; and probably this also holds good for the local H • ion concentration of the blood in the vessels of the active muscles and of the heart. Consequently, the H' ion concentration of the blood must contribute considerably, in the way just described, to the correlation of the circulation rate and of the supply of oxygen to the muscles with the degree of muscular activity. It is evident, then, that, during exercise, the co-ordination of the activity of the muscles with the circulatory and respiratory adjustments, which is necessary for the efficient performance of muscular work, can be effected to a large extent by changes initiated by the muscles themselves. Hence, partly by their mechanical action, partly by increasing the local (and general) H • ion concentration of the blood, the skeletal muscles regulate their blood-supply in accordance with their needs. The co-ordination brought about by these processes furnishes, however, a comparatively coarse adjustment, since they prob- ably do not bring into action the vaso-motor and vagus centres until the H' ion concentration of the blood and the venous pressure respectively have risen appreciably. A further and more delicate adjustment between the activity of the skeletal muscles and that of the medullary centres is required, in order to maintain, on the one hand, an adequate blood-pressure for the nutritive requirements of the heart and brain, and, on the other hand, the correlation between the venous inflow and the pulse-rate which is necessary to keep up the mechanical efficiency of the heart. This is effected through the intervention of the higher centres, and every outflow of impulses from the cerebral cortex to the muscles is accompanied by a correspondingly large outflow to the medullary centres and thence into the sympa- thetic system. These impulses, by rendering the respiratory « system more excitable and b^ stimulating the vaso-motor centre, do away with the need for more than a trivial rise in the H" ion concentration of the blood ■•'.and, by lessening the tone of the vagus centre, they permit the necessary acceleration of the pulse to occur with a moderate increase in^venous pressure. 124 THE PHYSIOLOGY OF MUSCULAR EXERCISE Since both their mechanical action on the return of blood to the heart and the H' ion concentration of the blood vary auto- matically with the degree of activity of the muscles, and since a similar relation almost certainly holds between the intensity of the impulses passing respectively to the skeletal muscles and to the medullary centres from the cerebral .cortex, it is clear that all the co-ordinating mechanisms at work during normal exercise are directly connected with the work performed and are ulti- mately dependent on the activity of the motor cerebral cortex. Although artificially induced movement can be carried out fairly efficiently, the co-operation of the higher centres appears to be necessary not only for the complete co-ordination of the activity of the muscles with that of the body as a whole, but also for the full development of the beneficial effects of exercise. The controlling influence of the higher centres is present at every stage of exercise, though it is seen most clearly at the outset of exercise and during emotional stress ; and the ability of a man to make the fullest and most efficient use of his muscles is deter- mined by the accuracy with which this higher co-ordination is effected. A man's nervous organisation is as important as the size of his muscles, and his muscular development is by no means the only criterion of a man's capacity for muscular exertion. An illustration of this truth is found in the greater efficiency, and lessened sense of effort, with which a man performs muscular work when this is done under the stimulus of interest or is ac- companied by pleasure. Conversely, the influence of boredom or of " staleness " upon the amount of exertion which an athlete can make is well known ; and the striking differences, which may occur on successive days, in the performance of a man training for a race, must be attributed almost entirely to variations in the extent to which the nervous system is co-ordinating his muscular movements with the adjustments of the respiration and circula- tion.' It is partly for this reason that a man often runs or rows so much better in a race than in practice. Exercise Under Emotional Stress. The importance of the part played by the higher centres in co- ordinating and integrating the activity of the skeletal muscles and the adjustments of the circulatory and respiratory systems during exercise is most strikingly evident when the exercise is EXERCISE UNDER EMOTIONAL STRESS 125 carried out under emotional stress. Every one is familiar with the fact that, in these circumstances, a man may perform feats of strength or endurance of which he would usually be incapable. For example, McDougall quotes a story of an athlete who, when pursued as a boy by a savage animal, leaped over a wall which he could not again clear until he reached his full growth ; and instances of intense and prolonged exertion, such as the dances of dervishes, carried out under the stimulus of religious or military enthusiasm, abound in literature. Again,, it is a frequent experience of athletes that, when they are apparently exerting themselves to the utmost limit of their powers, a sudden emotional stimulus, such as the shouts of spectators, enables them to develop an unexpected reserve of strength. The supreme muscular efforts occurring under these conditions are only possible if they are accompanied by a corresponding increase in the blood-supply to the muscles, the heart, and the brain. For this purpose, a stronger outflow of impulses to the medullary centres, concomitantly with that to the muscles, is necessary to bring aboqt a sufficient increase in pulmonary ventilation, and to enable the heart to cope with the work thrown upon it. From this point of view, the striking augmentation of cardiac accelerator tone is especially valuable since, as Gaskell showed, stimulation of the sympathetic supply to the heart not only accelerates the pulse but increases the contractile power of the heart ; and a considerable accession of accelerator tone has been observed during severe exercise (Gasser and Meek, 1914). In this way, when exercise is performed under the stress of emotion, the higher arterial pressure, brought about by greater activity of the vaso-motor centre, improves the flow of blood to the muscles, the heart, and the brain ; and the better contractile power and greater frequency of the heart, induced by stronger accelerator and augmentor impulses, enables the heart to increase its output per beat and per minute, and thus to deal with the larger venous inflow following upon the more intense muscular exertion. Nor is the influence of emotion limited to the vaso- motor and vagus centres, since there is a concomitant outflow of impulses along the greater part of the visceral sympathetic system ; and these impulses, by bringing about dilatation of the coronary vessels and a greater discharge of glucose from the liver into the blood, will contribute still further to the working efficiency of 126 THE PHYSIOLOGY OF MUSCULAR EXERCISE the body during exercise. Thus the mobilisation of the reserves of energy in the body during emotional stress finds expres- sion, partly in a simultaneous and proportional increase in the muscular movements, and partly in a stronger discharge of impulses to the medullary centres and along the visceral sym- pathetic system. During the last few years, however, the view has steadily gained ground that a more rapid passage of adrenalin into the blood-stream during states of violent emotion ijot only occurs, but is the essential factor in enabling the individual to extend the range of the exertion of which he is capable ; and some writers appear to regard the action of adrenalin as replacing, rather than supplementing, the outflow of impulses from the brain along the sympathetic system. According to this view, which has been vigorously advocated by Cannon (191 5), adrenalin is thrown into the blood-stream just at the moment when its stimulating influence on the circula- tion, the liver, and the muscles will increase the functional capacity of the muscles and heart sufficiently to enable them to meet the additional demands made upon them by the nervous system. It serves, therefore, both to supplement and to reinforce the co-ordinating processes ordinarily at work during exercise ; and, just as the accelerator of a motor-car, at a touch from the driver, increases the supply of petrol to the engine, when the latter is required to do more work, adrenalin, suddenly entering the blood-stream in response to an impulse from the central nervous system, increases the oxygen-supply and consequently the functional capacity of the whole body. The Action of Adrenalin. Before entering into any discussion of this view it will be convenient to consider briefly some of the effects of such a dis- charge of adrenalin into the blood-stream, assuming it to occur. As regards its action upon the heart, Evans (191 4, 1917) has recently confirmed and extended the earlier work of Barcroft and Dixon (1907), who found that the expenditure of energy by the isolated heart, as measured by its consumption of oxygen, was greatly increased by the addition of adrenalin to the blood. An example of Evans and Ogawa's results is shown in the following table : — EXERCISE UNDER EMOTIONAL STRESS 127 TABLE XXV.— (Evans and Oqawa.) Pulse-Rate. Output Litres per Hour. C.c. 0.^ Used by Heart per Hour. Kgm. Work Done. Efficiency. 46 67-86 II-5 "•5 58 176 I7"5 17-5 14-6 No adrenalin. 4-8 Adrenalin added. The larger consumption of oxygen is not simply the result of greater frequency of the pulse, since a similar or greater change in pulse-rate, brought about by raising the temperature of the heart, increases the consumption of oxygen to a much smaller extent ; and Evans concludes that adrenalin directly stimulates the metabolic processes in the cardiac muscle fibres, and increases the energy developed at each heart-beat. Hence, for any given diastolic volume of the heart, more energy is set free during the succeeding systole when adrenalin is present than when it is absent, or to express the same fact in another way, the presence! of adrenalin enables the heart to develop a given amount 'of | energy with a smaller diastolic volume. Von Anrep (i9i2)Ti^s shown that, under experimental conditions, this is actually the case. One result of its diminished volume is to extend the range of dilatation of the heart, and to enable the heart to increase its expenditure of energy still further, if it is called upon to perform more work. Adrenalin, then, calls out the reserve-force of the heart, and adds to its power to mobilise its stores of energy. This effect is presumably produced through its action upon the endings of the sympathetic fibres to the heart, since Gaskell long ago proved that stimulation of the sympathetic supply to the heart leads to a similar augmentation of its contractile power. Further, as Patterson (191 5) has shown, adrenalin shortens the systole, both absolutely and also relatively to the diastolic period ; at the same timte it intensifies the contractile stress, and the rate at which this develops during systole, with the result that the endocardiac pressure is high and the blood is expelled more forcibly into the aorta. These changes enhance the power of the heart to maintain its output against a high arterial pressure. There is no doubt, therefore, that a sudden addition to the 128 THE PHYSIOLOGY OF MUSCULAR EXERCISE circulating blood of sufficient adrenalin to bring about the changes just described will be advantageous to the circulatory system in every way. In the first place, partly by accelerating the pulse and partly by improving the contractile power of the heart- muscle, adrenalin extends the range of the output of the heart per minute, and enables it to deal with a larger venous inflow than would otherwise be possible. If a man is doing such heavy work that the output of his heart is almost at its maximum, a sudden inflow of adrenalin into the circulating blood, occurring coincidently with a greater muscular effort, will permit of a corresponding' increase in the output of his heart. At the same time, the greater and more quickly developed endocardiac pressure evoked by adrenalin enables the heart to maintain this output in, spite of the raised arterial pressure. In the second place, the concurrent rise of arterial pressure, brought about mainly by the action of adrenalin on the splanchnic arterioles, increases the blood-supply to the brain, and to the muscles. Finally, adrenalin brings about a larger coronary blood-flow, not only by raising the blood-pressure, but also by dilating the coronary vessels. Whether adrenalin has any direct effect upon skeletal muscle, apart from that brought about by increasing its blood-supply, is uncertain. Oliver and Schafer (1895) stated that the contraction of isolated frogs' muscle was prolonged in the presence of supra- renal extract, but Schafer has since shown that adrenalin itself does not produce this effect. More recently, Cannon and Nice found that the contractile power of fatigued muscle was im- proved by an intercurrent stimulation of a splanchnic nerve, and drew the conclusion that this was due to a direct action of adrenalin upon skeletal muscle. They obtained the same result when adrenalin was injected into the blood-stream. This ob- servation was confirmed by Gruber, who states that it is not due merely to an improved blood-supply to the muscle, since, even when the muscle is perfused with Ringer's solution, the addition of adrenalin improves the contractile power of fatigued muscle, although the flow of fluid through the muscle decreases. Gruber concludes that adrenalin has a twofold action on muscular con- traction, one by improving its blood-supply, the other depending upon its chemical action upon the muscular fibres. Further observations are desirable, however, on this question. EXERCISE UNDER EMOTIONAL STRESS 129 The Part Played by Adrenalin During Exercise. If a sudden discharge of adrenalin from the suprarenal glands is to occur when it is most useful, namely, during exercise carried out under emotional stress, this must be controlled by the central nervous system. That adrenalin might pass in larger amount into the blood-stream as a reflex response to certain afferent impulses was first suggested by the observation of Cannon and de la Paz (19 10) that the adrenalin content of the vena caval blood was increased in cats during emotional excitement induced by the barking of a dog. In 191 1, Cannon and Hoskins found that a similar increase occurred during the excitement stage of anaesthesia, or as a result of stimulation of sensory nerves. In 1 91 2, Elliott showed that, in cats, emotional excitement, anaes- thetics, and the stimulation of sensory nerves, lessened the adrenalin content of the suprarenal gland if this retained its normal connection with the central nervous system, but not if it was isolated from the nervous system. Elliott concluded that emotion leads to a more ra/ x^l 200 400 600 800 IGOO 1200 1400 1600 1800 2000 Oxygen Consumption:c.c.per Minute. Fig. ig. — (Constructed from Lindhard's data.) A = untrained subject, B = trained subject. The oxygen consumption indicates the severity of the exercise. "BABLE XXX.— (LiNDHARD.) Non-athlete. Athlete. Rest. Work. Rest. Work. Oxygen-consumption Pulse-rate per minute . Output of heart per min. ., » per beat Coefficient of utilisation Weight of subject 195 c.c. 72 3-9 litres 54-5 CO. 0-31 50 kg. 1051 144 - II-4 79 0-50 3-30 68 4-9 72 0-36 73 kg. I171 c.c. 92 1475 160-3 0-43 It has been shown (p. yy") that the total energy expended in maintaining the output of the heart per minute, whether 144 THE PHYSIOLOGY OF MUSCULAR EXERCISE during rest or during exercise, is the product of the energy set free at each heart-beat, and of the number of beats per minute. Since physical training, by increasing the size (i.e. the muscular C issue of the heart), enables it to develop more energy per beat, t is clear that, if the minute-volume of the heart in the trained and untrained man is the same, the output per beat will be arger, and the pulse-rate less, in the former than in the latter. Further, when the exercise becomes so severe, and the venous inflow so large, that the heart dilates to its physiological limit during diastole, the stronger heart of the athlete will empty itself more completely at each beat than the weaker heart of the un- trained man ; and the maximum output of which the heart is capable will be correspondingly larger. Frequently, however, the output of the heart per minute is less in a trained man than in an untrained man, when they are performing the same amount of work, since the coefficient of utilisation is greater in the trained man. A striking example of this difference is furnished by the following figures : — , TABLE XXXI.— (Krogh and Lindhard.) Work Done: Kgm. Metres. O2 Consumed: c.c. per Minute. Minute- Volume of Heart in Litres. Coefficient of UtiUsaty>n. J. L. trained A. K. untrained , 446 1350 1330 9-8 i6-o 073 0-47 Whether the larger coefficient of utilisation in the trained man is the result of some modification in the rate at which the blood flows through the muscles, or whether the ability of the muscles to take up oxygen from each fraction of the blood flowing through them is increased, is not known. But the larger co- efficient lessens considerably both the strain thrown upon the, heart and the amount of work which it is called upon to perform, thereby adding to the reserve power of the heart and making possible a larger supply of oxygen to the muscles during heavy work. Again, training increases the red corpuscles and the haemo- globin value of the blood (Michell). Schneider and Havens (1915) observed, in one subject, an increase of 9-4 per cent, and, in another subject, an increase of 3-6 per cent, in the haemo- EXERCISE IN THE TRAINED AND UNTRAINED MAN 145 globin value of the blood. The rise is of importance chiefly as an indication of the improved physical condition of the subjects, and it is known that, in men undergoing training, a fall in the hemoglobin value is often a sign of " staleness " or of their being below par. But the greater oxygen-carrying power of the blood must also assist appreciably in lessening the output of the heart necessary to keep up the oxygen-supply to the muscles for any given amount of muscular work. The advantages of training are not confined to the circulatory system, and the mechanical efficiency with which work is per- formed is greater in the trained than the untrained man (Lindhard, Benedict and Cathcart). Biirgi (1900) found that, for the same individual, training reduced the output of carbonic acid from 2,430 to 2,103 c.c. per kilogrammetre of work performed. Zuntz (1903) showed that a dog, trained for one form of exercise, carried this but more efficiently than another form of exercise to which it was unaccustomed, and concluded that the muscles actually employed in any particular kind of exercise work more economic- ally when trained. These effects are almost certainly brought about mainly through the intermediation of the central nervous system, with the resi^ that the co-ordination and adjustment of the movements involved in any form of exercise is more per- fectly effected and useless movements of other muscles are elim- inated. Thus the trained man can perform a given amount of work with a smaller consumption of oxygen and a smaller output of carbonic (and lactic) acid than the untrained man. The smaller consumption of oxygen lessens the output of the heart necessary to provide an adequate supply of oxygen to the muscles ; and the decreased output of carbonic (and lactic) acid leads to less change in the €„ of the blood in the trained, than in the untrained, man for the same amount of external work. It seems probable, too, that the smaller muscular effort necessary for the performance of a given amoufit of work in the trained, as compared with the untrained, man is associated with a lessened outflow of impulses from the higher centres, not only to the muscles, but also to the medullary centres ; and this, if it occurs, will tend to keep down both the pulse-rate and the blood- pressure. Training leads, then, to increase of power and economy of 10 t46 THE PHYSIOLOGY OF MUSCULAR EXERCISE effort, and the trained man is better equipped at almost every point to perform muscular work than is the untrained man. By developing his skeletal muscles, his heart, and his lungs, training extends very greatly th'e range of the exertions of which a man is capable ; and, by bringing about better co-ordination of his movements, it enables a man to take moderate exercise with a minimal expenditure of energy and with scarcely any sense of effort. Nor are the advantages conferred by training purely physical, since the sense of strength and well-being, which it usually engenders, colours and reacts upon the individual's out- look and actions as a whole. Second Wind. The transition, during vigorous exercise, from a state of respiratory and, to a less extent, of cardiac distress to one in which the individual breathes easily and comfortably, and feels able to continue the exercise almost indefinitely, is known as getting one's " second wind," and is a familiar event in the experi- ence of most people. But the conditions under which it usually occurs render investigation and analysis of its real nature very difficult. Indeed, beyond the facts that the transition may be gradual or may be fairly abrupt, and that it takes place both in the trained and in the untrained man, very little is known about it. The only observations which throw any light on it are those of Pembrey and Cooke (191 3). They found that, dur- ing the period of laboured breathing before second wind, the pulmonary ventilation and the percentage of carbonic acid in the alveolar air were higher than after second wind had occurred (Table XXXII.). Further, while the onset of second wind was not accompanied by any constant change in the pulse-rate or the arterial pressure, they noted a close association in time between the onset of sweating and of second wind. The only possible explanations of the decrease in the pulmon- ary ventilation, as second wind supervenes, are either a fall in the H • ion concentration of the blood reaching the respiratory centre, or a diminution in the excitability of the respiratory centre ; and the latter possibility would appear to be excluded by the fact that the alveolar tension of carbonic acid falls concomitantly with the pulmonary ventilation. Pembrey and Cooke's observations, while pointing clearly to the conclusion that the H" ion concen- SECOND WIND TABLE XXXII.— (Pembrey and Cooke.) 147 Alveolar Air. R.Q. Respiration. CO2 Volume per Cent. Og Volume per Cent. Volumes Breathed at 17° C. in Litres per Minute. Rate. (i) Rest .... After running 9 laps, Dyspnoea After running 13 laps second wind had 5'9I 7-55 13-85 14-07 o-8o i-io 8-5 35'S 12 21 supervened 577 13-63 074 19 22 (2) Rest .... 8 21 Dyspnoea ; 8 laps Second wind ; 16 laps 32 laps = I mile. — 23 i8-5 37 26 tration of the blood falls during the establishment of second wind, throw no light on the means by which this is effected ; and, although, from time to time, various suggestions have been offered in explanation of this fall, none of them appears to have been put to the test of experiment. Some discussion of these suggestions is, however, not altogether unprofitable, since the processes which regulate the H- ion concentration of the blood are much better understood than was the case a few years ago. In considering the causation of second wind it is of impor- tance to bear in rrlind the fact that second wind, when once es- tablished, tends to persist through the period of exercise, even though this becomes more severe. This fact suggests very forcibly that the fall in the H- ion concentration of the blood is the outcome of some process or processes which remain effective throughout the exercise, and that a state of equilibrium is set up between the factors which tend respectively to raise and to lower the H* ionxoncentration of the blood. It is possible, therefore, that second wind may be brought about by the interaction of a variety of mechanisms, and even that the relative importance of these mechanisms in its production may not be the same in all individuals. The fall in the H" ion concentration of the blood may result either from a lessened production of lactic and carbonic acid in the active muscles, or from more rapid removal of these acids from the blood, or from more rapid oxidation of lactic acid. In favour 148 THE PHYSIOLOGY OF MUSCULAR EXERCISE of the first possibility is the observation that, owing to the elimi- nation of unnecessary movements and improved co-ordination of the active muscles, exercise is carried out more efficiently as the exercise proceeds, and that the individual does the same amount of work with a smaller expenditure of energy. A man, in fact, takes a little time to " get into his stride ". In so far as this occurs it will tend, by lessening the total pro- duction of acid in the muscles, to minimise the rise in the €„ of the blood during exercise. The gradual rise of the temperature of the body early in exercise also leads, as has been pointed out (p. 20), both to greater efficiency of the muscles and to more complete oxidation of lactic acid within the muscles themselves, and must contribute in this way to a gradual fall in the amount of this acid escaping from the muscles into the blood. Hence the association between the onset of sweating and that of second wind may perhaps indicate the part played by an adequate rise of the temperature of the body upon the reaction of the blood. The amount of lactic acid entering the blood from the muscles is dependent, however, not only on the rate at which this acid is produced but also on the rate at which it is oxidised in the muscles, and for this latter purpose the supply of oxygen must be sufficient. It is conceivable that, at the outset of exer- cise, the co-ordination between the circulatory adjustments, which provide the supply of oxygen to the muscles, and the activity of the muscles themselves may not be quite perfect, and that, for a short time, the supply of oxygen to the muscles may lag behind their demands. If this happens, the amount of lactic acid passing into the blood may be so great as to lower the alkali-reserve of the blood very rapidly, and to bring about a progressively increasing H' ion concentration of the bloo'd and severe dyspnoea. As soon as the blood-flow through the muscles becomes more ac- curately adjusted to the extent of their activity, less lactic acid will escape oxidation and enter the blood, the reaction of the blood will swing slightly towards its normal level, and the dyspnoea will decline into hyperpncea. Whether, at the begin- ning of exercise, a temporary discrepancy exists between the needs of the active muscles and their blood-supply is not known. But the output of the heart, the blood-pressure, and the pulse-rate rise so early during exercise, and their efficiency in increasing the flow of blood through the muscles is so great, that the occur- SUMMARY 149 rence of such a discrepancy does not appear very probable, except, perhaps, in the untrained man during severe exercise. There is yet another factor which may contribute to the lowering of the H' ion concentration of the blood associated with second wind, namely, an interchange 0/ acid and basic radicles between the blood-plasma and the red corpuscles and tissues. That such an exchange is not only possible, but actually does occur, has already been pointed out (p. 31), and, since the re- action of the blood cannot differ appreciably, except very tem- porarily, from that of the tissues, this interchange must come into play whenever the reaction of the blood alters. The passage of bases into the blood will increase its alkali-reserve, whereas much of the lactic acid diffusing into the tissues (other than the active muscles) is probably oxidised ; and, since the tissues also contain a phosphate buffer-system, which stabilises their reaction, this interchange between the tissues and the blood may account, at least to some extent, for the fall in the H* ion concentration of the blood which brings about second wind. Although direct evidence is lacking, one may surmise that all the processes just discussed may be involved in the causation of second wind ; and its earlier, sometimes almost imperceptible, onset in the trained man may be ascribed to the greater efificiency, not only of his heart and his circulatory adjustments, but also of his muscles and, from the point of view of exercise, of his nervous system. Indeed the very existence of second wind throws into relief the complexity of the regulating processes at work during exercise, and demonstrates the exactness of the co- ordination between its different parts, which is necessary for the smooth working of the, body generally. Summary. Regular and progressive exercise is the essential feature of training, and the character of the diet, provided this is ample and is properly digested, is of subsidiary importance. Training develops not only the skeletal muscles, but also the heart, and, in a healthy man, the development of his, heart cor- responds with that of his muscular system. Owing to the in- crease in its contractile power, the output of the heart per beat is often larger, and the pulse-rate less frequent, in the trained, than in the untrained man, even during rest. ISO THE PHYSIOLOGY OF MUSCULAR EXERCISE When a trained, and an untrained man, take the same amoijnt of exercise, the pulse is less frequent, the arterial pressure is usually lower, and the minute-volume of the heart is smaller in the former than in the latter. These differences are due partly to the fact that the output of the heart per beat is larger in the trained man, and partly to the greater coefficient of utilisation and oxygen-carrying power of the blood in the trained man, which lessen the output of the heart per minute necessary to provide a given supply of oxygen to the muscles. The better co-ordination of movement, which is brought about by training, also improves the mechanical efficiency of the body. The effect of these changes is not only to increase a man's power of doing muscular work, but also to enable such work, whether heavy or light, to be performed with the utmost economy of effort. The characteristic features of "second wind" are a simul- taneous fall in the alveolar tension of carbonic acid and a de- crease in the pulmonary ventilation ; and they are caused, in all probability, by a diminution in the H" ion concentration of the blood. The possible causes of the diminished H- ion concentra- tion of the blood are greater mechanical efficiency of the body, an improved blood-supply to the muscles, and the exchange of acid and basic radicles between the blood and the tissues. Itappears probable that all these processes are concerned in bringing about "second wind". CHAPTER X. EXERCISE AT HIGH ALTITUDES. The Process of Acclimatisation — The Passage of Oxygen into the Blood— The Changes During Exercise. Among the various symptoms of " mountain sickness " a lessened ability, or complete inability, to carry out active physical exer- tion is conspicuous. As acclimatisation to lowered oxygen- pressure takes place, this disability passes off to a consider- able extent ; and a man, who is acclimatised to high altitudes and in good physical training, can, as the experience of mountain climbers shows, perform very severe exercise. But, in all individuals, exercise at high altitudes exhibits two character- istic features. In the first place, the respiratory and circulatory changes produced by a given amount of exercise are greater than at low levels, and, in the second place, the maximum amount of work, which can be carried out by the individual in a given time, is less than at low levels. These features are most notice- able in the unacclimatised subject, and, after acclimatisation has taken place, the response to gentle exercise may scarcely differ at high altitudes from that at low levels ; but, however complete the adaptation may be, they always appear during severe exer- cise. The effects of exercise upon the pulmonary ventilation have been worked out by Douglas, Haldane, Henderson, and Schneider (19 1 2), on Pike's Peak, which is 14,109 feet above sea- level, and are illustrated in the following table : — TABLE XXXIII. — Pulmonary Ventilation in Litres p6r Minute. (At 37° C. Moist and Prevailing Barometer.) (Douglas, Haldane, Hen- derson, AND Schneider.) At Orford. On Pike's Peak. Rest, standing .... Walking 2 miles per hour . >. 4 .. 1. • • .. 5 » .. • • io'4 litres i8-6 „ 37-3 » 60-9 „ 14-89 litres 27-9 .. 57-5 .. IIO-2 „ 151 152 THE PHYSIOLOGY OF MUSCULAR EXERCISE The consumption of oxygen for each grade of exercise was not appreciably different at Oxford and on Pike's Peak respectively. With regard to the circulatory changes, Schneider, Cheley, and Sisco's observations (191 6) show that the acceleration of the pulse and the rise of arterial pressure during exercise are greater at high altitudes than at low levels, and that there is a corresponding delay in the return of the pulse-rate and blood- pressure to the normal after the exercise. Although, in a trained and acclimatised man, these effects are not brought out by walking slowly, they appear during walking at four miles an hour, and become very striking when the exercise consists in rapid running. TABLE XXXIV. — Effect of Exercise on Pulse-rate and Arterial Pressure. (From Schneider, Cheley, and Sisco.) Walking 3 miles/Colorado Springs per hour \Pike's Peak Walking 4 miles/Colorado Springs per hour \ Pike's Peak Short run up-fColorado Springs hill \ Pike's Peak I Resting 'ulse-rate. Arte Resting rial Pressure. Just after Exercise. Just after Exercise. 69 76 71 82 70 85 80 ^ 102 100 132 108-160 206 (average) "3 124 114 116 130 130 112 132 120 142 166 (average) 197 Exercise also causes a greater rise of venous pressure at high altitudes. There is no evidence regarding the output of the heart or the coefficient of utilisation. Lack of oxygen is the cause of the lessened ability of the individual to perform work at high altitudes, and the exaggerated circulatory and respiratory response to exercise is undoubtedly a compensatory process. But, before discussing the causation of these compensatory changes, it is necessary to consider briefly the nature of the processes which constitute acclimatisation. Fortunately for this purpose it happens that most of the more recent investigations have been made at much the same barometric pressure, those of Douglas, Haldane, Henderson, and Schneider ( 1 9 1 2), of Schneider and Sisco ( 1 9 1 4), and of Schneider, Cheley, and Sisco (1916), on Pike's Peak at an average baro- metric pressure of 457 mm. Hg, and those of Hasselbalch and Lindhard (191 5), in a pneumatic chamber at a pressure of 448 to 462 mm. Hg. The results obtained on Pike's' Peak, and in the THE PROCESS OF ACCLIMATISATION 153 pneumatic chamber, agree so closely that the greater intensity of the sunlight, the fall of temperature, and other changes incidental to life on a mountain, clearly do not take any active part in the process of acclimatisation. The Process of Acclimatisation. Tke Respiratory Changes. — After acclimatisation had taken place, the two main respiratory changes observed, both on Pike's Peak and in the pneumatic chamber, were, first, an increase of approximately 50 per cent, in the pulmonary ventilation as com- pared with that at or near sea-level, and, second, a fall in the M.M.CO2 40 35 30 25 to -— i?3 'Tensi *..*. Baror letric \ - \( -^ \ — - - 800 700 « 0. 600 t> "ii a a> 500 e o u 400 "D I 8 10 II 12 : 3 4 5 6 7 Days. Fig. 20. — Influence of barometric pressure upon the alveolar tension of carbonic acid. (Hasselbalch and Lindhard.) alveolar tension of carbonic acid (Fig. 20 and Table XXXV.). The result is that the tension of oxygen in the alveolar air is from 16 to 18 mm. Hg higher than otherwise would be the case. TABLE XXXV. Douglas, Haldane, Henderson, AND Schneider. Hasselbalch and Lindhard. Near Sea-level. Bar. 747- Pike's Peak. Bar. 457. Near Sea-level. Bar. 755. Pneumatic Chamber. Bar. 454. Pulmon. ventilation Alveolar CO2 tension „ oxygen ten- sion . 7-67 litres 39'6 mm. Hg. 100-4 .. I0-29 (Douglas) 26-9 547 5-25 litres 36-3 ,. 8"0 litres 24-4 „ 154 THE PHYSIOLOGY OF MUSCULAR EXERCISE These changes clearly point to the existence of a very slight rise in the H" ion concentration of the blood, but the increase in the pulmonary ventilation is so trivial that the actual altera- tion in the €„ of the blood must be almost inappreciable. Direct observations by the gas electrode method have been made by Hasselbalch and Lindhard (191 5), who find that, at a low barometric pressure, the reaction of the blood is practically unaltered, when it is exposed to the alveolar tension of carbonic acid existing in the subject at that pressure. TABLE XXXVI. — (IJasselbalch and Lindhard.) P„ of Blood. Barometer 760 mm. Hg. Blood exposed to alveolar tension of CO2 = 40-8 mm. Hg Barometer 589 mm. Hg. Blood exposed to alveolar tension of COj = 32'2 mm. Hg Barometer 760 mm. Hg. Blood exposed to COj at 40 mm. Hg. tension Barometer 589 mm. Hg. Blood exposed to CO^ at 40 mm. Hg. tension 7-50 7-48 7-51 7-44 This accords with the evidence of Barcroft, Camis, Mathison, Roberts, and Ryffel (191 5), who have shown that the form of the dissociation curve of haemoglobin hardly alters at an altitude of 10,000 feet. Since the reaction of the blood scarcely differs from normal, whereas the fall in the alveolar tension of carbonic acid is con- siderable, there must necessarily be a decrease in the sodium bicarbonate content of the blood. That this is the case is clear from Hasselbalch and Liridhard's observation (Table XXXVI.) that, when the blood of an individual living at a high altitude is compared with that of the same individual living at sea-level, the two samples being exposed to the same tension of carbonic acid, the former is distinctly the more acid. The same fact is brought out in the experiments of Barcroft, Camis, Mathison, Roberts, and Ryffel in which, testing the blood in the absence of carbonic acid, they observed, by Mathison's method, that it was uniformly more acid at a high altitude. In short, there is, at a high altitude, a simultaneous fall in the alveolar tension of carbonic acid, and in the alkali-reserve of the blood, though, since these two changes almost counterbalance ' THE PROCESS OF ACCLIMATISATION 155 one another, the reaction of the blood scarcely differs from the normal value. Douglas, Haldane, Henderson, and Schneider look upon the fall in the alveolar tension of carbonic acid as secondary to a primary reduction in the alkalinity of the blood. They reject the view that this is brought about by the passage of lactic acid into the blood, since the tension of carbonic acid remains low, even after the symptoms of oxygen-want have almost entirely disappeared. They conclude that the change is due to some adaptive alteration in the regulation of the alkalinity of the blood, and they suggest that an alteration in the reaction of the urine excreted by the kidneys would account for the facts. Barcroft and his co-workers consider that the change in the blood at moderate altitudes is due mainly or entirely to some other cause than lactic acid, whereas, at high altitudes, the amount of lactic acid present in the blood is increased. Their observa- tions at high altitudes, however, were made on the day of their arrival, and before acclimatisation had taken place; it seems doubtful, therefore, whether lactic acid takes any share in reduc- ing the alkali-reserve in the fully acclimatised person during rest. Hasselbalch and Lindhard's interpretation of the facts under discussion is the converse of that just stated. They hold that the primary change takes place, not in the blood, but in the respiratory centre. They believe that, at high altitudes, the respiratory centre becomes abnormally sensitive to the H" ion concentration of the blood, this change bringing about increased pulmonary ventilation and a fall of the alveolar tension of carbonic acid. The lowered tension of carbonic acid must be compensated by a secondary fall in the sodium bicarbonate content of the blood, and Y. Henderson has shown that greater pulmonary ventilation does lower the alkali-reserve of the blood. If such a change in the excitability of the respiratory centre is admitted, it would undoubtedly account for the observed facts, and, in this connection, Hasselbalch and Lindhard's (1916) obser- vation that the amount and percentage (relatively to the total nitrogen) of the urinary ammonia are diminished at high altitudes is very significant. An increase in the ammonia in the urine is one of the recognised means by which the body compensates for a greater production of acid in the body ; conversely, the addition 1 56 THE PHYSIOLOG Y OF MUSCULAR' EXERCISE of alkali to the body is known to decrease the excretion of am- monia. Although Hasselbalch and Lindhard regard the decreased output of ammonia as dependent on some metabolic alteration induced in the tissues by the increased C„ of the blood, it may equally be taken as evidence that more alkali than usual is avail- able in the tissues to combine with the acid formed in the body and that, in consequence, less ammonia is required for this purpose. The possibility that the excitability of the respiratory centre might be greater at high altitudes had previously been rejected by Haldane (191 2) on the ground that it would diminish, and not increase, the supply of oxygen to the tissues. He supposed that the dissociation curve of oxyhaemoglobin would be shifted to the left, and that the blood would therefore dissociate less readily and completely than usual during its passage through the capillaries. But the fact that the dissociation curve of blood is practically unaltered in form, and that such shift as does occur is towards the right (Barcroft and his co-workers, 1914), seems to dispose of this objection. Hasselbalch and Lindhard believe that the greater sensitive- ness of the respiratory centre is a direct result of the lessened tension of oxygen in the blood, and Haldane and Poulton's ob- servation (1908) that oxygen- want produces this effect, probably by bringing about a greater production of acid within the centre itself, seems to offer an adequate explanation of such a change. In the resting individual, it is the nervous system, and not the muscles, which is most readily affected by lack of oxygen ; and such a lack, while too slight to increase the passage of lactic acid into the blood from the muscles, might well lead to a sufiScient forma- tion of acid in the nervous system to heighten the excitability of the respiratory centre. In that case the greater pulmonary ventilation, by raising the alveolar tension of oxygen, would enable the blood to' become sufficiently saturated with oxygen to maintain an adequate supply both to the brain and to the body as a whole. Thus, in the process of acclimatisation, a position of equilibrium would be reached, at which the pulmonary ventila- tion would be just sufficient to keep the production of acid in the respiratory centre from exceeding the minimal level necessary to ensure an adequate ventilation. Such a process is certainly more intelligible than an adaptive alteration on the part of the THE PRO CESS OF A CO LIMA TISA TION 157 kidney since, so far as is known, the kidney blindly responds to every change in the reaction of the blood, and there is no evi- dence that it initiates such changes. Hasselbalch and Lindhard (19 1 6) have determined the P„ of the urine during the process of , acclimatisation ; but their results show no significant alteration from the normal P„ value. Whatever its cause may be, the increased pulmonary ventila- tion raises the tension of oxygen in the alveoli, at 457 mm. Hg barometric pressure, from 35*8 mm. Hg to 52 to 55 mm. Hg. Taking the dissociation curve of Barcroft's blood as a standard, this means that the haemoglobin of the blood as it leaves the lungs may be 86 per cent, saturated with oxygen instead of 65 per cent, saturated. Since the haemoglobin value of the blood in a fully acclimatised man may be from 1 20 to 1 30, and occasion- ally as high as 1 50 (Douglas, Haldane, Henderson, and Schneider), it is evident that the amount of oxygen reaching the tissues may be greater than at low levels, and that a resting, acclimatised man may be over-compensated. The Circulatory Changes. In confirmation of earlier observers (Zuntz, Durig, and Kolmer), Douglas, Haldane, Henderson, and Schneider, and also Schneider and Sisco, find that, on Pike's Peak, the pulse- rate, even after acclimatisation, is greater than at low levels. The individual variations are considerable, some men showing acceleration of only a few beats, and others an increase of ten beats or more ; in exceptional cases the acceleration may be replaced by a decrease in pulse-rate. The systolic arterial pres- sure is practically unchanged, but Schneider and Sisco record a lower venous pressure on Pike's Peak than at low altitudes ; and they attribute the fall of pressure to the increased pulse-rate. These changes persist even after complete acclimatisation, as is shown by the following figures obtained in one of their subjects, who spent six months in each year on Pike's Peak, and six months at Colorado Springs : — 158 THE PHYSIOLOGY OF MUSCULAR EXERCISE TABLE XXXVII. Average Pulst-rate. Arterial Pressure : Venous Pressure Cm. Water. Systolic. Diastolic. Mm. Hg. Colorado Springs (6,c(oo feet) . Pike's Peak (14,109 feet) 71 87 116 110 83 83 13-6 g-9 The output of the heart per minute appears to be practically the same at high as at low levels. The methods used by Douglas, Haldane, Henderson, and Schneider for estimating the output per beat were first, the pulse-pressure, and, second, the recoil board devised by Yandell Henderson. Both these methods indicate that the output per beat is diminished on Pike's Peak, but that, owing to the acceleration of the pulse, the minute-volume of the heart is the same as at Colorado Springs. Schneider and Sisco (191 4) have measured the rate of blood-flow by Stewart's method, which consists in determining the amount of heat given off by the hand in a certain time, the hand being immersed in a water calorimeter. They found that the circulation rate through the hands was from 30 to 76 per cent, greater on Pike's Peak than at low levels, and, since their observations with the recoil board indicated a larger output of the heart per minute, they concluded that the circulation rate as a whole was more rapid. Hasselbalch and Lindhard, however, employing Krogh and Lindhard's method, have found that the output of the heart is not increased at high altitudes during rest, thereby confirming Douglas, Haldane, Henderson, and Schneider. In a later paper, Schneider and Sisco (191 4) attribute the increased blood-flow through the limbs partly to dilatation of the arterioles and partly to greater rapidity, of the circulation as a whole, this being brought about by acceleration of the pulse and fall of venous pressure. But, as has been pointed out (p. 65), acceleration of the pulse increases the circulation rate only in so far as it increases the output of the heart, and, during rest, the diastolic filling of the heart is so slow that increase in the pulse-rate usually has no influence on its output. The fall of venous pressure, again, is merely an incidental sequence of the greater frequency of the pulse, and does not in itself indicate any THE PASSAGE OF OXYGEN INTO THE BLOOD 159 change in the circulation rate as a whole. It must be concluded, then, that, at high altitudes, the circulation rate is the same as at low levels, and that the greater blood-flow through the limbs is due to dilatation of the limb-vessels. Since the arterial pressure is practically unaltered at high altitudes, the dilatation of the Jimb-vessels must be counterbalanced by vaso-constriction else- where, presumably in the splanchnic area. There is at present no evidence to show which of these is the primary process. Schneider and Sisco regard the increased frequency of the pulse as an adaptive change in response to oxygen-want, since they found that the inhalation of Oxygen slowed the pulse. But a similar decrease in pulse-rate has been observed to take place as a result of inhalation of oxygen at low levels, although, in these circumstances, oxygen-want did not previously exist. There is at present no satisfactory explanation of the greater frequency of the pulse in the resting individual at high altitudes, and it is not easy to understand how the acceleration at high altitudes can be in any way advantageous to the circulation. The Passage of Oxygen into the Blood. It has been found both by Douglas, Haldane, Henderson, and Schneider and by Hasselbalch and Lindhard that, in the resting individual, the consumption of oxygen at high altitudes is the same as at ordinary levels. TABLE XXXVIII. — Oxygen-Consumption in c.c. per Minute. Barometric Pres- sure 750-760 mm. Hg. Barometric Pres- ure 450 mm. Hg. Douglas, Haldane, Henderson, and Schneider . Hasselbalch and Lindhard .... 237 330 2ig 248 345 220 Durig and Zuntz observed a greater consumption of oxygen at high altitudes than at low levels. It is probable, however, that the individuals in whom this occurred were not fully acclima- tised, since Hasselbalch and Lindhard have also found that the consumption of oxygen is increased during the transitional stage before adaptation has become complete. Since the minute-volume of the heart is also unaltered, it is i6o THE PHYSIOLOGY OF MUSCULAR EXERCISE clear that, in the resting individual at a high altitude, the blood must take up its normal amount of oxygen from the lungs, and that, unless it undergoes much greater reduction than usual during its passage through the tissues, the blood must leave the lungs almost as fully saturated with oxygen as at low levels. Opinion is sharply divided, however, as to the means by which the passage of oxygen into the blood at high altitudes is effected. Krogh holds that oxygen enters the blood, both at low levels and at high altitudes, solely by diffusion through the pulmon- ary epithelium, whereas Douglas and Haldane, while accepting diffusion as the only process concerned in the resting man at low levels, consider that, at high altitudes, diffusion will not account for the intake of oxygen, and that this is brought about by active secretion on the part of the pulmonary epithelium. The Diffusion Theory. On the diffusion hypothesis, the amount of oxygen entering the blood per minute is the product of the diffusion-coefficient of oxygen through the membrane separating the alveolar air from the blood and of the mean difference between the tension of oxygen in the alveolar air and in the blood flowing through the pulmonary capillaries. The diffusion-coefficient is defined as the amount of oxygen in c.c. which can diffuse through the alveolar membrane in one minute, when the difference of oxygen- pressure on the two sides of the membrane is i mm. In 191 1, A. and M. Krogh found that the diffusion-coefficient might.be 25. More recently (1915), M. Krogh has shown that the coefficient varies from 23 to 43 in different individuals during rest, and that, when the surface area of the lungs is increased by greater pulmonary expansion, for example, during exercise, it ranges from 37 to $6. In the determination of the coefficient, the assumption is made that the alveolar membrane is watery ; and some observations of Cushny on the exhalation of volatile substances through the lungs favour this view. But it is not certain that such is the case. Lipoids exist in almost all membranes in the body, and as Bayliss has pointed out, the presence of lipoid in the alveolar membrane would greatly increase the diffusion coefficient. The values of the coefficient, as determined by M- Krogh, must, therefore, be minimal values. On Pike's Peak, Douglas absorbed during rest 345 c.c. oxygen per minute. Taking an average value for the diffusion- THE PASSAGE OF OXYGEN INTO THE BLOOD i6i coefficient, namely 33, this amount of oxygen could enter the blood by diffusion, if the difference between the tension of oxygen 345 in the alveoli and that in the blood were — -- = lO'? mm. As- 33 suming the blood leaving the lungs to be in equilibrium with the alveolar tension of oxygen, it would be 85 per cent, saturated ; and, if the blood lost 32 per cent of its oxygen in passing round the body, the venous blood would be 53 per cent, saturated, this representing an oxygen-tension of 32 mm. Hg. If the blood, instead of coming into equilibrium with the alveolar air, becomes only 80 per cent, saturated in the lungs, the oxygen-tension of the venous blood would be 28 mm. Hg. The maximum tension-difference then is 22 or 26 mm. Hg. The tension- difference falls, however, as the blood travels along the capil- laries, and the mean tension-difference, when roughly integrated by the method described by Bohr, is about 12 or 13 mm. Hg ; this is more than sufficient to provide for the absorption of 345 c.c. of oxygen by diffusion alone. The relationship between the oxygen-consumption of an individual and his diffusion-coefficient has not been worked out, but, since the former corresponds roughly with the muscular de- velopment of the individual, it is not improbable that a large oxygen-absorption is associated with increased alveolar surface and, consequently, with a large diffusion-coefficient. Assuming that the oxygen-absorption and the diffusion-coefficient are re- lated in this way, the evidence for the diffusion theory is more convincing than that indicated by the foregoing example, since an oxygen-absorption of 345 c.c. per minute is rather large for a resting man, and it seems quite possible that Douglas' diffu- sion-coefficient might be 40 or thereabouts. In this case, a mean difference of 8 '5 mm. Hg between the tension of oxygen in the alveolar air and in the capillary blood in the lungs re- spectively would provide for the required absorption of oxygen. Moreover, the increased pulmonary ventilation at high altitudes would tend to raise the diffusion-coefficient still further, and, in these circumstances, a still smaller mean difference of tension would be adequate. The assumption that the venous blood loses one-third of its oxygen in passing through the tissues is, however, not always correct. Taking the consumption of oxygen per minute to be II 1 62 THE PHYSIOLOGY OF MUSCULAR EXERCISE 240 c.c, the output of the heart to be 4 litres per minute, and the oxygen-capacity of the blood, when 96 per cent saturated, to be 181 c.c. per litre, the blood would lose one-third of its oxygen if each litre gave off 60 c.c. to the tissues. If, at high altitudes, the blood left the lungs 80 per cent, saturated, and the haemo- globin percentage ' rose to 118, the oxygen-carrying power of the blood would be almost unchanged, and the percentage satura- tion of the venous blood would be 5 3 per cent. But if, as might well occur, the haemoglobin percentage rose to 1 34 the oxygen- carrying power of the blood would be 201 c.c. per litre ; the removal in the tissues of the usual 60 c.c. of oxygen would then leave the venous blood 56 per cent, saturated, and its oxygen- tension would be 33 mm. Consequently, the difference between the tension of oxygen in the alveoli and in the venous blood reaching the lungs would be lessened. Hence, any excess of haemoglobin (per unit volume of blood) beyond that required to compensate for the diminished saturation of the blood at high altitudes has the effect of raising the venous oxygen-pressure, and thereby reducing the mean difference of oxygen-tension upon which the diffusion of oxygen depends. This could, of course, be met by a slight fall in the saturation of the arterial blood, and, consequently, of the venous blood, which, while not affecting the absorption of oxygen, would tend to pro- duce, or to accentuate, cyanosis. Douglas, Haldane, Henderson, and Schneider state indeed that blood which is 85 per cent, saturated with oxygen is distinctly darker in colour than that saturated to 95 per cent., and they consider that the absence of any sign of blueness of the mucous membranes in acclimatised individuals is a strong argument against the diffusion theory. The direct comparison of two samples of blood, examined side by side in vitro, is, however, a much more delicate method of observation than inspection of a mucous membrane. Further, owing to its greater content of haemogoblin, the saturation of the blood in the capillaries of the mucous membranes probably differs less from that of arterial blood at high altitudes than at low levels. It is not certain, therefore, that, when the arterial blood is only 85, or even 80, per cent, saturated, this will produce any recognisable change of tint in the mucous membranes, and the absence of cyanosis in acclimatised men on Pike's Peak is not inconsisteipt with the diffusion theory. Moreover, even though THE PASSAGE OF OXYGEN INTO THE BLOOD 163 the venous oxygen-pressure is raised by an excess of haemoglobin, the mean difference of oxygen-tension is probably sufficient to allow the blood, as it flows through the lungs, to become satu- rated almost to the alveolar oxygen-tension, unless the diffusion constant in any individual is unusually small relatively to the absorption of oxygen. The explorations of the Due d'Abruzzi and his companions in the Himalayas probably provide the most severe test to which the diffusion hypothesis has been subjected. The barometric pressure was 312 mm. Hg, and the oxygen-pressure of the alveolar air is calculated by Haldane and his colleagues as being about 30 mm. Hg. They point out that blood, when in equi- librium with alveolar air at this pressure, is not quite half satur- ated with oxygen, the percentage of saturation corresponding with that found in the arterial blood of animals just before death from asphyxia, and that, on the diffusion theory, the saturation of the blood would be even less. Since the explorers felt no discom- fort during rest and were even able to take a moderate amount of exercise, Haldane and his colleagues conclude that the diffusion hypothesis breaks down. This figure for the alveolar tension of oxygen is not accepted by M. Krogh. On the basis of Haldane's assumption that the members of the expedition were doing work involving an oxygen- consumption of 1,000 c.c. per minute, and assuming further that the ventilation per minute measured 1 1 1 -3 litres, M. Krogh finds that the alveolar oxygenrtension would be 47 mm. Taking the diffusion-coefficient as 56, the absorption of 1,000 c.c. of oxygen could be obtained with a mean tension difference of 17 '8 mm., which would be possible if the arterial blood were 60 per cent, saturated. M. Krogh concludes, therefore, that the results of the D'Abruzzi expedition are not incompatible with the diffusion theory, although marked cyanosis must have been present. It appears then that, even at high altitudes (up to 24,000 feet), the passage into the blood of sufficient oxygen to enable a man not merely to exist, but to live with comparatively little discom- fort, and even to take exercise, when once he has become ac- climatised, can be effected by diffusion alone, and that, at least on Pike's Peak, the diffusion hypothesis not only avoids being wrecked on the Scylla of secretion, but also, in the resting indi- vidual, evades the Charybdis of cyanosis. 1 64 THE PHYSIOLOGY OF MUSCULAR EXERCISE The Secretion Hypothesis. This conclusion deprives the secretion hypothesis of one of the two main arguments advanced in its support, namely, the inadequacy of the diffusion theory to account for the facts. But there remains the direct evidence brought forward by Douglas, Haldane, Henderson, and Schneider that, on Pike's Peak, the tension of oxygen in the arterial blood is considerably higher than that in the alveolar air. Employing the carbon monoxide colorimetric method, they found that the average pressure of oxygen in the arterial blood was 88 '3 mm. Hg, and, since the average alveolar pressure of oxygen was 52-5 mm. Hg, the tension of oxygen in the arterial blood was 3 5 "8 mm. Hg higher than that in the alveolar air. In one subject, who had just ascended the Peak, and who was cyanosed, the pressure of oxygen in the arterial blood exceeded that in the alveolar air only by a few millimetres. On the ground of these observations, Haldane and his col- leagues hold that increased secretory activity of the pulmonary epithelium, by raising the tension of oxygen in the arterial blood, makes acclimatisation possible, and that the development of secretory activity is a gradual process. At an oxygen-tension of 88 mm. Hg, the blood will be 95 per cent, saturated ; in that case, the process of compensation for the high altitude is so com- plete that there is no obvious reason why, on Pike's Peak, the individual should differ in any respect (apart from the activity of his pulmonary epithelium) from a man at sea-level. What, then, is the explanation of the progressive increase in the percentage of haemoglobin in the blood, an increase which continues even after the secretory activity of the pulmonary epithelium has had time to develop? Haldane and his colleagues believe that, at low barometric pressures, easily oxidisable metabolites pass through the lungs into the arterial blood in abnormally high proportions, that these substances are oxidised in the blood on its way through the body, and that the rise in the percentage of haemoglobin, by increasing the oxygen-content of the arterial blood above the normal level, permits this oxidation to take place without any reduction in the supply of oxygen to the tissues. It is difficult to understand, however, how, if the saturation THE CHANGES DURING EXERCISE 165 of the blood is normal and its oxygen-carrying power greater than normal, the metabolism of the subject can be affected, and how the oxidation processes in the tissues can be less efficient than usual. Nor does it seem possible (on the secretory view) to account for the change in the reaction of the blood, which Haldane and his colleagues regard as being responsible for the increased pulmonary ventilation, although this doubtless renders easier the task of the pulmonary epithelium. Even if the pulmonary ven- tilation were unaltered and the alveolar oxygen-tension remained at 38 mm., an excess of 3 5 "8 mm. in the tension of oxygen in arterial blood over that in alveolar air would enable its haemo- globin to become 92 per cent, saturated with oxygen, a value quite sufficient at low levels. Further, the occurrence of periodic (Cheyne-Stokes) breath- ing in the acclimatised man, sometimes only on slight exertion, but in some individuals even during sleep, does not accord with the view that the blood is normally saturated with oxygen, since Douglas and Haldane (1909), have clearly shown that it is usually caused by lack of oxygen, and Pembrey and Allen (1905) found that it was abolished by inhalation of oxygen. Apart from these objections to the views of Haldane and his co-workers, Hartridge's (1912) evidence appears to throw some doubt on the validity of the colorimetric method employed by Haldane. Hartridge's observations indicate that, when the air breathed contains a diminished percentage of oxygen, the tension of oxygen in the arterial blood is not higher than that of the alveolar air. But these experiments are hardly relevant, since the lack of oxygen was very temporary, where- as Douglas, Haldane, Henderson, and Schneider hold that prolonged lack of oxygen is necessary to develop the secretory activity of the pulmonary epithelium. Bayliss (1915) has suggested that possibly the greater percentage of haemoglobin in the blood may interfere with the accuracy of the carbon monoxide method. To quote a remark made by Gibbon in another connection, " it is not the duty of the (writer) to interpose his private judgment in this nice and important controversy," which will, perhaps, be finally settled only by direct determination of the oxygen-tension and percentage saturation of the arterial blood of a completely acclimatised individual at a high altitude. In the meantime, however, M. Krogh's evidence appears to have weighted the scales heavily in favour of the diffusion theory. The Changes During Exercise. Rapid walking on Pike's Peak may increase the oxygen con- sumption to 2,000 c.c. per minute, and, during a short run, this 1 66 THE PHYSIOLOGY OF MUSCULAR EXERCISE figure may doubtless be exceeded, though only for a few moments. Such a rise in the consumption of oxygen can take place only if the mean difference between the tension of oxygen in the alveolar air and that in the blood reaching the lungs is greatly increased ; this is effected partly by a rise in the tension of oxygen in alveolar air, and partly by greater reduction of the blood during its transit round the body. At low levels, the increased pulmon- ary ventilation during exercise leaves the alveolar oxygen-tension 120 ; no c 100 i c 90 V ■j 70 o 60 *i3 C9 = 50 c > 40 « c o 0. 30 20 10 % / / / i / X ^ y y^ ..---' .-^■' y y -''' ..-•■ 5 / < ."• ^'^0 ^y y c o'' x^ ^.. ^' y ■Jr^ 200 400 600 600 1000 1200 1400 1600 1800 2000 2200 2400 2600 Oxygen Consumption in c.c. per Minute. Fig. 21. — (Constructed from Douglas, Haldane, Henderson, and Schneider's data.) Upper curve = ventilation on Pike's Peak. Lower curve = ventilation at Oxford. almost unaltered, whereas, on Pike's Peak, the pulmonary ventila- tion during exercise is exaggerated to such an extent (Fig. 21) that the alveolar tension of carbonic acid falls and the tension of oxygen may increase to 68 or 6g mm. At the same time the coeiificient of utilisation rises consider- ably, the result being that the tension of oxygen in the venous blood falls and the mean difference of tension between the alveolar air and the venous blood may reach 38 to 40 mm. Taking the diffusion-coefficient during muscular work to be just THE CHANGES DURING EXERCISE 167 over 50, this difference of tension will allow of the passage into the blood of roughly 2,000 c.c. of oxygen per minute, which is almost the highest figure recorded by Haldane and his co- workers. The hyperpncea or dyspnoea induced by exercise at high altitudes is, therefore, necessarily greater than at low levels ; it is due, partly to heightened excitability of the respiratory centre, and partly to the greater rise in the C„ of the blood during exercise under these conditions. The actual effect of exercise on the passage of oxygen into the blood, however, is not so simple as these figures seem to indicate, since the circulation rate through the lungs also be- comes greater during exercise. In consequence of the smaller difference between the pressure of oxygen in the alveolar air and that in the venous blood at high altitudes, the rate of diffusion must be slower than at low levels. Consequently, as the flow of blood through the lungs becomes more rapid, less and less time is available for the passage of oxygen into the blood, and the percentage saturation with oxygen of the haemoglobin in the blood leaving the lungs inevitably falls. The fall in the tension of oxygen in the arterial blood brings about two effects. In the first place, it tends to lessen the amount of oxygen carried from the lungs to the tissues. In the second place, it slows down the rate at which the blood gives up its oxygen to the tissues. It is from this point "of view that the haemoglobin content of the blood, and its rate of dissociation, become of such importance for the maintenance of an adequate difference of tension between the alveolar air and the blood. Barcroft and his associates (191 5) have shown that a given amount of exercise increases the H • ion concentration of the blood to a greater extent at high altitudes than at low levels ; and, in all probability, the local con- centration of acids in the capillaries of the active muscles is also greater under these conditions. The dissociation of oxyhaemo- globin, as the blood flows through the active tissues, is thereby accelerated, and the venous blood is more fully reduced. The fall in the oxygen-tension of the venous blood favours the more rapid diffusion of oxygen into the blood in the lungs, although this will be accompanied by cyanosis. Again, the higher the percentage of haemoglobin in the blood, i68 THE PHYSIOLOGY OF MUSCULAR EXERCISE the slower is the qirculation rate necessary for the transport of a given amount of oxygen from the lungs to the tissues, and hence the higher will be the pressure of oxygen in the arterial blood. The hsemoglobin content of a man's blood is, therefore, of vital importance in determining the intensity of the exercise which he can perform at a high altitude, and, from this point of view, the haemoglobin value of his blood is probably the truest index of the extent to which a man is acclimatised i to high altitudes. It might be anticipated that, owing to the greater haemo- globin content of the blood, the circulation rate would increase less rapidly at high altitudes than at low levels. On the other hand, the higher arterial pressure and greater concentration of acid metabolites in the muscles will presumably cause a more rapid flow of blood through the muscles than at low levels, and the mechanical pumping action of the muscles will bring about a correspondingly larger venous inflow to the heart, which will tend to increase its output and hence the circulation rate. The available data do not permit of any conclusion as to whether, for a given amount of exercise, the circulation rate at high altitudes diff'ers from that at low levels. Nor is there at present any evidence that failure on the part of the circulatory system is responsible for the lessened ability of the individual to perform exercise at high altitudes. It is clear, then, that since, on the one hand, a more rapid circulation rate is required to carry oxygen from the lungs to the tissues, and, on the other hand, such an increase in rate gradually lowers the tension of oxygen in the arterial blood, the limit of exercise at high altitudes is reached when the tension of oxygen in the arterial blood becomes inadequate for the needs of the tissues. In other words, the amount of oxygen passing into the blood sets the limit to the amount of exercise which a man can perform at "high altitudes, whereas, at low levels, the decisive factor is the rate at which oxygen can be carried from the lungs to the tissues. The first tissue to suffer visibly from the lowered tension of oxygen in the arterial blood is the central nervous system. It is for this reason that, even in the acclimatised subject, severe exercise brings on the characteristic symptoms of "mountain sickness ". It is probable, indeed, that many climbing accidents SUMMARY 169 are caused, not by failure of the muscles but by a sudiden aberra- tion of judgment or disturbance of co-ordination induced by an insufficient supply of oxygen to the brain. Short of manifest signs of lack of oxygen, such as giddiness or faintness, the exaggerated respiratory movements and the high arterial pres- sure, may be looked upon as directly or indirectly the result of increased sensitiveness of the central nervous system to lack of oxygen. The effect may depend upon greater H- ion concentra- tion of the blood reaching the brain, or may be secondary to the production of acid within the brain itself It is possible, too, that a larger discharge of adrenalin into the blood-stream may be in some measure responsible for the excessive circulatory re- sponse to exercise, since a comparatively slight anoxaemia evokes a greater outflow of adrenalin into the circulation (Kellaway). Although a man, when taking active exercise at a high alti- tude, must almost invariably be hampered to some extent by lack of oxygen, the deficiency of oxygen may be almost imper- ceptible, so long as the pulmonary ventilation continues to in- crease. But the margin of safety during exercise is so slight that the adapting mechanisms, which maintain the supply of oxygen, soon reach the limit of their effectiveness, and even a trained and acclimatised man cannot perform as vigorous exercise as at low levels. None the less a trained man is better equipped than an untrained man, assuming both men to be acclimatised, partly because, in all probability, his diffusion coefficient for oxygen is larger, and partly no doubt owing to the better co-ordination of his muscles during exercise. The greater range of pulmonary ventilation, which seems to exist in the trained subject, must also add to his capacity for exercise by making possible a larger alveolar tension of oxygen, and consequently more rapid diffusion of oxygen into the blood. There is also some evidence that the haemoglobin value of the blood is normally higher in the trained, than in the untrained, man. This confers a still further advantage on the trained man at a high altitude since, even be- fore acclimatisation has taken place, he will be less liable than an untrained man to suffer from " mountain sickness ". Summary. The characteristic features of exercise at high altitudes are, first, that the circulatory and respiratory changes produced by a given I70 THE PHYSIOLOGY OF MUSCULAR EXERCISE amount of exercise are greater than at low levels, and, second, that the maximum amount of work which a man can perform is less than at low levels. These features are present even in the ac- climatised individual, and are very conspicuous in a man suffering from " mountain sickness ". Even in the acclimatised subject, the pulmonary ventilation is approximately 50 per cent, greater (and the alveolar tension of carbonic acid is lower) than at low levels, although the re- action of the blood scarcely differs from that at, or near, sea-level. The question whether the greater pulmonary ventilation is brought about primarily by a rise in the C„ of the blood, or by greater excitability of the respiratory centre to a normal chemical stimulus, is discussed. The greater pulmonary ventilation raises the alveolar tension of oxygen from 35-8 mm. Hg to 52 to 55 mm. Hg (the baro- metric pressure being 457 mm. Hg), thereby rendering it possible for the blood leaving the lungs to be 85 per cent, saturated with oxygen instead of only 65 per cent, saturated. After acclimatisation to high altitudes, the output of the heart and the arterial blood pressure are the same as at low levels, whereas the pulse is more frequent and the venous pressure is less than at low levels. At a high altitude, a resting acclimatised man consumes as much oxygen per minute as at low levels. The question whether, not only in the resting man, but also during exercise, the passage of oxygen from the lungs into the blood is effected solely by diffusion, or whether it involves secretory activity on the part of the pulmonary epithelium, is discussed. During exercise at high altitudes the pulmonary ventilation is exaggerated to such an extent that the tension of oxygen in the alveolar air rises considerably (10 to 15 mm.), thereby allow- ing oxygen to diffuse more rapidly into the blood. At the same time, the more rapid flow of blood through the lungs tends to lower the saturation with oxygen, and the oxygen-tension, of the blood leaving the lungs. The limit of exercise is ireached when the percentage saturation of the arterial blood with oxygen falls to such a level that the tissues can no longer take up sufficient oxygen for their requirements and suffer from lack of oxygen. CHAPTER XL THE AFTER-EFFECTS OF EXERCISE— CIRCULATORY AND RESPIRA- TORY CHANGES — FATIGUE — THE BENEFICIAL EFFECTS OF EXERCISE. Circulatory and Respiratory Changes. Most of the circulatory and respiratory changes associated with the carrying out of exercise pass off remarkably quickly after the conclusion of exercise, and, at least as regards the output of the heart, the circulation rate, and the blood-pressure, the transition to the resting state may often be completed, even after severe and prolonged exertion, within a quarter of an hour. Immediately on the cessation of exercise, the skeletal muscles send back the blood to the heart less rapidly, and its diastolic volume and out- put per minute begin to diminish within a few seconds. At the same time there is a sudden relaxation of nervous tension and of muscular tone, and the man stands or sits passive with slack muscles. Further, partly owing to the stoppage of the muscular pump, partly in consequence of lessened activity of the medullary centres, the arterial pressure falls rapidly, and, after a short bout of exercise, it may reach its normal resting level within three or four minutes (Cotton, Rapport, and Lewis). Even after pro- longed and severe exertion, the arterial pressure soon falls to, or, for a short time, below, its normal level. The frequency of the pulse also decreases very rapidly after exercise, and, according to the observations of Cotton, Rapport, and Lewis, it may return to its resting rate within five minutes after the conclusion of a brief period of exercise (Table XXXIX.). It is clear, however, from some of Pembrey's (1909) observa- tions that, after more prolonged exercise, such as running half a mile or more, the pulse-rate may remain above its normal level for an hour, or even longer, after the conclusion of the exercise. In one of Pembrey's experiments the pulse-rate during rest was 68. Immediately after a run of one mile the subject had a pulse-rate of 164, and an hour later it was 82. 171 172 THE PHYSIOLOGY OF MUSCULAR EXERCISE K o o T X I-] m < m Ilii i 2 -2 •« S ills CQ '^ ^^ * 1 • •S "a m" S §111 = Wco COM 1^ « O U z« 000 000 ° p rr% 01 C4 10 t^ H H M N « H N M H l-l •i li u lA »« ? ■i3 X >. M (O H » « a^oo (1. S "(J- « « -i- « M M & g % S ,« • 5? K n « inr^oo 0» 01 fN-* *o rh m « to m ro m >• IS 2 H H H H H H H H . N H M m fO fO N P. H H H H M M M M V H> o'^ 00 « Tf- m in tnoo 'SS t^ t^C^^XJp 00 00 ai at a if as 000 000 00 VO TfN « 00 10 ■«■ M 303 ■t o s 000 000 o oi ■^ CO « M VD >!|- CO N o «£:; ^ ^S ^. ^ , H « «« i*j u U u V :o' 'S 9 ■a CO CO THE AFTER-EFFECTS OF EXERCISE 173 Martin, Gruber, and Lanman (191 4) also found that, al- though the pulse-rate rapidly decreased after exercise, it did not return to normal for more than an hour. Their observations were made both on a trained and on an untrained individual, and the exercise consisted in running up and down stairs for three to six minutes. Similar results were obtained by Benedict and Cathcart (191 3). In Benedict and Cathcart's experiments, the 190 180 170 160 150 140 130 120 110 100 90 80 70 60 80 10 20 SO 40 50 60 70 80 90 100 110 120 130 140 150 160 170 Fib. 22. — (From Benedict and Cathcart.) Figures along abscissa = time in minutes. Figures along ordinate = pulse-rate per minute. Arrows indicate the beginning and end of the exercise. y ^ y 1 ^r0^ / \ \ / ; \ '/ : / \ / . .. ^^ \ / / N // ^ V,. \ // ^^ Ci: ::::; 1^ i^ \C \ f \f. - f f — exercise was severe and rather prolonged ; exercise the pulse-rate fell rapidly at first, sometimes for several hours, at a distinctly fore the exercise (Fig. 22). The prolonged slight acceleration of the is not associated with raised temperature Martin, Gruber, and Lanman found that the rate and the fall in the temperature of the did not necessarily correspond as regards at the end of the and then remained, higher rate than be- pulse after exercise of the body, since decline in the pulse- body after exercise their time-relations. 174 THE PHYSIOLOGY OF MUSCULAR EXERCISE Benedict and Cathcart believe that the higher pulse-rate after exercise is correlated with the increased metabolism which is one of the after-effects of exercise, and to which attention was first called by Speck (1892). Benedict and Cathcart showed that the total metabolism of the individual, when measured either by the consumption of oxygen or by his production of heat, might remain distinctly above his ordinary resting level for as long as two to four hours after exercise (Table XL.). Whatever may be its significance, the correspondence between the heightened metabol- ism and the greater frequency of the pulse after exercise furnishes an additional instance of the close relationship, existing under almost all conditions, between the pulse-rate and the consumption of oxygen by the body. The character of the metabolic changes is not known, though presumably the oxidation of lactic acid, both in the muscles themselves and in other tissues into which it has diffused during exercise, must be one of these changes. An interesting and curious fact, noted by Benedict and Cathcart, is that the increased consumption of oxygen is not accompanied by a larger pulmonary ventilation. TABLE XL. — (Benedict and Cathcart.) Metabolism of Subject Lying on a Couch Before and After Work. Resting before work Oxygen Ab- sorbed: c.c. per Minute. Heat Output per Minute in Calories. 233 Duration of Work — One Hour, I-I5 Pulse-rate. 62 5 minutes after end of exercise 54 i» '» »» '» »* 7° »» »> »» »» »» 102 ,, ,, ,, ,, ,, 407 311 306 293 1-93 100 1-46 88 1-44 85 1-38 83 The period required for the pulmonary ventilation to return to its normal level after exercise depends almost entirely upon the reaction of the blood at the conclusion of exercise. If little or no lactic acid has been added to the blood, the excess of carbonic acid in the blood is very quickly removed by the lungs. If, however, lactic acid is present in the blood in considerable amount, the hyperpncea continues until, by the washing out of THE AFTER-EFFECTS OF EXERCISE 175 carbonic acid, the alveolar tension of carbonic acid falls sufB- ciently to bring the reaction of the arterial blood to its resting H CO? value. At this point the ratio tjtsj p/-), is normal, although both the tension of carbonic acid in the blood and the bicarbonate of the plasma are reduced. This condition, which Hasselbalch terms " compensated acidosis," gradually passes off, and the alkali-reserve of the plasma and the tension of carbonic acid regain their normal level. The restoration of the alkali-reserve is effected partly by the excretion of lactic acid and of acid phosphate by the kidneys, thereby setting ' free base which can form bicarbonate, and partly, no doubt, by interchange of acid and basic radicles between the plasma and the tissues. After a brief period of moderate exer- cise, the restoration of the alkali- reserve and the alveolar tension of carbonic acid to their normal resting level takes place fairly rapidly as the following figures show : — TABLE XLI. — (From Douglas and Haldane.) Alveolar Tension of CO2 in mm. Hg. Rest Just after running 300 yards 10 minutes later 15 25 43 60 38-2 45-7 35-6 33-0 33-8 37-8 38-4 Mettenleiter (191 5) states that, after prolonged and severe exertion, a slight compensated acidosis, as indicated by a lowered alveolar tension of carbonic acid, may persist for twenty-four hours or even longer. The temperature of the body falls rapidly after the conclusion of exercise (Fig. i). Bardswell and Chapman (191 1) made the interesting observation that it almost invariably falls to normal within an hour after exercise, however high it may rise during the course of the exercise. A subnormal temperature for a short time has also been noticed after exercise (Pembrey, 1909). The time taken for the temperature of the body to fall to its rest- ing level, however, naturally varies to some extent with the 176 THE PHYSIOLOGY OF MUSCULAR EXERCISE conditions under which the individual is placed, and, what is even more important, with his general health. Fatigue. The changes just described represent the gradual subsidence of the processes invariably associated with the carrying out of muscular work, whereas fatigue is not a necessary result of exercise and appears only when this is severe or prolonged. Fatigue, as it occurs in man, presents two aspects, the one ob- jective and the other subjective. Its outward manifestation is a diminished capacity for doing effective work ; its chief subjective symptoms are defined by MacDougall (1908), as (i) a feeling of local tiredness in the active muscles ; (2) a general sensation of tiredness ; and (3) sleepiness. The causation of the sensation of fatigue is rather obscure. Joteyko (1904) has suggested that the local feeling of fatigue is the result of impulses set up in sensory structures, such as the muscle spindles, which subserve muscle sense, and that these endings are stimulated by the chemical products of muscular activity. Frumerie (191 3) points out that the sense of fatigue is referred at first to the joints and tendons, in which there is no accumulation of these products, and he suggests that it is more likely to be due to prolonged mechanical stimulation of nerve- endings in joints and tendons. If this view is correct, the local sense of fatigue is in no way related to the actual processes taking place within the muscle itself. One difficulty in accept- ing this suggestion is that, after the same amount of exercise and, presumably, approximately the same degree of mechanical stimulation of nerve-endings, an untrained man may feel fatigued, whereas a trained man is not tired. Possibly, however, the mechanical stimulation of nerve-endings is really greater in the untrained than the trained man, since the latter utilises his muscles more efficiently. Whatever its origin may be, the sense of fatigue is often a very fallacious index of the working capacity of the body. Johansson (1902) and, more recently, Frumerie have found that, when a single group of muscles is examined, there is not necessarily any correspondence between the subjective feeling of fatigue, and the capacity of the muscles to perform work. A man is not always as tired as he feels, and an almost normal FATIGUE 177 capacity for work may coexist with marked subjective fatigue (Myers, 1918). On the contrary, in certain circumstances, the sensation of fatigue may be slight or absent, although the output of work is falling off. None the less, it is probably true that a subjective feeling of fatigue, does, as a rule, indicate a lessened capacity for work, and that, as Pembrey (1909) has suggested, it is a protective feeling, which tends to restrain a man from continuing to perform muscular work when this would react injuriously upon his whole system. , This sensation may be temporarily annulled by strong emotion, and, simultaneously, the amount of work which a man can perform may be increased. But, when a man, who is already tired, is spurred on by emotion to fresh effort, the subsequent fatigue, both subjective and ob- jective, is often extreme and out of all proportion to the exer- tions made. The only trustworthy measure of fatigue, however, is the diminution in a man's capacity of performing work, and it has long been recognised that, in daily life, the main seat of fatigue after muscular exercise is the central nervous system. Even in ergographic experiments, Mosso long ago stated that "nerv- ous fatigue is the preponderating phenomenon, and muscular fatigue also is at bottom an exhaustion of the nervous system ". There appear, however, to be two types of fatigue, one arising entirely within the central nervous system, the other in which fatigue of the muscles themselves is superadded to that of the nervous system. Every resting muscle possesses a store of potential energy, and the setting free of its energy is intimately bound up with the liberation of lactic acid ; hence the possible sources of fatigue of a muscle are, on the one hand, exhaustion of its store of energy, and, on the other hand, clogging of the muscular machine by its metabolic products. Up to a certain point, greater concentration of lactic acid, or strictly speaking H" ions, on the surface of the colloidal system of muscle fibrils increases the tension change and the setting free of energy within the muscle (Mines, 191 3). Beyond this point, the accumulation of acid prevents the com- plete restoration of the fibrils to their resting condition after each contraction, and the discharge of energy at each successive con- traction diminishes. The restoration of a muscle's store of energy depends upon 12 178 THE PHYSIOLOGY OF MUSCULAR EXERCISE either the oxidation of lactic acid within the fibres (Hopkins and Fletcher), or upon the replacement of this acid in some un- stable chemical complex (A. V. Hill). Consequently, the ac- cumulation of lactic acid within the muscle, not only hampers the discharge of energy at each contraction, but implies that its store of energy is diminishing. In order that the muscle may remove lactic acid almost as rapidly as it is formed, and may renew its potential energy by utilising the crude energy presented to it as fat or carbohydrate, an adequate supply of oxygen is essential. Although this is normally ^provided during exercise, it is probable, as has been pointed out (p. 39), that, during severe prolonged exertion, the supply of oxygen is sometimes inadequate ; in these circum- stances, lactic acid is produced much more rapidly than it can be removed by oxidation or otherwise, and the muscles them- selves become fatigued. Fatigue, induced in this way, may occur during a boat-race or in long-distance running, for example, a Marathon race, although even here fatigue of the nervous system must play an important and perhaps predominant part, since, under these conditions, the brain is apt to suffer quite as much as the muscles from lack of oxygen. Another factor, which may contribute to the production of this type of fatigue, is fatigue of the heart itself. Although the occurrence of fatigue of the heart in health is not very clearly established, a temporary lowering of the functional capacity of the heart, induced by fatigue of its muscular fibres, might gradually bring about during exercise an insufficient blood-supply to the skeletal muscles and the brain. The lassitude and disinclination for exertion, often experienced on the day after a strenuous bout of exercise, has also been ascribed to fatigue of the heart as its primary cause. The type of fatigue in which the muscles, as well as the nervous system, are involved is not the most common type, since, at least in a man accustomed to physical exertion, it demands an intensity and persistence of muscular eiifort, which is not usually called for under the ordinary conditions of life among manual workers. In many forms of manual work, there is no evidence, either that the production of lactic acid in the muscles appreciably outruns its destruction, or that the heart fails to meet the needs of the muscular and nervous systems for oxygen ; and, in the FATIGUE 179 more strenuous kinds of industrial work, the accumulation of waste-products within the muscles is usually delayed or prevented by the interposition of brief rest periods at frequent intervals. The possibility that, in these workers, a gradual accumulation of waste products in the muscles may occur as the day goes on, and that this may ultimately clog the activity of the muscles, appears to be negatived by the rapidity with which the muscles get rid of these products and with which purely muscular fatigue can disappear. And it seems unlikely that as a rule changes in the muscles themselves take any real share in the production of in- dustrial fatigue. There is, indeed, good reason to believe that, broadly speaking, fatigue, as it occurs among industrial workers, has its origin entirely within the central nervous system (Report of Health of Munition Workers' Committee, 191 8), although this conclusion does not exclude the possibility that occasionally, for example, under abnormally severe stress of very heavy work, fatigue of the muscles themselves may also supervene. Admitting, however, that, as a rule, fatigue after muscular work is essentially a nervous phenomenon, the view has been ad- vanced (McDougall, McKenzie, Hedvall), that metabolic products of muscular activity are responsible, at least in part, for bringing about fatigue of the central nervous system. These products are of two kinds, namely, lactic and carbonic acids and metabolites other than acids. Neither lactic nor carbonic acid ever attains during exercise such a concentration in the blood as to be directly toxic, and the only possible way in which, so far as is known, they can influence the nervous System is by altering the reaction of the blood. The rise in the H' ion concentration of the blood during ordinary physical work is so slight that it is difficult to believe that it produces any harmful effect upon the central nervous system, the more so since a trivial rise in H' ion concentration is stimulating rather than depressing. It is conceivable that, during intense exertion, the reaction of the blood might alter sufficiently to disturb the nervous system as a whole. There is no positive evidence, however, in support of this view, and the efficiency of the mechanisms which regulate the reaction of the blood is so great that such an occur- rence seems improbable. There is some evidence (p. 94) that metabolites, other than IS* i8o THE PHYSIOLOGY OF MUSCULAR EXERCISE acids, are, or may be, formed during muscular activity, and may enter the blood-stream. The evidence of their existence is almost confined, however, to the fact that a neutral extract of muscle may bring about loss of tone of arterioles and possibly of capil- laries, when injected into an animal (Vincent and Sheen, Bayliss). Nothing is known as to their chemical nature, nor is there any reason to believe that they have any action upon the central nervous system. There appears, therefore, to be at present no secure founda- tion for the belief that the products of muscular activity take any share in bringing about fatigue of the nervous system, either directly or by altering the reaction of the blood. Such evidence as is available points rather to failure of the heart as underlying the comparatively rare cases of extreme nervous collapse described as occurring during intense exertion. Short of actual collapse, the frequent occurrence of giddiness, faintness, or nausea, indicate some degree of cerebral anaemia, and it is not improbable that a still slighter shortage in the supply of oxygen to the brain may accelerate or even induce fatigue. It is doubtful, however, whether this factor contributes to the production of fatigue under ordinary industrial conditions, and the origin of fatigue, either after exercise or among industrial workers, must be sought in changes tajcing place entirely within the nervous system, and arising as the outcome of the activity of the nervous system. The real nature of these changes is still almost unknown, but, during prolonged exercise, the steady out- flow of impulses to the muscles, the complex neural processes involved in the co-ordination of skilled movements, and the focussing of the attention upon the work, must involve a con- siderable expenditure of nervous energy. Hence it is not sur- prising that, at the end of a day's manual work, most men not only feel tired, but are unequal to further sustained muscular or mental effort. Industrial Fatigue. The conclusion that fatigue, as observed among industrial workers, is essentially nervous in origin, is of considerable practical importance. In the first plage, it explains the mode of action of many of the factors which influence the occurrence of industrial fatigue. In the second place, it indicates the channels into FATIGUE i8i which practical efforts to prevent excessive fatigue should be directed. There appears to be no doubt (Health of Munition Workers' Committee, 191 8), that industrial fatigue is induced much more rapidly by work involving great mental concentration, and by skilled work, than by work which is more or less auto- matic and makes only slight demands upon the central nervous system. Another factor of great importance is the speed at which the work is performed. Not only is there a rate of work at which the efficiency of the individual is greatest, but also, what is probably the same thing, a rate which is least liable to cause fatigue. The optimal rate of working, as already pointed out (p. 16), is determined mainly by the natural rhythm of the nervous and muscular systems of each worker, and the policy of "speeding up" of workers is not necessarily an economical one since, by inducing excessive fatigue, it may lessen rather than increase the output of work. Further, not only the sensation of fatigue, but real (objective) fatigue, as measured by output of work, are very greatly modified by psychical processes, some, for example, the feeling of monotony, tending to hasten the onset of fatigue, others, such as " interest," improving the working capacity of the individual. Apart from the character of the work per- formed, the effect of depressing emotions, such as fear and anxiety, on the one hand, or of the stimulus of emulation or monetary considerations, on the other hand, in causing or abolish- ing fatigue is generally recognised. Finally, the general health of the individual reacts, not only upon his working powers at the beginning of the day, but also upon the rate at which his store of nervous energy becomes depleted and his output of work declines. Some degree of fatigue at the end of a day's work is a normal event and has no ill-effects, since it quickly passes off. But a characteristic feature of nervous fatigue is that the rapidity with which recovery takes place, if a man rests as soon as fatigue ap- pears, is only equalled by the slowness of recovery, if he continues working until fatigue becomes excessive. And there is a growing body of evidence that, if the working hours are too long or the conditions under which the work is carried on are unsuitable, the individual does not completely throw off the fatigue induced by each day's work, and a condition of cumulative fatigue is gradu- ally induced, which impairs his working capacity and health. In 1 82 THE PHYSIOLOGY OF MUSCULAR EXERCISE , these circumstances, not only is the output of work diminished, but the mechanical efficiency of the body declines, since even the smaller output is only maintained by an extravagant expenditure of energy. Tests of Fatigue. Fatigue to this extent is clearly undesirable in the interests both of the individual and of the community, and, in order to prevent its occurrence, trustworthy means of detecting fatigue in its earlier stages are necessary. The most satisfactory test of a man's capacity for work is his output of work, and, if a man were merely a machine, this test would be quite accurate. The out- put of work from day to day is influenced, however, by many factors other than fatigue, and these must be taken into account in the application of this test. An extremely familiar illustra- tion of the influence of extraneous factors upon a man's output of work is the difiference in output on time-work or on piece- work respectively. In the instance given in Table XLIL, the improved output at the end of the week appears to exclude fatigue as a cause of the different output in the two cases. TABLE XLII.— (From P. S. Florence.) Output of 17 Girls Drilling Fuses in Successive Weeks. (i) Time-work. (2) Piece-work. Monday .... Tuesday. Wednesday . Thursday Friday .... Average daily output 2266 2050 2037 2610 3188 2430 2567 2959 3143 3066 3291 3003 It is necessary, therefore, if the output of work is to serve as a reliable index of fatigue, to maintain uniform conditions of work, and to eliminate individual variations as far as possible by study- ing the output of groups rather than that of single workers. When these precautions have been adopted, valuable results have been obtained as to the optimal length of the working day for work of varying intensity (Vernon, 191 7). Vernon has shown very clearly that, the heavier the type of work, the shorter is the optimal length of the working day, and that, in some of the occupations which he studied, the working hours were too long. FATIGUE TABLE XLIII.— (Vernon.) 183 27 Men Sizing Fuse Bodies {Heavy Labour). Average Hours of Work per Week. Average (Relative) Output per Hour. Output per Week. Hours X Output per Hour, (i) Period of 6 weeks (2) „ „6 „ (3) >. „8 „ (4) „ ,.3 .. 61 '5 55-4 56-2 100 109 122 , 124 6150 557° 6759 6969 The results shown in Table XLIII. point to the conclusion that, at least in this particular occupation, the maximal working week, consistent with the avoidance of cumulative fa;tigue, is fifty- six hours. For lighter forms of work, Vernon found that longer hours could be worked without! loss, or even with improvement, of output. It is evident, therefore, that the establishment of a uniform length of working day for all classes of manual workers would lead in many cases to inefficiency. Earlier writers (Galbraith) had called attention to the value of one or more brief rest-periods in each day's work, as a means of lessening fatigue and improving output of work ; ar^d their results are confirmed by Vernon. The evidence, furnished by the group method, goes to show, therefore, that, when properly safeguarded and controlled, the output of work affords a satisfactory test of the conditions under which cumulative fatigue occurs and of the extent to which it is present in an individual. Since most forms of work involve the activity of the greater part of the nervous system, it might be anticipated that fatigue, induced by a particular kind of work, will extend to the nervous system as a whole. In this connection, Stanley Kent (1916) has studied the effects of industrial fatigue upon the readiness with which the individual reacts to certain sensory stimuli, and upon his acuity of sight and of hearing. His results, as a whole, ac- cord with those obtained by other methods, and indicate that, as fatigue develops, the nervous system becomes less responsive, and reacts less readily, to afferent impressions. But the subjective element enters to a considerable extent into such tests as that of acuity of vision or of hearing ; and, although, serving to indicate 1 84 THE PHYSIOLOGY OF MUSCULAR EXERCISE its presence, these tests do not necessarily give in every case a very accurate measure of the actual degree of fatigue. The Beneficial Effects of Exercise. In addition to the after-effects just described, regular exercise reacts, as every one knows, upon the whole life of the individual, since it almost always promotes, and in many people is neces- sary for, the maintenance of health, this being understood to mean not only that the various organs of the body are working normally, but also that the activities of the body are so co-ordin- ated as to bring about the highest efficiency of both mind and body. The means by which exercise brings "about these beneficial effects are numerous and not altogether clear. In all probability, one , factor is the more rapid circulation rate and the larger flow of blood and lymph through the muscles, the heart, and the brain. This will favour the more complete combustion of metabolic products and the removal of waste products, and will provide a more abundant supply of nutritive material for these organs. This factor appears, however, to be rather a subsidiary one. Violent emotion, for example, also leads to a greater flow of blood through the heart, brain, and muscles, yet few would maintain that repeated outbreaks of intense emotion are advantageous to the individual. The real value of exercise probably lies mainly in its effects upon the metabolism of the tissues themselves, and the vascular changes are useful chiefly in so far as they assist more active metabolism. The speeding up of the metabolic activity of the body, which is a characteristic feature of exercise, involves the more rapid utilisation of reserve nutritive material and prob- ably also the more complete oxidation of these materials within the cells. In this way it prevents the cells from being clogged with substances awaiting combustion, or with waste-products awaiting removal, and enables the lamp of life to burn more brightly. During exercise the additional energy provided by the in- creased chemical activity of the tissues is expended as work or heat. But, after the exercise is over, the metabolic activity of the tissues, stimulated by the exercise itself, appears to be diverted to repairing and building up the tissues. From this point of view, exercise is particularly important in youth, since it THE BENEFICIAL EFFECTS OF EXERCISE 185 is indispensable for the adequate development of the skeletal muscles, the heart, and the lungs, and, in a lesser degree, that of other structures in the body;' and the almost incessant activity in a young child is a valuable asset for its normal growth and health. How functional activity brings about growth, whereas disuse leads to atrophy, is unknown, and the nature of the pro- cesses underlying hypertrophy is still unexplained. Bradley and Taylor (19 16) have put forward the view that the H" ion con- centration within the tissues themselves is an, important factor in bringing about building up or breaking down of the tissues as the case may be. They have adduced evidence that, when the reaction of the tissues swings towards the acid side, reserve protein is transformed into " available " protein and that this undergoes autolysis. They regard it as possible that a larger blood-supply, and a more complete removal of acid products from^ the cells, may reverse this process, and may lead to the laying down of reserve protein and, therefore, to growth of the cell. This view is very suggestive, since the tissues are extremely susceptible to the reaction of the medium in which their activities are carried on ; and it seems possible that slight changes in reaction, induced by the ebb and flow of acid and basic radicles into and, out of, the tissues during and after exercise, may bring about a shifting of the point of equilibrium between autolysis on the one hand and synthesis of new tissue on the other hand. The influence of exercise upon the digestive and nervous systems is also an important element in maintaining health. The proneness of sedentary workers to suffer from dyspepsia is proverbial, and regular exercise aids digestion, partly by improv- ing the appetite, partly by assisting mechanically the passage of food along the digestive tract, and partly by its general stimu- lating influence upon metabolism. Its effect upon the central nervous system is less direct. Nevertheless, by diverting the attention into fresh channels and eliminating, for the time being, the ordinary activities of the mind, it reacts beneficially upon the mental attitude and indirectly upon the physical state of the in- dividual ; and this, at least in later life, is one of its most valu- able effects. For this reason, the character of the exercise, and the circumstances and surroundings in which it is carried out, determine in some measure its beneficial effect upon the in- dividual. 1 86 THE PHYSIOLOGY OF MUSCULAR EXERCISE In some or all of these ways, exercise improves the efficient working of the body and, what is really its counterpart, the sense of well-being and of vigour which characterise a healthy man, and both current belief and direct evidence suggest that it is conducive to long life. Anderson observed that, in Yale Uni- versity, the mortality was lower for athletes than for non- athletes. Meylan, who made a statistical study of the duration of life in a large number of Harvard oarsmen, found that the average length of life in these individuals was several years longer than the general average of the community. In drawing conclusions, however, from observations of this character it must be remembered that, in a sense, these oarsmen were selected lives since, to excel as an athlete, a man must possess from the outset a healthy body and a vigorous constitution. Summary. As a rule the circulatory and respiratory changes associated with exercise rapidly pass off after the cessation of exercise, whereas the return of the body to the resting state, as regards its metabolism, is more gradual. Fatigue after exertion is characterised by a diminished capacity for performing work, this being usually accompanied by certain subjective sensations. The sensation of fatigue does not neces- sarily correspond with the actual fatigue of an individual, when this is measured by his capacity for work. There are two types of fatigue, one originating entire' y , within the central nervous system, the other arising partly in the nervous system and partly within the active muscles. The former is of common occurrence, whereas the latter occurs com- paratively infrequently. Industrial fatigue is usually of the first type. There is no clear evidence that the products of muscular activity take any part in bringing about fatigue of the central nervous system. Exercise appears to be beneficial mainly in so far as it stimulates the metabolic activity of the tissues, thereby promoting their functional efficiency. The better blood-supply, the im- provement of digestion and other changes are also advantageous, since they favour the metabolic activities of the tissues them- selves. CHAPTER XII. THE AFTER-EFFECTS OF EXERCISE (co««KM«rf)— EFFORT-SYNDROME— OVER-STRESS OF THE HEART. There is no direct evidence that, provided a man is physically sound and in good health, exercise, however severe, is ever harm- ful or followed by serious after-effects. From time to time cases crop up in which serious ill-effects follow, and are attributed to, severe exercise. After a long cross-country run, for example, an individual, previously presumed to be healthy, may suffer, not merely from temporary collapse but from prolonged impairment of health. In some of these cases, careful investigation often reveals the existence of some hitherto unsuspected bodily defect or disease ; in others it is found that the individual has recently suffered from some infective disease. Whatever may be the aetiological factors, the harmful after- effects of exercise when they occur, and this is comparatively seldom, can almost always be referred directly or indirectly to the heart. It is not surprising that this should be the case, since one conclusion which stands out clearly as a result of the pre- ceding discussion is that the range of a man's ability to take exercise is usually determined by the functional capacity of his heart, and that the stress of exercise as a rule falls more heavily on the heart than on any other part of the body. Yet not only is the heart normally equal to the demands placed upon it, but, in a perfectly healthy man, even the most intense exertion of which he is capable has no harmful effect upon his heart. Clinical experience as a whole confirms this view, and may be summed up in Sir Clifford Allbutt's statement (1909) that "the importance of muscular effort as a factor in cardiac injury has been much ex- aggerated. In the sound adult organism the effects of physical stress on the heart are promptly counteracted by equilibrating machinery." 187 1 88 THE PHYSIOLOGY OF MUSCULAR EXERCISE Effort-Syndrome. There is abundant evidence, however, that, under certain con- ditions, severe or unwonted exercise may seriously impair the functional power of the heart, and that the lessened efficiency of the heart may then persist for weeks or months. This condition may arise suddenly as the result of a single bout of exercise in a sedentary individual or, as is more usual, may be developed gradually during the process 'of physical training or during a prolonged period of severe physical effort. Owing to the fre- quency of its occurrence among soldiers undergoing training or on active service, this condition has been termed " soldier's heart," although the manifold causes of this condition were clearly in- dicated by da Costa (1871). Moreover, as Lewis (191 7) has pointed out, it is by no means confined to soldiers, and Lewis prefers to call it " effort-syndrome," since its characteristic symp- toms appear chiefly during exercise. The essential features of effort-syndrome are, first, lessened ability to perform muscular.work, and, second, an exaggeration of the normal response of the circulatory and respiratory systems to exercise. If, for example, a healthy man and a patient suffering from effort-syndrome perform the same amount of exercise, the dyspnoea is greater and the pulse-rate and blood- pressure are higher in the patient than in the healthy man. Further, the pulse returns to its resting level after exercise much more slowly in cases of effort-syndrome than in health. When the patient is resting the pulse-rate and respiration are often normal, though some increase in pulse-rate and some degree of hyperpncea may be present. Exhaustion, headache, palpitation, tachycardia, precordial pain, giddiness, and fainting are common. The condition exhibits all grades of severity, some patients displaying symptoms only when subjected to severe exercise, whereas, at the other end of the scale, are those who, even in bed, are breathless and have a frequent pulse. The extremely varied aetiology of effort-syndrome at once suggests the possibility that these cases are not all of one type and that the morbid, or at least abYiormal, process, responsible for the symptoms grouped under this title, is not the same in every case. Indeed it is possible that each of the explanations offered as to the cause of effort-syndrome may be true for particular EFFOR T-S YN DROME 1 89 cases. In " gassed " men, for example, the symptoms could be accounted for by the existence of some change in the pulmonary epithelium, not necessarily of a gross nature, but sufficient to lessen the rate at which oxygen can diffuse into the blood. Again, many patients with effort-syndrome display marked hyper- excitability of the central nervous system ; and over-activity of the medullary centres, either as a direct result of greater ex- citability of these centres, or brought about by exaggerated im- pulses from the higher parts of the brain, would explain the excessive circulatory and respiratory response to exercise ex- hibited by these patients. The view that abnormal excitability of the nervous system is the primary cause of effort-syndrome, and that the condition is purely nervous in origin, has been ac- cepted by some writers, who apparently hold that effort-syndrome either arises as the outcome of some shock to the nerve-centres in a neurotic subject or is simply a special manifestation of neuras- thenia (Abrahams). Although this may be the true explanation of some cases of effort-syndrome, there is evidence that, even among soldiers on active service, many of the patients suffering from effort-syn- drome are in no way neurasthenic (W. E. Hume). Moreover, effort-syndrome occurs frequently in civil life under conditions in which a purely nervous origin can almost certainly be excluded. Lewis considers that as a rule over-excitability of the nervous system is not the primary factor in the causation of the symp- toms of effort-syndrome, but is merely a manifestation of an underlying generalised disorder of metabolism or of actual in- toxication of bacterial origin. He concludes that the symptoms may be caused " either by toxic products of bacterial origin or perhaps more often by the products of faulty metabolism induced by infectious disease ". In default of any evidence of organic de- fect or disease of the myocardium, Lewis appears to regard the metabolism as a whole as being thrown into disorder, there- by bringing about certain changes in the body which are im- mediately responsible for the symptoms manifested by these patients. The arguments adduced in support of this view are, first, the close relationship between bacterial infection and effort- .syndrome, second, the diminution or disappearance of symptoms when the source of infection is removed, and, third, the presence of certain changes in the blood and urine of the patients. 190 THE PHYSIOLOGY OF MUSCULAR EXERCISE The belief that the character of the blood is altered in effort- syndrome rests almost entirely on the evidence brought forward by Barcroft, Cotton, Lewis, Milroy, Dufton, and Parsons (1916) that the extreme breathlessness on slight exertion, which is so characteristic of this condition, is due to a deficiency of buffer salts in the' blood. Examining in vitro the blood of such patients, they found (i) that, when all the carbonic acid was shaken out of the blood, its reaction became slightly more alkaline than that of normal blood ; (2) that, when it contained the amount of carbonic acid normally present in the body, it was just on the acid side of normal ; (3) that any further addition of carbonic acid increased the H' ion concentration of the blood to an abnormal degree. The reaction of the blood was apparently determined by noting the form of its dissociation curve in the various conditions just mentioned. In one instance these observations were confirmed by direct determination, by means of the gas electrode, of the effect upon its reaction of adding carbonic acid to normal blood and to that of patients. Further, it was found that, when small amounts of di-sodium phosphate and sodium bicarbonate were added to blood obtained from the patients, this behaved like that of a normal person as regards the change in its reaction produced by the addition of carbonic acid. The deduction drawn from these experiments is that, owing to the deficiency of buffer salts, the normal passage of lactic and carbonic acids into the blood from the active muscles during exercise increases the H" ion concentration of the blood, and therefore the respiratory movements, to an abnormal extent. Barcroft and his co-workers do not suggest, however, that a de- ficiency of buffer salts is resp6nsible for the circulatory phenomena of effort-syndrome. It is extremely difficult to reconcile this conclusion with the current view of the means by which the reaction of the blood is controlled and of the part played by the so-called buffer salts in determining its reaction. It has been shown (p. 30) that the re- H CO action of the blood is represented by the equation C„ = K ^ J^ , NaHCOg and, as Bayliss has pointed out, the only buffer salt, and indeed the only effective buffer substance of any practical importance, in blood-plasma is sodium bicarbonate. It is clear, therefore, that, when carbonic acid is removed from the blood, a de- EFFOR T- S YNDR OME 191 ficiency of sodium bicarbonate would render the blood less alkaline than normal blood, and that the observation of Lewis and his colleagues is not merely incompatible with a deficiency of buffer salts but suggests that the blood of their patients con- tained more bicarbonate than usual. It is in any case almost impossible to imagine how a deficiency of buffer salts could render the patient's blood more alkaline in the absence of car- bonic acid, and more acid in the presence of carbonic acid, than normal blood. Again, Drury has found that the tension of carbonic acid in the alveolar air of cases of effort-syndrome during rest is within the normal range (an observation which Bainbridge has confirmed). Since, in Bainbridge's cases, the patients were not breathless when resting, the H' ion concentration of their blood must have ^ been normal, unless the respiratory centre was less sensitive than usual, and, consequently, the third term of the equation, namely, the bicarbonate of the plasma must also have been normal in amount. That this is actually the case in some patients has been shown by direct measurement of the plasma- bicarbonate by the Van Slyke method. Bainbridge and Canti examined the blood of three patients,^ who were resting in bed and not breathless, and obtained normal figures for their plasma- bicarbonate. TABLE XLIV.— (Bainbridge and Canti.) Case. Volume of CO2 obtained from Plasma. 64-2 6i-3 62 '3 The normal range is from 5s to 75 volumes. One control yielded 62 volumes of CO,. The conclusion appears inevitable that the blood of patients suffering from effort- syndrome is not lacking in sodium bi- carbonate, and that the observations of Lewis, Barcroft, and their co-workers must be capable of some other interpretation than ' Dr. J. H. Drysdale very kindly allowed us to examine these patients who were under his care. 192 THE PHYSIOLOGY OF MUSCULAR EXERCISE that which they offer. It is perhaps significant that the method adopted for determining a change in the reaction of the blood is an indirect one, namely, the affinity of haemoglobin for oxygen. It has been pointed out earlier (p. 36), however, that the Barcroft-Peters curve which expresses the relationship between the affinity of haemoglobin for oxygen and the H ' ion concentra- tion of the plasma is not constant for all individuals or under all conditions. It is possible, therefore, that, in patients suffering from effort-syndrome, the normal equilibrium between the re- action of the red cells and that of the plasma may be disturbed. The Circulatory Hypothesis. In view of the evidence that the buffer salts, or at least, the bicarbonate, of the blood are not deficient, it seems necessary to look elsewhere for an explanation of the exaggerated circulatory and respiratory response to exercise which is so characteristic of effort-syndrome. Accepting Lewis' view that the primary cause of the symptoms is either toxic products of bacterial infection or products of faulty metabolism induced by infectious disease, there is clearly more than one point at which such products might exert their injurious influence. And the possibility at once presents itself that these may originate in some primary defect or impairment of the adjustments of the circulatory system normally occurring during exercise. From this point of view the following tables, which illustrate the effect of exercise upon the pulse-rate in the trained man, the untrained nian, and the patient with effort-syndrome, are suggestive : — TABLE XLV.— Pulse-Rate per Minute in Effort-Syndrome. (Meakins and Gunson.) Pulse-rate during Rest. ' Just after Exercise. Time of Decline. A verage figures — 1I 10 Healthy subjects . (2) iS Patients presenting no material 75 109 I minute symptoms after exercise , (3) 21 Patients presenting symptoms after exercise .... 79 • 99 120 ISO I » 5 minutes The exercise consisted in climbing at a brisk walk a of decline = time taken for return of the pulse-rate to \ value before the exercise. group of 27 steps. Time vithin 5 beats of the resting EFFORT-SYNDROME TABLE XLVI. — Healthy Men. Pulse-Rate Before and After Exercise (J Mile Run). (Pembrey and Cook.) 193 Rest. Just after Exercise. Counted during 1st Minute. Counted in First Four Successive Periods of 13 Seconds. I s 3 4 Trained Untrained . 76 80 l5o 180 .135 165 40 .45 35 41 31 40 29 39 It is clear that, as regards their response to exercise, a man suffering from effort-syndrome bears almost the same relation to a healthy untrained man that the latter does to a trained man. The same relationship appears to hold good for the blood- pressure and probably also for the pulmonary ventilation. Every gradation exists between the fully trained man on the one hand and the patient suffering severely from effort-syn- drome on the other hand; and, whereas the trained man is more efficient than the average man, the patient with effort- syndrome is less completely equipped than the average man for the stress of ordinary life. It seems justifiable, therefore, to apply to the patients, in considering the causation of their symptoms, the conclusions which have already been reached as to the effect of training upon the circulatory response to exercise. The trained man takes exercise with less circulatory and re- spiratory stress than the untrained man, chiefly because of the greater contractile power of his heart, and the suggestion natur- ally presents itself that, in the patient who displays during exer- cise the exaggerated respiratory and circulatory response known as effort-syndrome, the contractile power of the heart is less than normal. Alike in the trained man, the untrained man, and the patient with effort-syndrome, the heart possesses only two means of increasing its output in response to a larger venous inflow during exercise. These are dilatation of the heart, with a corresponding increase in its contractile power, and greater frequency of the beat. If the nutrition of the heart is normal, and the diastolic length of the fibres is the same in each case, the heart of the trained man contracts more strongly at each beat than that of the untrained man solely because its fibres are larger and more numerous, or in other words because it is more muscular. The 13 194 THE PHYSIOLOGY OF MUSCULAR EXERCISE stronger contraction enables the heart to empty itself more com- pletely, and to maintain a given output with a slower pulse-rate, than the heart of the untrained man. In the same way if, either because it is less muscular or because the nutrition of its fibres is impaired, the contractile power of a man's heart becomes less than that of the heart of a healthy untrained man, then, assuming the same venous inflow in the two cases, the feebler heart will discharge less blood into the aorta at each beat than the normal heart. In order to maintain the same output per minute as the normal heart, the feebler heart must either beat more frequently or dilate more than the normal heart. The less its coiitractile power the greater will be the dilatation of the heart and the frequency of the pulse necessary to bring about a given output per minute; arid, if it is very feeble, the heart, even on slight exertion, may keep up a norma) output only when it is dilated almost to its physiological limit in order to obtain its maximum contractile power and when it is ^beating abnormally frequently. Hence, in a group of individuals, performing the same amount of muscular work, the extent to which the heart dilates and the pulse accelerates in each in- dividual is a measure of the contractile power of his heart, pro- vided that extraneous emotional factors are excluded. By the application of such a test, a trained man could be picked out from among a group of untrained men, and this test is actually used, as regards the pulse-rate, as one method of ascertaining the severity of the condition of effort-syndrome. Observations made by the orthodiagraphic method led Lewis to the conclusion that, in his patients, the size of the heart during rest was certainly not greater, and on the average slightly less, than that of healthy young individuals, although he qualifies this conclusion by noting, first, that in the patients the pulse- rate was rather frequent, this tending to reduce the size of ' the heart, and, secondly, that most of the patients had been in a sedentary occupation for the greater part of their lives. Using the same method, Meakins and Gunson were unable to find any change in the size of the heart during exercise, al- though the normal decrease just after exercise was absent in severe cases of effort-syndrome. The limitations of the ortho- diagraphic method have already been discussed (p. 60) ; and, since Lewis apparently regards a difference of less than 5 mm. EFFORT-SYNDROME 195 as being within the limits of experimental error, his observations are not incompatible with the conception of effort-syndrome, now under consideration. In a healthy man, the co-ordinating mechanisms concerned in bringing about the normal correspondence between the degree of muscular activity and the pulmonary ventilation and circula- tion are extremely efficient ; and it is probably only during in- tense exertion that an inadequate supply of oxygen to the brain and other tissues becomes an active factor in intensifying the respiratory and circulatory changes accompanying exercise. If, however, the contractile power of the heart is impaired, its efficiency as a pump falls off ; and inefficiency of the most vital part of the mechanism concerned in supplying oxygen to the body during exercise, not only lessens the amount of work which a man can perform in a given time, but throws into disorder the co-ordination normally maintained between the demand for and the supply of oxygen. In consequence, the supply of oxygen to the active organs during exercise never quite keeps pace with the needs of the body ; and, either because the medullary centres are not fully supplied with oxygen, or because the oxidation of lactic acid in the muscles falls abnormally short of its production and the H' ion concentration of the blood becomes excessive, the activity of the respiratory and vaso-motor centres is ex- aggerated and the pulse accelerates still further. According to this conception, the exaggerated circulatory and respiratory response, observed not only in effort-syndrome, but also during exercise at high altitudes, possesses the same signifi- cance, since it is the only means of preserving the normal relation- ship between the demands of the active organs for oxygen and the supply of oxygen, and of preventing a serious deficiency in the supply of oxygen. If this explanation of their causation is accepted, the symptoms characteristic of effort-syndrome merely furnish a further illustration of the idea, underlying all the pre- ceding discussion, that, in the last resort, the requirement of the tissues for oxygen brings into action the mechanisms concerned in meeting that need. Etiology of Effort-syndrome. What, then, are the grounds for believing that, in patients with effort-syndrome, the nutritive condition of the cardiac muscular 13* 196 THE PHYSIOLOGY OF MUSCULAR EXERCISE fibres, and hence the power of the heart to develop energy, is impaired or at least inferior to that existing in the normal heart ? The most important predisposing cause of the condition is infection. Lewis considers that, in at least 50 to 60 per cent, of his cases, " infectious disease may be held to play a chief part in promoting the disease (effort-syndrome) in its initial stages ". If already present, the condition is exacerbated by an inter-current infection. The tendency of infective disease to injure the heart is notorious, the dama'ge being often manifest as cloudy swelling, fatty change, or cellular infiltration ; and there can be no doubt that, short of these relatively gross changes, the nutritive con- dition, that is to say, the metabolic activity of the heart-muscle, may be gravely impaired. In the case of the heart, as of every organ, impaired nutrition means lessened functional capacity, and this may arise either from a smaller power to store up potential energy or from an inability to convert this effectively into kinetic energy. In these circumstances the contractile power of the heart, or, in other words, the energy set free at each beat, will be abnormally small. Extremely little is known concerning the nature of the meta- bolic changes which underlie what is termed the nutritive con- dition of an organ. But it is conceivable, for instance, either that the power of the muscle-fibres to take up into their substance the oxygen reaching them by diffusion may be impaired or that the normal oxidative processes may be carried out less completely or less rapidly. Some colour is lent to this suggestion, first, by the well-known action of many bacterial toxins in diminishing oxidative changes in the body, and, second, by the evidence of Krogh and Lindhard that the efficiency of the oxidative mechan- ism for lactic acid in muscle varies in different individuals. A change of this kind, assuming it to occur in cardiac muscle, would at once disturb the normal relationship between the production and destruction of lactic acid ; and during exercise, though not necessarily during rest, the heart would tend to become rapidly fatigued and clogged by the accumulation of lactic acid, and possibly other metabolic products, within its fibres. The readiness with which the contractile power of the heart is affected by disturbance of its nutrition may be observed under experimental conditions; Starling found that, when the heart EFFOR T-S YNDROME 1 97 was fatigued or its supply of oxygen not quite adequate, its contractile power rapidly diminished. It is easy to understand, therefore, how an intoxication of bacterial origin, and perhaps especially a chronic intoxication, may bring about an impairment of the nutritive state of the heart musclg, though, unless the in- dividual takes an amount of exercise to which the heart is unac- customed, this may not only escape notice, but may eventually disappear, since the effect of infection upon the nutrition of the heart is usually transient. Apart from infection, the large proportion of cases of effoit- syndrome occurring amongst men normally engaged in sedentary work is very striking. Lewis notes that many of the patients found by experience that they were always unable to take violent exercise, although they were quite well when engaged in seden- tary work. One is tempted to suggest that in these patients the nutritive level and inherent power of the heart muscle (and also their skeletal muscular development) are below the average just as that of other men is believed to be above the average, and that, in many cases, the patient with effort-syndrome, like the athlete, is born and not made. Under the ordinary conditions of life these men pass muster, but, when brought to the test df active physical training under military conditions or when subjected to unwonted stress, they fall into the hands of the physician and are labelled effort-syndrome. Many of Lewis' patients, however, had adopted a sedentary life from choice and not from necessity ; and it may be that, as Lewis suggests, a sedentary life in itself provides the conditions which predispose to effort-syndrome. If this is the case, a seden- tary life will naturally accentuate any inborn deficiency in the contractile power of the heart. It appears probable, then, that this condition is not a disease but a disability, which may be temporarily produced by infection (and by other means), or may be present from birth, or may be the outcome of a habitually sedentary existence. That its prim- ary cause is impairment of the contractile power of the heart muscle is suggested not only by the reasons already advanced but by the fact that it is most effectively treated by carefully graduated exercise carried out under proper supervision. This has long been an accepted form of treatment jn cases of myo- cardial defect. 198 THE PHYSIOLOGY OF MUSCULAR EXERCISE Over-stress of the Heart. Whatever may be the case in effort-syndrome, there is no doubt that, in some circumstances, a single bout, or repeated bouts, of violent exertion may be followed not only by prolonged, or even permanent, inability to take active exercise, but also by pathological dilatation of the heart or other signs of myocardial defect. This condition, often termed over-stress of the heart, may arise in young subjects when exercise is taken during the course of, or shortly after the cessation of, an infection, or in middle life when the heart is presumed to have lost its early vigour. The character of its predisposing causes indicates that some lowering of the nutritive condition of the heart muscle "is a prerequisite to its occurrence, and it seems clear that severe exer- cise, though not injurious to a healthy heart, may actually damage the heart when this is already less efficient than a normal heart. Many writers consider that the damage to the heart consists, in the slighter cases, in fatigue and loss of tone of the cardiac muscle, whereas, in the severe cases of over-stress, there occurs an actual strain of the muscle fibres, these being mechanically stretched beyond the limits of their elasticity. Such a strain, by altering the molecular condition of the fibre, permanently changes its molecular structure (Clifford Allbutt). On this view, fatigue and loss of tone result'in passive but remediable dilatation, whereas the altered molecular state of the strained fibres leads to irremediable dilatation. In this connection the expression " loss of tone'' is used by clinical writers (Clifford Allbutt, J. Mackenzie) to mean loss of diastolic tone. The evidence previously brought forward (p. 47) goes to show, however, that the normal heart does not possess diastolic tone ; and, since the heart cannot lose what it has never possessed, loss of diastolic tone is not the cause of dilatation of the heart. The essence of the recent work of Patterson, Piper, and Starling, at least as regards its application to such conditions as that under consideration, is that in itself dilatation of the heart is not harmful but advantageous. The fatigued heart dilates, not because its muscular wall yields more easily before the inflowing blood during diastole but because its contractile power is weakened and only by dilatation can its contractile power OVER-STRESS OF THE HEART 199 be increased in accordance with the law of the heart. But the term "tone," as applied to the heart, does acquire a definite meaning if it is used to express the amount of energy which the cardiac fibres can develop during systole, or, in other words, the functional capacity of the heart for any given diastolic volume. According to this definition, loss of tone means feebler contrac- tion of the cardiac muscle during systole ; and the atonic heart dilates in order to develop more energy, since dilatation increases, instead of lessening, the power of the heart to carry on the cir- culation. The milder forms of heart-stress (remediable dilatation) may, therefore, be fully explained as being the outcome of extreme and prolonged fatigue, and hence of diminished contractile power, of a heart already predisposed to fatigue by the ill-effects of recent infection, or of the other causes already considered, upon its nutritive condition. The occurrence of molecular alteration of the muscular fibres as a result of mechanical stress is obviously very difficult either to prove or to disprove. But the pathological dilatation of the heart, which may be a sequence of exercise carried out under the conditions already described, clearly implies the existence of son?e change — not necessarily structural — in the muscle of the heart. The suggestion that strain of the muscular fibres, by alter-; ing their elastic state, allows the heart passively to dilate to excess, may appear to provide an adequate explanation of the dilatation and at the same time to place it in the category of pathological rather than physiological dilatation. This hypothesis fails to take account of the facts that, unless the pericardium has given way, the mechanical efficiency of the heart is in no way lessened when its fibres are stretched during diastole to the limit allowed by the normal pericardium, and that the mechanical stress imposed upon the heart during exercise is not necessarily greater in the man who develops symptoms of over-stress than in the man whose heart remains normal. It might be argued that a degree of stretching, which would not harm normal cardiac muscle, might damage an ill-nourished heart. But, since the normal heart is completely relaxed during diastole, and its filling even to the physiological limit depends upon the venous inflow, any loss of elasticity on the part of its fibres would not influence its diastolic filling. 20O THE PHYSIOLOGY OF MUSCULAR EXERCISE The hypothesis that intra-molecular changes in its fibres lead to dilatation of the heart by allowing it to fill to an abnormal extent during diastole under a given venous pressure appears, therefore, to be incompatible with the principles which underlie the filling of the heart. Any such change, assuming it to occur, must disturb not the filling but the emptying of the heart, since it lessens the ability of the cardiac muscle to develop energy or to transform energy into effective mechanical work. None the less, it seems quite conceivable that some subtle alteration in the structure of the delicate muscular machine might take place as a result of mechanical stress, and that such a change might interfere with the normal transformations of energy of which visible con- traction is the outward sign. It is equally possible, however, that the stress might throw out of gear the chemical rather than the physical basis upon which this transformation of energy depends. Whether structural or chemical in origin, the essential feature of over-stress is clearly lessened contractile power of the heart. The less its contractile power, the more must the heart dilate in order to obtain the energy necessary to maintain its output. If the power of the heart sinks to a level at which it can barely maintain the output necessary during rest, the heart will remain fully dilated long after exercise, and, under the steady pressure of the heart on the pericardium, the latter will give way. Further dilatation of the heart is then possible, but, with the yielding of the pericardium, the heart has crossed the border-line between physiological and pathological dilatation, since its mechanical efficiency has begun to decline. It appears probable, then, that the principles, which underlie the working of the normal heart, also hold good for the behaviour of the heart during over-stress ; and the application of these principles to other forms of cardiac disease, involving the myo- cardium, would probably be very fruitful since, as Sir Clifford AUbutt has said, " To go with physiology as far, as we can is not only to tread so far on irelatively firm ground, but also to provide a discipline and a preciser terminology". Summary. There is no evidence that, in a perfectly healthy man, even the most intense exertion produces any harmful effect upon the heart. SUMMARY 20I The term effort-syndrome is applied to a condition arising as the result of severe exercise or in the course of physical train- ing, and characterised by a lessened capacity to perform muscular work and by exaggeration of the respiratory and circulatory changes normally occurring during exercise. The view that the respiratory symptoms are dependent upon a deficiency of buffer salts in the blood in patients sufferings from effort-syndrome is discussed, and reasons are given for not accepting this view. The conclusion is reached that, in effort-syndrome, the con- tractile power of the heart is below the average, that, for this reason, either the muscles or the nervous system suffer from a slight deficiency of oxygen during exercise, and that the ex- aggeration of the respiration, pulse-rate, and blood-pressure is the outcome of an inadequate supply of oxygen to the active tissues. The most . important aetiological factors which cause effort- syndrome are, first, infective disease, and, second, a sedentary mode of life. If the nutritive condition of the heart is impaired, violent exertion may be followed, not only by prolonged inability to take severe exercise, but also by pathological dilatation of the heart or by other signs of myocardial defect. This constitutes over-stress of the heart. The primary change in over-stress of the heart is lessened contractile power of its fibres, this being due in the milder cases to fatigue of the cardiac muscle, and in the more severe cases possibly to some chemical change in the fibres which lessens their power to develop energy. The dilata- tion of the heart is a secondary compensatory process, which enables the heart (in accordance with the law of the heart) to increase its contractile power by greater diastolic length of its fibres. It is not due to loss of diastolic " tone," since such tone does not exist even in the normal heart. If the pericardium yields, thereby allowing the heart to dilate still further, the dilatation becomes pathological, because it is then accompanied by lowered mechanical efficiency of the heart. BIBLIOGRAPHY. Abraham, A. (1917). — " Soldier's Heart." Lancet, I, p. 442. Allbutt, Sir Clifford (1909).— " Over-stress of the Heart." A System of Medicine, edited by Sir Clifford Allbutt and H. D. RoUeston, vol. 6, pp. 193-253- Anderson (1912). — Medical Times, New York. Anrep, Q. von (1912). — "On the Part Played by the Suprarenals in the Normal Vascular Reactions of the Body." Journ. of Physiol., vol. 45, P- 307- (1912). — "On Local Vascular Reactions and their Interpretation." Journ. of Physiol., vol. 45, p. 318. Araki, T. (1894). — "Ueberdie chemischen Aenderungen der Lebensprocesse in Folge von Sauerstoffmangel." Zeitschr. f. Physiol. Chem., vol. 19, p. 422. Asher, L. (1910). — "Die innere Sekretion der Nebenniere und deren In- nervation." Zentrabl. f. Physiol., xxiv, p. 927. (1912). — Zeitschr. f. Biol., vol. 58, p. 274. Atwater, W. O., and F. Q. Benedict (1903).— "Experiments on the Meta- bolism of Matter and Energy in the Human Body." U.S. Dep. of Agriculture, Bulletin No. 136. Aulo, T. A. (191 1). — " Weiteres uber die Ursache der Herzbeschleunigung bei der Muskelarbeit." Skand. Arch. f. 'Physiol., vol. 25, p. 347. Bainbridge, F. A. (1914). — " On some Cardiac Reflexes." Journ. of Physiol., vol. 48, p. 332. (1915). — "The Influence of Venous Filling upon the Rate of the Heart." Journ. of Physiol., vol. 50, p. 65. and R. Hilton (1919). — "The Relation between Respiration and the Pulse-Rate." Proc. Physiol. Soc, p. Ixv in/. Physiol., vol. 52. and J. W. Trevan (1917). — "Some Actions of Adrenalin upon the Liver.'' Journ. of Physiol., vol. 51, p. 459. Barcroft, J. (19 14). — "The Respiratory Function of the Blood." Camb- Univ. Press. and M. Camis (1909). — " The Dissociation Curve of Blood." Journ. of Physiol., vol. 39, p. 118. C. Q. Mathison, H. Roberts, and J. H. Ryffel (191 5).— "Re- port of the Monte Rosa Expedition of 191 1." Phil. Trans, of the Royal Society, B, vol. 206, p. 49. and W. E. Dixon (1907). — "The Gaseous Metabolism of the Mam- malian Heart." Journ. of Physiol., vol. 35, p. 182. and A. V. Hill (1909). — "The Nature of Oxyhsemoglobin with a Note on its Molecular Weight." Journ. of Physiol., vol. 39, p. 411. 203 204 THE PHYSIO]LOGY OF MUSCULAR EXERCISE Barcroft, J., and H. Piper (1912).— "The Gaseous Metabolism of the Sub- maxillary Gland, with Especial Reference to the Effect of Adrenalin and the Time-Relation of the Stimulus to the Oxidation Process." Joum. of PkysioL, vol. 44, p. 359. Bardswell, N. D., and J. E. Chapman (igu). — " Some Observations upon the Deep Temperature of the Human Body at Rest and After Mus- cular Exertion." Brit. Med. Joum., vol. i, p. 1106. Barnard, H. L. (1898).— "The Functions of the Pericardium." Proc. Physiol. Soc. m/oum. of Physiol., vol. 22, p. xliii. Bayliss, W. M. (1901).— "The Action of Carbon Dioxide on Blood- vessels." Proc. Physiol. Soc. xafoum. cf Physiol., vol. 26, p. xxxii. (1915). — "The Principles of General Physiology," pp. 447-448. (1918). — "Intravenous Injection and Wound-Shock." [Longmans, Green & Co.] (1919)- — "Traumatic Toxsemia," Memorandum No. 7 of the Shock Committee. [Issued by Med. Res. Comm.] Benedict, F. Q., and E. P. Catlicart (i 913).— "Muscular Work. A Metabolic Study, with Especial Reference to the Efficiency of the Human Body as a Machine." Published by Carnegie Institution of Washington. No. 187. and E. P. Jo^lin (1910). — "Metabolism in Diabetes Mellitus." Pub- lication No. 136, Carnegie Institution, Washington, p. 166. — — and H. M. Smith (191 5).— "The Metabolism of Athletes." Journ. of Biol. Chem., vol. 20, p. 243. Blix, Magnus (1891). — "Die lange under die Spannung des Muskels." Skand. Arch.f. Physiol., vol. 3, p. 295, and vol. 5, p. 150. (1903). — "Zur Frage iiber die Menschliche Arbeitskraft." Skand. Arch.f. Physiol., vol. 15, p. 122. Bohr, Ch., and V. Henriques (1897). — " Recherches sur le lieude la con- sommation de I'oxyg^ne et de la formation de I'acide carbonique dans I'organisme." Archiv. de Physiol., vol. 9, pp. 459, 590, 710, 819. Boothby, W. M. (1915). — " Determination of the Circulation Rate in Man at Rest and at Work." Amer. Journ. of Physiol., vol. 37, p. 383. and F. B. Berry (191 5). — "Effect of Work on the Percentage of Haemo- globin and Number of Red Corpuscles in the Blood." Amer. Joum. of Physiol., vol. 37, p. 378. Bowen, W. P. (1904). — "Changes in Heart-rate, Blood-pressure, and Dura- tion of Systole Resulting from Bicycling." Amer. Joum. of Physiol., vol. II, p. 59. Boycott, A. E., and J. S. Haldane (1905).— "The Effects of High Ex- ternal Temperature on the Body-temperature, Respiration and Circula- tion in Man." Proc. Physiol. Soc. vajoum. of Physiol., vol. 33, p. xii. (igo8). — " Respiration and Low Pressures." Joum. of Physiol., vol. 37, P- 355- Bradley, H. C, and J. Taylor (1916).— "Studies of Autolysis, III. The Effect of Reaction on Liver Autolysis." Joum. of Biol. Chem., vol. 25, p. 261. Buchanan, Florence (1909). — "The Physiological Significance of the Pulse Rate." Trans. Oxford University Scientific Club, No. 34, p. 351. Biirgi, E. (1900). — "Der respiratorische Gaswechsel bei Ruhe und Arbeit auf Bergen." Archiv. f Physiol.,^. 509. BIBLIOGRAPHY 205 de la Camp (1903-4). — " Experimentelle Studien iiber die acute Herzdilata- tion." Zeitschr.f. Klin. Med., vol. 51, p. i. Campbell, J. M. H., C. Q. Douglas, and F. Q. Hobson (1914).— "The Response of the Respiratory Centre to Carbon Dioxide, Oxygen, and Hydrogen Ion Concentration." fourn. of Physiol., vol. 46, p. 301. Cannon, W. B. (1914). — "The Emergency Function of the Adrenal Medulla in Pain and the Major Emotions." Amer.J. Phys., vol. 33, p. 356. (1915)- — "Bodily Changes in Pain, Hunger, Fear, and Rage."^'fD. Appleton & Co.] and D. de la Paz (1910). — "Emotional Stimulation of Adrenal Secre- tion." Amer. Joum. of Physiol., vol. 28, p. 64. and R. Q. Hoskins (1911). — "The Effects of Asphyxia; Hyperpncea, and Sensory Stimulation on Adrenal Secretion." Amer. Joum. of Physiol., vol. 29, p. 275. and L. B. Nice (1913). — " The Effect of Adrenal Secretion on Muscular Fatigue." Amer. Joum. of Physiol., vc\.y2,^. ^\. \ Cathcart, E. P., and Q. H. Clarke (1913).— "The Influence of Carbon Dioxide on the Heart in Varying Degrees of Anassthesia." Joum. of Physiol., vol. 47, p. 393. E. L. Kennaway, and J. B. Leathes (1908). — "The Origin of Endogenous Uric Acid." Quarterly Joum. of Med., voi. i, p. 416. Chauveau, A. (1896). — "Source et nature du potentiel directement utilis6 dans le travail musculaire, d'apr^s les ^changes respiratoires, chez rhomme en dtat d'abstinence." Comptes Rendus de VAcad. des Sciences, vol. 122, p. 1163. and Kaufmann (1887). — " De I'activitd nutritive et respiratoire des musclqp qui fofictionnent physiologiquement sans produire de travail m^canique." Comptes Rendus del' Acad, des Sciences,\o\. 104, p. 1763. Christiansen, J., C. Q. ^Douglas, and J. S. Haldane (1914).— "The Ab- sorption and Dissociation of Carbon Dioxide by Human Blood." Joum. of Physiol., vol. 48, p. 244. Cotton, T. If., T. Lewis, and D. L. Rapport (1917).—" After-effects of Ex- ercise on Pulse-rate and Systolic Blood-pressure in Cases of ' Irritable Heart'." Heart, vol. 6, p. 269. Da Costa, J. M. (1871). — "On Irritable Heart." Amer. Joum. Med. Sciences, vol. 6i, p. 17. Dale, H. H., and A. N. Richards (191 8).— "The Vasodilator Action of Histamine and of some other Substances." Journ. of Physiol., vol. 52, p. no. Determann (1906). — "Klin, Untersuch. u. d., Viskositat des Menschliche Blutes." Zeitschr. f. Klin. Med., vol. 59, p. 283. Douglas, C. Q., and J. S. Haldane (1909). — " Cheyne-Stokes Breathing.'' Joum. of Physiol., vol. 38, p. 401. (1909). — " Regulation of Breathing." Joum. of Physiol., vol. 38, p. 420. (1909)- — "The Effects of Previous Forced Breathing and Oxygen In- halation on the Distress Caused by Muscular Work." Proc. Physiol. Soc. \n Journ. of Physiol., vol. 39, p. i. -^ Y. Henderson, and E. C. Schneider (1912).— "Physiological Observations made on Pike's Peak, Colorado, with Special Reference to Adaptation to Low Barometric Pressures." Phil. Trans. Roy. Soc, B, vol. 203, p. 185. 2o6 THE PHYSIOLOGY OF MUSCULAR EXERCISE Drury, A. N. (19 17).—" Report upon Soldiers Returned as Cases of 'Dis- ordered Action of the Heart' (D.A.H.) or 'Valvular Disease of the Heart' (V.D.H.)," p. 18. [Medical Research Committee.] Special Report, No. 8. Durig:, A. — " Physiol. Ergebnisse der in Jahre 1906 durchgefiihrten Monte Rosa Expedition, p. 41." Denkschr. d. Wiener. Kais. Akad. d. Wissensch. Math. Naturw. Kl. - — and N. Zuntz (1904). — "Physiologic des Menschen im Hochgebirge." Archiv.f. Physiol., Suppl., p. 417. Elliott, T. R. (1912).— "The Control of the Suprarenal Glands by the Splanchnic Nerves." Joum. of Physiol., vol. 44, p. 374. Evans, C. Lovatt (1912). — "The Gaseous Metabolism of the Heart and Lungs." Joum. of Physiol., vol. 45, p. 213. (1914)- — "The EJflfect of Glucose on the Gaseous Metabolism of the Isolated Mammalian Heart." Joum. of Physiol., vol. 47, p. 407. (1917). — " The Mechanism of Cardiac Acceleration by Warmth and by Adrenalin." Joum. of Physiol., vol. 51, p. 91. - — (1918). — " The Velocity Factor in Cardiac Work." fount, of Physiol., vol. 52, p. 6. and Y. Matsuoko (191 5). — "The Effect of Various Mechanical Con- ditions upon the Gaseous Metabolism and Mechanical Efficiency of the Mammalian Heart." Joum. of Physiol., vol. 49, p. 378. and S. Ogawa (1914). — "The Effect of Adrenalin on the Gaseous Metabolism of the Isolated Mammalian Heart." Journ. of Physiol., vol. 47, p. 416. — andE. H. Starling (1913).— "The Part Played by the Lungs in the Oxidative Processes of the Body." Joum. of Physiol., vol. 46, p. 413- Pletclier, W. Morley (1902). — "The Relation of Oxygen to the Survival Metabolism of Muscle." Joum. of Physiol., vol. 28, p. 474. (I9I3)- — " Lactic Acid Formation, Survival Respiration and Rigor Mortis in Mammalian Muscle." Joum. of Physiol., vol. 47, p. 361. and Q. M. Brown (1914). — "The Carbon Dioxide Production of Heat Rigor in Muscle and the Theory of Intramolecular Oxygen." .foum. of Physiol., vol. 48, p. 177. and F. Q. Hopkins (1907). — " Lactic Acid in Amphibian Muscle." Joum. of Physiol., vol. 35, p. 247. (1917)- — "fhe Respiratory Process in Muscle and the Nature of Muscular Motion." Croonian Lecture. Proc. Roy. Soc, B, vol. 89, p. 444- Frumerie, K. (1913).- — " Ueber das Verhaltnis der Ermiidungsgefiihls zur CO, — abgabe bei statischer Muskelarbeit." Skand. Arch. f. Physiol., vol. 30, p. 409. Oaskell, W. H. (1878). — "Investigations on the Vaso-motor Nerves of Striated Muscles." Joum. of Physiol., vok i, p. 108. (1879). — "Further Researches on the Vaso-motor Nerves of Ordinary Muscles.'' Joum. of Physiol., vol. i, p. 262. (1880).— "On the Tonicity of the Heart and Blood-Vessels." Joum. of Physiol., vol. 3, p. 53. (1882).—" On the Rhythm of the Heart of the Frog and the Nature of the Action of the Vagus." Phil. Trans. Roy. Soc, vol. 6/, p. 993. BIBLIOGRAPHY 207 Qasser, H. S., and W. J. Meek (1914). — "A Study of the Mechanisms by which Muscular Exercise Produces Acceleration of the Heart." Amer. Journ. of Physiol., vol. 34, p. 48. Gesell, R. (1918). — "Observations on the Volume-Flow of Blood through the Submaxillary Gland." Proc. Amer. Physiol. Soc, p. 545, in Amer. J. Phys., vol. 45. Graham, Q., and E. P. Poulton (1912). — "Influence of High Temperature on Protein Metabolism with Reference to Fever." Quart.. Journ. of Med.,' yo\. 6, p. 82. Qruber, C.' M. (1914). — " The Fatigue Threshold as Affected by Adrenalin and by Increased Arterial Pressure." Amer./. Phys., vol. 33, p. 335. (1917).^ — "Further Studies on the Effect of Adrenalin upon Muscular Fatigue." Amer. J. Phys., vol. 43, p. 530. Haldane, J. S. (1905).— "The Effect of High Air Temperature." Journ. of Hygiene, vol. 5, p. 494. and E. P. Poulton (1908). — " Respiration and Want of Oxygen." Journ. of Physiol., vol. 37, p. 390. and J. Q. Priestley (1905). — "The Regulation of the Lung-ventila- tion." Journ. of Physiol., vol. 32, p. 225. Hamburger, H. J. (1897). — "Einfluss des respiratorischen Gaswechsels auf das Volum und die Form der rothen Blutkorperchen." Zeitschr. f. Biologie, vol. 35, p. 252. Hartrldge, H. (191 2). — " Experiments on the Oxygen Secretion in the Lungs of Man." Journ. of Physiol., vol. 44, p. i. Hasselbalch, K. A. (1912). — " Neutralitatsregulation und Reizbarkeit des Atemzentrums in ihren Wirkungen auf die Kohlensaurespannung des blutes." Biochem. Zeitschr., vol. 46, p. 403. (1916). — "Zur experimentallen physiologie des hohenklimas. V. Die ' reduzierte Ammoniakzahl ' des Hams bei Sauerstoffmangel." Bio- chem. Zeitschr., vol. 74, p. 48. (19 1 7). — " Wasserstoffzahl und Sauerstoffbindung des Blutes." Bio- chem. Zeitschr., vol. 82, p. 282. and J. Lindhard (1911). — " Analyse des hohenklimas in seinen wirk- ungen auf die respiration." Skand. Arch. f. Physiol., vol. 25, p. 361. (191 5)- — "Zur experimentallen physiologie des hohenklimas." Biochem. Zeitschr., vol. 68, pp. 265, 295. (1916). — "Zur experimentallen physiologie des hohenklimas." Biochem. Zeitschr., vol. 74, p. i. and C. Lundsgaard (1912). — " Blutreaktion und Lungen ventilation." Skand. Arch.f. Physiol., vol. 27, p. 13. Hawk, P. B. (1904). — "On the Morphological Changes in the Blood after Muscular Exercise." Amer. Journ. of Physiol., vol. 10, p. 384. Hedvall, B. (1915). — "Fatigue and Training." Skand. Arch. f. Physiol., vol. 32, p. 115. Henderson, L. J. (1908). — "Concerning the Relationship between the Strength of Acids and their Capacity to Preserve Neutrality." Amer. Journ. of Physiol., vol. 21, p. 427. (1909). — " Das Gleichgewicht Zwischen basen under sauren im tieris- chen organismus." Ergeb. Physiol., vol. 8, p. 254. 3o8 THE PHYSIOLOGY OF MUSCULAR EXERCISE Henderson, Y. (1906).— "The Volume Curve of the Ventricles of the Mam- malian Heart and the Significance of this Curve in Respect to the Mechanics of the Heart Beat and the Filling of the Ventricles." Amer. Joum. of Physiol., vol. 16, p. 325. (1909). — " Acapnia and Shock. II. A Principle Underlying the Normal Variations in the Volume of the Blood-stream, and the Deviation from this Principle in Shock." Amer. Joum. Physiol., vol. 21, p. 345. and T. B. Barringer (1913). — "The Conditions Determining the Volume of the Arterial Blood-pressure.". Amer. Joum. Physiol., vol. 31, p. 288. (I9I3)- — "The Relation of Venous Pressure to Cardiac Efficiency." Amer. J. Phys., vol. 31, p. 353. (I9I3)' — "The Influence of Respiration upon the Velocity of the Blood-stream." Amer. Journ. of Physiol., vol. 31, p. 399. and A. L. Prince (1914). — "The Oxygen-pulse and the Systolic Dis- charge." Amer. J. Phys., vol. 35, p. 106. (1914)- — "The Systolic Discharge and the Pericardial Volume." Amer. J. Phys., vol. 35, p. 116. Henriques, V. (1913).— "Ueberdie Verteilung des Blutes vom linken Herzen zwischen dem Herzen und dem iibrigen Organismus." Biochem. Zeitschr., vol. 56, p. 230. Hill, A. V. (191 1). — "The Position Occupied by the Production of Heat in the Chain of Processes Constituting a Muscular Contraction." Joum. of Physiol., vol. 42, p. i. (1912). — "The Heat-production of Surviving Amphibian Muscles during Rest, Activity, and Rigor." Joum. of Physiol., vol. 44, p. 466. — — (1913). — " The Absolute Mechanical Efficiency of the Contraction of an Isolated Muscle." Joum. of Physiol., vol. 46, p. 435. Hill, Leonard (1898). — "Arterial Pressure in Man while Sleeping, Resting, Working, Bathing." Proc. Physiol. Soc. in Joum. of Physiol., vol. 22, p. xxvi. (1909). — "Further Advances in Physiology," p. 112. [Edward Arnold.] and Martin Flack (1910). — "The Influence of Oxygen Inhalations on Muscular Work." Joum. of Physiol., vol. 40, p. 347. — — (1908). — " Respiration." Joum. of Physiol., vol. 37, p. 77. (1909). — "The Influence of Oxygen upon Athletes." Proc. Physiol. Soc. \nJoum. of Physiol., vol. 37, p. xxviii. (1909). — "The Influence of Hot Baths on Pulse Frequency, Blood-pressure, Body Temperature, Breathing Volume, and Alveolar Tensions in Man." Proc. Physiol. Soc. m Journ. of Physiol., vol. 37, p. Ivii. and J. Mackenzie (1909). — "The Effects of Oxygen Inhalation on Muscular Exertion." Proc. Physiol. Soc. m Journ. of Physiol., vol. 39, p. xxxiii. Hlrsch C. (1899). — " Uber die Beziehungen zwischen der Herzmuskel und Korpermusculatur." Deutsch. Arch.f. Klin. Med., vol. 64, p. 597. Hoffmann A. (1902). — "Giebt es eine acute schnell voriibergehende Erweiterung des normalen Herzens ? " Verhandlungen d. Kongress f. innere. Med., vol. 20, p. 307. Hooker, D. R. (1911)- — "The Effects of Exercise upon the Venous Blood- pressure." Amer. Journ. of Physiol., vol. 28, p. 235. BIBLIOGRAPHY 209 Hooker, D. R., D. W. Wilson, and H. Connett (1917).— "The Effect of Carbon Dioxide and Other Substances on the Respiratory and Cardio-vascular Centers." Amer. J. Phys.,\o\. 1^%-^. 2,^1. Hume, W. E. (1918).— " A Study of the Cardiac Disabilities of Soldiers in France." Lancet^ I., p. 529. Hunt {j.?>^f)).—Amer. J. Phys., vol. 2, p. 436. Hyde, J. H., C. B. Root, and H. Curl (1917).— "A Comparison of the Effects of Breakfast, of no Breakfast and of Caffeine on Work in an Athlete and a Non-Athlete." Amer.J. Phys., vol. 43, p. 371. James, William (191 5).— "The Gospel of Relaxation. From Talks to Teachers on Psychology : and to Students on Some of Life's Ideals." Pp. 199-228. Janeway, H. H., and E. M. Ewing (1914).— "The Nature of Shock. Its Relation to Acapnia and to Changes in the Circulation of the Blood and to Exhaustion of the Nerve Centres." Annals of Surgery, vo\. 59. P- 158. Joliannson, J. E. (1893). — "Ueber die Einwirkung der Muskelthatigkeit auf die Athmung und die Herzthatigkeit." Skand. Arch.f. Physiol., vol. 5, p. 20. andd. Koraen (1902). — " Untersuchungen iiberdie Kohlensaureabgabe bei statischer und negativer Muskelth'&tigkeit." Skand. Arch. f. Physiol., vol. 13, p. 229. Joteyko, J. (1904). — "Fatigue." Dictionaire de Physiol., par C. Richet, vol. 6, p. 29. Joseph, D. R., and S. J. Aleltzer (1912).— "The Effect of Stimulation of the Peripheral End of the Splanchnic Nerves upon the Pupil." Amer. /. Phys., vol. 29, Physiol. Proc, p. xxxiv. Katzenstein, Q. (1891). — "Ueber die Einwirkung der Muskelthatigkeit auf den Stoffverbrauch." PflUger's Arch.f. Physiol., vol. 49, p. 379. Kellaway, C. H. (1919). — "Some Physiological Effects of Anoxaemia." Proc. Physiol. Soc, p. Ixiii in/. Phys., vol. 52. Kennaway, E. L. (1908). — "The Effects of Muscular Work upon the Excretion of Endogenous Purines." fourn. of Physiol., vol. 37, p. i. Ikent, A. F. Stanley (1915-1916). — "An Investigation of Industrial Fatigue by Physiological Methods." [ist and 2nd Interim Reports issued from the Home Office.] ICozaWa, S. (1915). — "The Mechanical Regulation of the Heart Beat in the Tortoise." Joum. of Physiol., vol. 49, p. 233. Krogh, A. (1912). — "On the Influence of the Venous Supply upon the Output of the Heart." Skand. Arch.f. Physiol^ vol. 27, p. 126. (1912).— "The Regulation of the Blood Supply to the Right Heart." Skand. Arch.f. Physiol., vol. 27, p. 227. and J. Lindhard (1912). — " Measurements of the Blood-flow through the Lungs of Man." Skand. Arch.f Physiol,, vol. 27, p. 100. (I9I3)- — " The Regulation of Respiration and Circulation during the Initial Stages of Muscular Work." Journ. of Physiol., vol. 47, p. 112. (1917)- — "A Comparison between Voluntary and Electrically Induced Work in Man." Joum. of Pkysiol., vol. 51, p. 182. Krogh, M. (191 5).— "The Diffusion of Gases through the Lungs of Man." Journ. of Physiol., vol. 49, p. 271. 14 2IO THE PHYSIOLOGY OF MUSCULAR EXERCISE Kuno, Yas (191 5).— "The Significance of the Pericardium." Joum. of Physiol., vol. 50, p. I. LAgrange, F. (1889).— " Physiology of Bodily Exercise." (International Scientific Series.) Lamson, P. D. (1915). — "The Role of the Liver in Acute Polycythaemia." J. Exp. Pharm. and Therap., vol. 7, p. 169. Langley, J. N. (191 1). — "The Origin and Course of the Vaso-motor Fibres of the Frog's Foot." Joum. of Physiol., vol. 41, p. 483. Leathes, J. B., and H. Orr (1912). — "The Metabolism of Muscular Ten- sion." Comm. to Physiol. Soc. [vide Bayliss, Principles of General Physiology, p. 543]. Lewis, T. (1908). — "Studies of the Relation between Respiration and Blood- pressure." Part II. Joum. of Physiol., vol. 37, p. 233. (1917). — " Report upon Soldiers Returned as Cases of ' Disordered Action of the Heart ' (D.A.H.), or ' Valvular Disease of the Heart' (V.D.H.)." Special Report Series, No. 8, issued by Medical Research Committee. Cotton, J. Barcroft, T. R. Milroy, D. Dufton, and T. R. Parsons (1916). — " Breathlessness in Soldiers Suffering from Irritable Heart." Brit. Med. Joum., II., p. 516. Lindhard, J. (1912).^— "The Seasonal Periodicity in Respiration." Skand. Arch.f. Physiol., vol. 26, p. 221. (191 3). — " Concerning the Influence of Ultra-violet Light on the Circu- lation in Man." Skafid. Arch.f. Physiol., vol. 30, p. 73. (I9I5)- — " Uber das Minutenvolum des Herzens bei Ruhe und bei Muskelarbeit." Pfluger's Archiv.f. Physiol., vol. 161, p. 233. Loewy, A. (1908). — "Die Gase des Korpers und der Gaswechsel." Oppen- beimer's Handbuch der Biochemie, Bd. IV. (i), p. 10. and H. V. Schrotter (1905). — " Untersuchungen iiber die Blutcircula- tion beim Menschen." Zeitschr.f. Exp. Path. u. Therap., vol. i, p. 197. Lowsley, O. S. (1911). — "The Effects of Various Forms of Exercise on Systolic, Diastolic, and Pulse Pressures, and Pulse Rate." Amer. Joum. of Physiol., vol. 27, p. 446. Macdonald, J. S. (19 14). — "The Mechanical Efficiency of Man." Proc. Phys. Soc. vajoum. of Physiol., vol. 48, p. xxxiii. MacDougall, W. (1908). — " Introduction to Social Psychology," p. 50. [Methuen & Co.] (1908). — "Fatigue." Reports of the British Assot^iation, p. 479. Mackenzie, James (191 3). — " Diseases of the Heart." [H. Frowde.] 3rd edition. Mackenzie, R. Tait (1915).^" Exercise in Education and Medicine." [W. B. Saunders A Co.] 2nd edition. Maitland, T. Q. (1916).— "Accumulated Fatigue in Warfare." Reports of the British Association, p. 253. Mansfeld, Q. (1910). — "Die Ursache der mptorischen Acceleration des Herzens." Pfluger's Archiv.f. Physiol., vol. 134, p. 598. Markoff, 1., F. Miiller, and N. Zuntz (1911).— "Neue Methode zur Bes- timmung der im menschlichen KOrper umlaufenden Blutmenge." Zeitschr.f. Balneologie, vol. 4, pp. 373, 409, 441. BIBLIO GftAPHY 2 1 1 Markwalder, J., and E. H, Starling (1913).— "A Note on some Factors which Determine the Blood-flow through the Coronary Circulation." Journ. of Physiol., vol. 47, p. -275. Martin, E. Q., C. M. Qruber, and T. H. L^nman (1914).— "The Body- temperature and Pulse-rate in Man after Muscular Exercise." Amer. Journ. of Physiol., vol. 35, p. 211. Matliison, Q. C. (191 1). — "The Influence of Acids upon the Reduction of Arterial Blood." Journ. of Physiol., vol. 43, p. 347. (1911). — "The Effects of Asphyxia upon the Medullary Centres.'' Journ. of Physiol., vol. 42, p. 283. Means, J. H., and L. H. Newburgii (1915). — "The Blood-flow in a Patient with Double Aortic and Double Mitral Disease." Journ. of Pharmac. and Exper. Therapeutics, vol. 7, P- 44 '• (191s)- — " The Effect of Caffeine upon the Blood-flow in Normal Human Subjects." Journ. of Pharmac. and Exper. Therapeutics, vol. 7, p. 449- Mettenleiter, M. (1915). — " Untersuchungen iiber den Gaswechsel des tatigen Muskels beim Menschen." Deutsch. Arch. f. Klin. Med., vol. 11 7, p. 517. Miclieil (1909). — AUbutt's System of Medicine, vol. 6, p. 199. Miesclier-Riiscli, F. (1885). — "Bemerkungen zur Lehre von den Athem- bewegungen." Arch.f. Anat. u. Physiol. (Physiol. Abt.), p. 355. Mines, Q. R. (1913). — "On the Summation of Contractions." /. Physiol., vol. 46, p. I. Moore, Benjamin, and F. P. Wiison (1906).— -"A Clinical Method of Haemalkalimetry." Biochem. Journ., vol. i, p. 297. Moritz, F. (1908). — "Uber funktionelle Verkleinerung des Herzens." Munch, med. Wochenschr., vol. 55, p. 713. "Zur Frage von der akuten Dilatation des Herzens durch uberanstrengung." Munch. med. Wochenschr., vol. 55, p. 1331. Mosso, A. (1904). — "Fatigue," transl. by M. and W. B. Drummond. Miiller, Franz (191 3). — "Die Stickoxydulmethode zur Bestimmung des Herzschlagvolumens beim Menschen." Berliner. Klin. Wochenschr., No. 51. '•Myers, C. S* (1918). — "Present-day Applications of Psychology, with Special Reference to Industry, Education, and Nervous Breakdown." [Methuen & Co.] Nicolai, G. F., and N. Zuntz (1914).— "Fullung und Entleerung des Her- zens bei Ruhe und Arbeit." Berliner. Klin. Wochenschr., vol. 51, p. 821. Oliver, Q., and E. A. Sharpey-Schafer (1895).— "Physiological Effects of Extracts of the Suprarenal Capsules." Journ. of Physiol., vol. 18, P- 233- Parnas, J., and Wagner (1914). — " Uber den Kohlenhydratumsatz isolierter Amphibienmuskeln u. uber die Beziehungen Zwischen Kohlenhydrat- schwund und Milchsaurebildung im Muskel." Biochem. Zeitschr., vol. 41, p. 389. Parsons, T. R. (19 17).— "On the Reaction of the Blood in the Body." Journ. of Physiol., vol. 51, p. 440. Patterson, S. W. (1915).—" The Antagonistic Action of Carbon Dioxide and Adrenalin on the Heart." Proc. Roy. Soc, B, vol. 88, p. 371. 14* 212 THE PHYSIOLOGY OF MUSCULAR EXERCISE Patterson, S. W., H. Piper, and E. H. Starling (1914).— "The Regula- tion of the Heart-beat." Joum. of Physiol., vol. 48, p. 465. and E. H. Starling (1913). — "The Carbohydrate Metabolism of the Isolated Heart-lung Preparation." Joum. of Physiol., vol. 47, p. 137. (I9I4)- — " On the Mechanical Factors which Determine the Out- put of the Ventricles." Joum. of Physiol., vol. 48, p. 357. Pembrey, M. S. (1909). — "The Physiology of Muscular Work. Further Advances in Physiology." Pp. 208-257. and R. W. Allen (1905).— "Observations upon Cheyne-Stokes Res- piration." Proc. Physiol. Soc., p. xviii mjourn. of Physiol., vol. 32. C. J. Arkle, P. R. Bolus, and H. C. Lecky (1902).— "The Effect of Muscular Work upon the Temperature of Man." Guy's Hosp. Reports, vol. 57 (52 of the 3rd series), p. 283. and F. Cook {1908). — "Observations upon 'Second Wind'." Proc. Physiol. Soc. xajoum. of Physiol., vol. 37, p. xli. (1908). — "The Influence of Oxygen upon Respiration." Proc. Physiol. Soc. mjourn. of Physiol., vol. 37, p. Ixvii. — — and B. A. Nicol (1898). — "Observations upon the Deep and Surface Temperature of the Human Body." Joum. of Physiol., vol. 23, p. 386. and A. H. Todd (1908). — "The Influence of Exercise upon the Pulse and Blood-pressure." Proc. Physiol. Soc. in Joum. of Physiol., vol. 37, p. Ixvi. Piesch, J. (1909).— "Hamodynamisch. Studien." Zeitschr. f. Exp. Path, u. Therapie, vol. 6, p. 380. , Prausnitz, W. (1892). — "Die Eiweisszersetzung beim Menschen wahrend der ersten Hungertage." Zeitschr. f Biol., vol. 29, p. 151. Rankei (1871). — "Die Blutvertheilung und der Thatigkeitswechsel der Organe." Leipzig, 1871, p. 69. Robertson, O. H., and A. V. Bock (1918).—" Blood Volume after Haemorrhage." Reports of Spedal Investigation Cotamittee on Surgical Shock. No.' 6. Medical Research Committee. Rohde, E., (19 10). — " StofFwechseluntersuchungen am iiberlebenden warm- bluterherzen. i Mitteil : Zur Physiologie des HerzstofTwechsels." Zeitschr. f. Physiol. Chem., vol. 68, p. 181. Roy, C. S., and Graham Brown (1879). — "The Blood-pressure and its Variations in the Arterioles, Capillaries, and Smaller Veins." Joum. of Physiol., vol. 2, p. 323. Rubner, M. (1910). — Sitzungsberichte derpreuss. Akad. der Wissenschaft., vol. 16, p. 316. Ryffel, J. H. (1909). — "Experiments on Lactic Acid Formation in Man." Proc. Physiol. Soc. mjoum, of Physiol., vol. 39, p. xxix. Savage, W. L., and Barasch.— Quoted in Exercise in " Education and Medicine," by R. Tait McKenzie, p. 71. Schneider, E. C, Q. E. Cheley, and D. L. SIsco (1916).— "The Circula- tion of the Body in Man at High Altitudes. III. The Effects of Physical Exertion on the Pulse-rate, Arterial and Venous Pressures." Amer. Joum. Physiol., vol. 40, p. 380. and L. C. Havens (1915).— "Changes in the Blood after Muscular Activity and during Training." Amer. J. Phys., vol. 36, p. 239. (1915).— "Changes in the Content of Hsemoglobin and Red Corpuscles in the Blood of Man at High Altitudes." Amer. J. Phys., vol. 36, p. 380. BIBLIOGRAPHY 213 Schneider, E. C, and D. L. Sisco (1914).— "The Circulation of the Body in Man at High Altitudes : I. The Pulse-rate, Arterial, Capillary and Venous Pressures. II. The Rate of Blood-flow and the Influence of Oxygen on the Pulse-rate and Blood-flow." Amer. J. Phys., vol. 34, p. I. Schott (1908). — "Zur Frage der akuten Herzuberanstrengung." Miin- chener Med. Wochenschr., vol. 55, p. 952. Scott, F. H. (1917). — " Factors Influencing the Interchange of Fluid between Blood and Tissue Spaces. I. Blood-pressure." Amer. J. Phys., vol. 44, P- 298. E. T. Herrmann, and A. M. Snell {1917). — "Factors Influencing the Interchange of Fluid between Blood and Tissue Spaces. II. Muscular Activity." Amer. J. Phys., vol. 44, p. 313. Scott, R. W. (1918).— "The Significance of Undissociated Carbon Dioxide in Respiration." Amer. J. Physiol., vol. 47, p. 43. Sharpey-Schafer, E. A. (191 5).— Quoted by Takayasu, Quart. J. Exp. Physiol., vol. 9, p. 353. Sonne, Carl (1918).— "On the Possibility of Mixing the Air in the Lungs with Foreign Air, especially as it is used in Krogh and Lindhard's Nitrous Oxide Method." Joum. of Physiol., vol. 52, p. 75. Speck (1892). — " Physiologie des Menschlichen Athmens." Leipsic. Spehl ( 1 883). — " De la repartition du sang circulant dans I'dconomie." Thfese, Bruxelles. Starling, E. H. (191 5).— "The Linacre Lecture on the Law of the Heart." Given at Cambridge. [Longmans, Green & Co.] and C. L. Evans (19 14). — "The Respiratory Exchanges of the Heart in the Diabetic Animal." Joum. of Physiol., vol. 49, p. 67. Stewart, Q'. N., and J. M. Rogoff (1916).— "The Influence of Certain" factors, especially Emotional Disturbances,' on the Epinephrin Con^ tent of the Adrenals." Joum. Exper. Med., vol. 24, p. 709. (I9J<6). — "The Spontaneous Liberation of Epinephrin from the Adrenals." Journ. Pharm. and Exfi. Therap., vol. 8, p. 479. (i9i6)- — " Effect of Stimulation of Sensory Nerves upon the Rate of Liberation of Epinephrin from the Adrenals." Journ. Exp. Med., vol. 26, p. 637. (I9I7)- — " Quantitative Experiments on the Liberation of Epine- phrin from the Adrenals after Section of their Nerves, with especial reference to the question whether Epinephrin is essential for the Organism." Proc. Soc. Exp. Biol, and Med., vol. 14, p. 145.1 Tigerstedt, C. (1909). — "Reizung des Ruckenmarkes bei nichtkuraresierten Tieren." Skand. Arch.f. Physiol., vol. 22, p. 142. Vernon, H. M. (1917).— "Output in Relation to Sours of Work. Interim Report of Health of Munition Workers' Committee " [publ. by H.M. Stationery Office]. Verzkr, F. (1912).— "The Gaseous Metabolism of Striated Muscle in Warm- blood Animals." Part I. Joum. of Physiol., vol. 44, p. 243. (1912). — "The Influence of Lack of Oxygen on Tissue Respiration." Journ. of Physiol., \o\. ^^, -p. ■^1). Vincent, Swale, and W. Sheen (1903). — "The Effects of Intravascular Injections of Extracts of Animal Tissues." Journ. of Physiol., vol. 29, p. 242. 214 THE PHYSIOLOGY OF MUSCULAR EXERCISE Weber, E. (1907) " Uber die Ursache derBIutverschiebungim Kdrper bei verschiedenen psychischen Zustanden." Archiv.f. Physiol., p. 300. Willebrand, E. A. von (1903). — "Uber Blutveranderungen durch Mus- kelarbeit." Skand. Arch.f. Physiol., vol. 14, p. 176. Williamson, C. S. (1915).— "The Effects of Exercise on the Normal and Pathological Heart : Based upon the Study of One Hundred Cases." Amer. Journ. of Med. Sciences, vol. 149, p. 492. Winfield, Q. (191 5).— "The Fate of Fatty Acids in the Survival Processes of Muscle." Journ. of Physiol., vol. 49, p. 171. Winterstein, H. (1911). — "Die Regulierung der Atmung durch das Blut." Pfliiger's Archiv., vol. 138, p. 167. Zuntzi H. (1896). — " Ueber die RoUe des Zuckers im thierischen Stoff- wechsel." Archiv.f. Physiol., p. 538. Zuntz, N. (1868).— "BeitragezurPhysiologie des Blutes" (Inaug. Dissert.). Bonn. (1900). — " Ueber die Bedeutung der verschiedenen Nahrstoffe als .Erzeuger der Muskelkraft." Pfliiger's Archiv. f. Physiol., vol. 83, P- 557- (1903). — " Einfluss der Geschwindigkeit, der Korpertemperatur und der Uebung' auf den Stoffverbrauch bei Ruhe und bei Muskelarbeit." Pfliiger's Archiv.f. Physiol., vol. 95, p. 200. (191 1 ). — " Beziehungen zwischen Nahrstoffen und Leistungen des Korpers." Oppenheimer's Handbuch der Biochemie, vol. 4, p. 849. Loewy, Miiller,^ u. Caspar! (1905).— "Hohenklima u. Bergwande- rungen." andlSchumberg (1901). — " Studien zu einer Physiologic des Marsches." Berlin. INDEX. Accelerator tone, 70. Acidosis " compensated," 175. Adrenalin, action of, on capillaries, 95. ■ — on coronary vessels, 112. on skeletal muscle, 128. on the heart, 127. on the pulse-rate, 71. — secretion during anoxaemia, 169. emotional stress, 129. Alkali-reserve, 31, 154. Anticipatory changes in exercise, 116. BAftCROFT-PETERS CUrve, 33, 37. Blood, concentration of, g&, 98. — viscosity of, 96, 98. Buffer salts, 31, 190. — substances, 30. Capillary tone, gi, 95, 122. Coefficient of utilisation, 100. Diffusion-coefficient, 102, 160. Dissociation curve, at high altitudes, 156. during exercise, 103. Efficiency, gross,' 14. — net, IS. — of muscular work, 15. — of the heart, 77, 112. Fatigue, industrial, 180. — of the heart, 178, 199. — sense of, 176. — tests of, 182. H* ion concentration of blood, at high altitudes, 154. — local, 94, 122. Haemoglobin value of blood, at high alti- tudes, 162, 167. — during exercise, 97. — in trained man, 144. Heart, adequate filling of the, 64. — contractile power of the, 55, 67, 75, 194. — diastolic volume of the, 73, 75. — law of the, 54, 120. — nutritive condition of, 76, 195. — size of the, 58, 194. — " soldier's," 29, 188. Induced movements, iig. Lactic acid, significance of, 39. Metabolites, action of, 91. Output of heart, at high altitudes, 158. in trained man, 142, 143. Passive movements, effect of, on pulse- rate, iig. Pericardium, 81. — function of, 56. Pulmonary ventilation, range of, 32. Pulse-rate, at high altitudes, 157. — influence of adrenalin on, 71. reaction of blood on, 72. respiration on, 71. temperature on, 71. — in trained man, 141. — maximal, 76. Respiratory quotient, '6. of heart, 11. Tone of arterioles, 91, 93, 95, 122. capillaries, 91, 95, 122. coronary vessels, 112. the heart, 47, 198. Venous inflow to the heart, 48, 64, 120. — pressure, 66. 21S I^RINTBD IN QRBAT BRITAIN BY THE UNIVERSITY PRESS, ABERDEEN