COLUMBIA LIBRARIES OFFSITE HEALTH SCIENCES STANDARD HX641 35497 111 .H91 The RECAP THE FALL OF THE n: C0LUM9IA {piiifi r-PARTMENfOFtH COULEOE OF PHY^Ct\H9 Ai /,..Ul4>Vbl«'.W i (vXn« r H / ■) NEW YOflK STIMIILATM OF AFFEEEMBfES. a ZhceiQ PRESENTED TO THE BOARD OF UNIVERSITY STUDIES OF THE JOHNS HOPKINS UNIVERSITY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY, BY REID HUNT, A.B. REPRINTED FROM THE JOURNAL OF PHYSIOLOGY, VOL. XVIII 1895. Columbia ©nitJf rsiftp tntlieCitpoflifttjgork CoUege of ^ijpsiicianfi anb burgeons Hibvarp Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons (for the Medical Heritage Library project) http://www.archive.org/details/fallofbloodpressOOhunt THE FALL OF BLOOD-PEESSURE EESETIf FEOM TBE STIMULATION OF AFFERENT NERVES. a ZhCBXQ PRESENTED TO THE BOARD OF UNIVERSITY STUDIES OF THE JOHNS HOPKINS UNIVERSITY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY. BY REID HUNT, A. B. REPRINTED FROM THE JOURNAL OF PHYSIOLOGY, VOL. XVIIL 1895. QPill H9I in [From the Journal of Physiology. Vol. XVIII. Nos. b & > 4 mm. NaOH 1 >> 6 mm. KOH 1-4 )5 10 mm. HNO, 1 )j 10 mm. H„SO. 1 J) 15 mm. Induced current (moderately strong) HCl 1 I Curare was now given and the stimulus applied to the saphenous nerve. NaCl 5 -84 Rise of pressure 1 2 mm. Rise of pressure 7 mm. „ (slight) KCl NaOH KOH NaOH KOH 3-72 1 1-4 1 1-4 14 mm. 11 mm. 8 mm. 11 mm. 10 mm. The vagi were now divided and the stimulus applied to the central end of one of tliese nerves. Induced current (moderately strong) Fall of pressure 8 mm. HNO, 17o Rise „ 24 mm. II. March 28th. Cat, anaesthetized by ether. The experiment was made in the same manner as the ahove. Stimulus % sol. Nerve CaCL 11-1 L. Sciatic Induced current (weak) „ Effect on blood-pressure Rise (very slight) ^ See Griitzner. PJliifjer's Archiv, lviii. 71. 1894. AFFERENT NERVES ON BLOOD-PRESSURE. 395 stimulus 0/0 sol. Nerve Effect on blood-pressure MgSO, 12 L. Sciatic Fall, followed by slight rise MgCl, 16 j> >> J) >} CuiTent (moderate) 5> Rise of 14 mm. BaCl, J> Rise of 7 mm. KC163 12-25 5J Rise, followed by fall HNO3 1 » Fall, followed by rise Current (moderate) )> Rise of 7 mm. Na^SO^ U-0 L. Saphenous Induced current (moderate) >} Rise of 8 mm. ZnSO^ 16-1 >j Rise CuSO^ 15-9 L. Anterior crural '} Fall of 8 mm. Induced current (moderate) KOH l-i Coil Curare was Induced current (strong) NaOH 1 Induced current (weak) KCIO,, 12-25 ,, Rise of 8 mm. ,, Rise of Sh mm. ,, Fall, followed by a rise now given and the vagi cut. R. Vagus Fall of 8 mm. „ Rise of 4 mm. „ Fall of 11 mm. R. Sciatic Rise of 17 mm. „ Rise of 16 mm. followed by fall of 24 mm. These experiments though very incomplete bring out one point of interest, viz., the difference which is sometimes observed between chemical and electrical stimulation. Thus in the first of the above experiments the sciatic readily gave a rise of pressure on stimulation with various chemical agents while electrical stimulation was ineffective; in the second, on the other hand, the latter stimulus was the more effec- tive. A 1 7o solution of HNO3, for example, when applied to the sciatic in the former case, produced a rise of 10 mm., while a moderately strong electrical stimulus was without effect ; in the second experiment, a solution of HNO3 of the same strength, produced a slight fall of pressure, though a weak electrical stimulation was followed by a rise of 7mm. The difference is more marked in the case of the vagi. In both of the above experiments, electrical stimulation of various strengths invariably caused a fall of pressure, while HNO3 and NaOH produced a rise. (See Fig. 3, A and B.) In one case the rise was 24 mm. In an experiment upon a dog a fall of pressure (11 to 12 mm.) followed stimu- lation of the vagus by both the induced current and HNO3 (iVo solution). 306 /?. HUNT. y^^/VvnAr-^ r\. t'^- 'v/^\ ftitltttllttltltlttllttLllllttl /' / I t I » t t t I I I I i t I I I I t I t t t t t I t I I I t I I J \ B Fig. 3. Cat. Ether and Curare. Vagi cut. " A " shows fall of arterial pressure from stimulation of central end of vagus. " B " shows rise of pressure from stimulating vagus with HNO^ (P/o)- Tracing from right to left. So far as these experiments go, I think they show that the effects of both electrical and chemical stimulation vary with the condition of the animal, but that they vary independently. These differences do not seem to be entirely due to differences in the strength of the stimuli. AFFERENT NERVES ON BLOOD-PRESSURE. 397 Path in the cord of the afferent fibres causing a fall of pressure. It seems possible that if the afferent fibres, by which a reflex fall of pressure is brought about, are anatomically distinct from those which cause the usual rise of pressure, that the former may have a separate path in the spinal cord. The pressor fibres from the sciatic were shown by Dittmar^ to run largely in the lateral columns, that is, in the part of the cord in which the nerves giving rise to sensations of pain are supposed to run. It was suggested by Professor Howell that, as the depressor effects were so easily obtained from stimulation of the muscles, the afferent fibres might be those giving rise to the muscular sense. If this supposition is true we should expect section of the posterior columns, in which part of these fibres are known to run, to block, to some extent, depressor influences coming from the sciatic ; and we should further expect stimulation of these columns to produce a fall of pressure. Neither of these suppositions, however, can be con- sidered as satisfactorily demonstrated. In regard to the second point, it may be said that stimulation of the posterior columns gives usually, not a fall, but a slight rise of pressure. The effect of section of the posterior columns upon vaso-motor reflexes is likely to prove, under any circumstances, a difficult problem. For apart from questions of shock, and the fact that many of the fibres of the muscular sense are supposed to run in other parts of the cord, there is clear evidence that a reflex fall of pressure may be obtained through the cord itself at different levels. And, as a matter of fact, some of my experiments show a reflex fall of pressure on stimulation of the sciatic after section of the posterior columns, though this fall was not greater than could be obtained when the entire cord was divided. On the other hand it was noticed several times that after the spinal canal was opened and the posterior columns exposed, a fall of pressure from stimulation of the sciatic was less easily obtained than before. As the posterior columns were the parts most subjected to exposure and injury, this may perhaps be taken to indicate that they are the paths, in part, of the afferent impulses. In any case, it is interesting that after injuries to the cord, pressor effects are usually more marked, while after injuries to the brain the opposite seems to be the usual result. ^ Dittmar. Ber. d. s'dchs. Gesellsch. d. Wiss., Math. phys. CI. 1873, p. 455. PH. XVIII. 27 398 R. HUNT. Part III. On the local action of depressor nerve-fibres, A number of experiments were made to determine, if possible, the vascular area in which the dilatation occurred which was the cause of the fall of arterial pressure described above. It was obviously impossible, from the manner in which these experiments were made, to determine the effect on the vascular area corresponding to the nerves stimulated, for the efferent nerves were cut. However the case may be in the normal animal, it is clear that in these cases the dilatation occurred elsewhere than in the areas supplied by the afferent nerves. It was assumed that the area most probably involved in the dilatation was either the corresponding area of the other side or the splanchnic system, since this is known to play such an important part in most vaso-motor phenomena. Accordingly these two areas were investigated. Method. At first sight the most satisfactory method of inves- tigating this problem seemed to be the plethysraographic. Curare, however, is almost always necessary in such work, and this drug is, as has been shown above, distinctly antagonistic to a reflex fall of pressure from stimulation of sensory nerves. It is obvious, therefore, that the plethysmograph is not applicable to this work and accordingly other methods were tried ; of these the determination of the venous pres- sure in different areas proved the most satisfactory and easiest of application. The method employed was essentially that described by BayTiss and Starling ^ An ordinary Franyois-Franck cannula was used, into the horizontal limb of which a fine pipette was introduced so that it reached just into the neck of the cannula. The vertical limb was connected with a water manometer made of barometer tubing ; a glass T tube was introduced into the rubber tube making this connection. When the vein was clamped, a stream of soda^ could by this arrange- ment be led from the pressure bottle down into the neck of the cannula and out through the vertical limb of the T. The blood in the cannula could thus be washed out and all trouble from clotting avoided. 1 Bayliss and Starling. This Journal, xvi. 162. 1894. 2 The solution of soda used in both the venous and arterial cannulse was the mixtnre of the carbonate and bicarbonate proposed by Klemensiewicz {Sitzber. d, Akad. d. Wiss. z. Wien, Math.-naturw, CI. 94, Abth. 3, pp. 24 — 6, 1886). I have found this solution much more satisfactory than the solutions of MgSO^ and NaXOj commonly employed in the laboratory. The proportions are as follows : Distilled Water 4000 c.c, HNaCOj 186 gm. NajCOj 286 gm. AFFERENT NERVES ON BLOOD-PRESSURE. 399 The veins in which the pressure was determined by this method were the portal, femoral, and saphena. For determining the portal pressure the cannula was introduced into the central end of one of the splenic veins. In the case of the femoral or saphena the cannula was put into a small branch, preferably into one joining the main trunk at a right angle. If a nerve in one leg was to be stimulated, it is to be understood that the cannula was in a vein of the leg of the opposite side. Before describing the results of these experiments a word may be said concerning the interpretation of changes in the portal pressure. So little is known of the action of the constrictors of the portal vein — to what extent and under what circumstances, for example, — they are stimulated reflexly, that one must be very cautious in drawing con- clusions from changes of pressure here. Thus it is conceivable that both the arteries to the viscera and the branches of the portal vein should be constricted or dilated simul- taneously. In this case there would be a rise or fall of arterial pressure with perhaps little or no change in portal pressure. On the other hand a rise of portal pressure might mean a dilatation of the arteries or a constriction of the portal vein and its branches in the liver. A fall of pressure might be ascribed either to a constriction of the arteries or to a dilatation of the veins. Perhaps there may be combinations of these effects. These possibilities show the difficulty of dealing with this subject; still the results are of value when simultaneous records of changes of pressure in other parts of the vascular area are taken. Results. The results of these experiments on venous pressure may be stated very briefly. It was found that in nearly every case a fall of arterial pressure resulting from stimulation of the central end of the sciatic was accompanied by a rise of pressure in the femoral vein of the other leg. In the exceptional cases where no rise was obtained, there was either no change in venous pressure or only a slight fall. This result can not, under the conditions of the experiment, be a passive phenomenon, and I am convinced from a number of obser- vations, that the respiratory reflexes can not be regarded as the cause of it. It seems to be due to an active dilatation of the vessels of the limb.^ The effect on the portal pressure was not so constant, but the result 1 Brunton and Tunnicliff e (loc. cit.) have shown that when a considerable mass of muscle is kneaded there occurs along with the fall of arterial pressure a great increase in the outflow from the veins of the muscles kneaded. 27—2 400 R- HUNT. was usually a fall. Whether this was due to active changes or was merely passive seems at present impossible to determine. Figure 4 shows these results in one experiment. •'vv^vAvvvv^..vvv.'l,/'v^H^'^^'*'^•'^^ FEMORAL I I I I I i I t I t I I I I I i^l I I t ^ I I I I I I t I t t I t t II I I I I ^ —\. Fig. 4. Dog. Ether. Vagi intact. Fall of pressure in carotid and portal vein, and rise in femoral vein on stimulation of sciatic at 10°. All the curve.s have the same base line ; the curves of venous pressure being drawn to indicate the pressure in mm. NaoCOg, the curve of arterial pressure in mm. Hg. The changes of pressure in the curves must be multiplied by 2 to obtain the absolute changes. Tracing from right to left. All three curves are drawn to a common base line. The arterial pressure is expressed in mm. Hg.; the venous in mm. Na^COj solution. To show the absolute changes in pressure the distances of the cupve must be multiplied by two. Both the fall of arterial and the rise of venous (femoral) pressure were slight in this experiment. In some they were 20 and 27 mm. Hg. and 20 and 30 mm. Na^COj respectively, the venous pressure being in such cases almost doubled. Similar effects upon venous pressure were observed when a fall of arterial pressure resulted from cooling and stimulating the ulnar or median. It is interesting to compare with these results the effect on arterial and venous pressure of stimulating the central end of the vagus. This, as is well known, often causes a fall of arterial pressure which has been attributed to an inhibition of the vaso-constrictor centre and a con- sequent dilatation of the arteries, especially those in the visceral area. If this supposition is correct, we should expect to find little or no change in the pressure in the femoral vein, while the dilatation in the splanchnic area might cause a rise of portal pressure. This is, in fact, what was found in a number of experiments (see Figs. 5 and 6). AFFERENT NERVES ON BLOOD-PRESSURE. 401 ^V^'^'^Vv^HvvVvv.vvv^^ CAROTID 4.t«,tilltttllll«lli«lllfllltllitltlll.»i«...)f ......,,...^,,.^^,f 1 L. Fig. 5. Curves similar to above to show changes in portal and carotid pressure from stimulation of central end of vagus. Dog. Morphia and Curare. Tracing from right to left. FEMORAL i I I I I I I I I I I i I 1 I I I i I i « I I I f i i I I i I I I 1 i i I I I i i I Fig. 6. Curves showing changes in pressure in femoral vein and carotid from stimulation of central end of vagus. Dog. Morphia and Curare. The arterial pressure returned from the fall slowly. Tracing from right to left. The rise of portal pressure is often not very marked, but the fact that a large fall of arterial pressure may occur without any change in that of the femoral vein, indicates that the dilatation in such cases is largely elsewhere than in the limbs. It is probably of visceral origin. The fall of arterial pressure is sometimes accompanied by a fall in that of the femoral vein. This is probably a passive effect. Two other experiments indicate that the dilatation occurs elsewhere than in the splanchnic area. The first of these was made upon a dog. The coeliac axis, the renal and the superior mesenteric arteries and the portal vein were ligated ; cophng and stimulating the sciatic continued to cause a fall of pressure. In one case the fall amounted to 28 mm. The aorta was now tied above the inferior mesenteric and the radial stimulated. A fall of pressure was still obtained. In the other experi- 402 R. HUNT. ineut the out-flow from a branch of the femoral vein was measured ; the sciatic of the opposite side was stimulated. In each case the aortic pressure fell on stimulation while the out-flow from the vein was increased. Sometimes the increase was 607o- There seem to have been no changes in respiiation as a result of stimulation. Part IV. General consideration of results. The entire subject of reflex vaso-motor actions is so complex and so little understood, that the explanation of the above experiments is attended with many difficulties. In considering the results of these experiments it will be best to take up, in the first place, the evidence they afford for the existence in ordinary sensory nerves of two sets of afferent fibres to the vaso-motor centre, a set of pressor fibres which cause a reflex rise of blood-pressure, and a set of depressor fibres, stimulation of which leads to a fall of pressure. In the second place, the question as to the manner in which the dilatation leading to a fall of pressure is brought about — whether, for example, it is due to a stimulation of vaso-dilator fibres or to an inhibition of constrictors — may be considered as far as the facts will permit. Is the reflex fall of blood-pressure due to the action of "depressor fibres," or does it depend upon the condition of the vaso-motor centre ? As stated above, the second of these hypotheses seems to have gained most credit with physiologists, and there are many facts whiph indicate that the condition of the centres does modify profoundly the result of stimulating afferent nerves. Thus vaso-motor reflexes obtained from animals in which the cerebral hemispheres are intact differ from those observed when these parts are removed ^ — a fact which is probably explained by the condition of " shock " of the centres in the medulla, resulting from the operation. In the experiments recorded in this paper, however, where the nerve stimulated was subjected to the action of cold, or stimulation was applied to a regenerating nerve, no change can be supposed to have occurred in the centre ; the action in these cases must have been upon the nerve fibres themselves. There are other cases, notably those in which certain anaesthetics or other drugs are used, where it is difficult to determine whether the centres alone are acted upon or whether the nerve fibres are involved. It will be best to consider these various cases separately. 1 See Knoll. Op. cit. p. 456. AFFERENT NERVES ON BLOOD-PRESSURE. 403 1. Methods hy which a reflex fall of blood-pressure can he obtained without any change being produced in the vaso-motor centre. The chief methods are as follows : (1) Stimulation of afferent nerves when cooled, (2) stimulation of regenerating nerves, (3) stimulation of nerves which have been sub- jected to rough treatment or exposure, (4) employment of weak stimu- lation, (5) the mechanical stimulation of muscles. It is apparent at once that in none of these cases can the reflex fall of pressure be attributed to a change in the condition of the vaso-motor centre ; the only part of the reflex arc altered by these agencies is the afferent nerves. As it is difficult to suppose that the same nerve fibres can at one time carry impulses having one effect, and at another impulses having exactly the opposite effect (the condition of the centre remain- ing the same), the simplest explanation of the fall of pressure in the above cases is that there are two sets of afferent fibres ; we may suppose one set to make such connections with the centres that im- pulses passing up it cause a fall of blood-pressure, while the other carries impulses producing a rise. That there are fibres which affect the vaso-motor centre in such a way as to cause a fall of blood-pressure, no one doubts, but they are usually supposed to come entirely from the heart and to run in the special " depressor nerve,'"' or, if this is wanting, in the trunk of the vagus; in the latter case they are mixed with ordinary "pressor" fibres. If the existence of '' depressor " fibres is admitted in this case, it seems much simpler to explain the depressor effects from other afferent nerves in a similar manner. Moreover there is a more or less regular gradation in the effects upon the vaso-motor centre produced by certain nerves. At one end we have the depressor of the heart which, according to most observers, always causes a fall of blood-pressure ; next the vagus of the dog and cat, which causes sometimes a fall, sometimes a rise of pressure, and the glossopharyngeal, which usually gives a fall ; then come such mixed nerves as the sciatic, anterior crural, ulnar, median, the intercostals, and the dog's and rabbit's saphenous, from which depressor effects are obtained usually by special means ; and finally we have the cat's saphenous and the splanchnic, which very rarely under any circum- stances, give a reflex fall of pressure on stimulation. It seems almost necessary to suppose that the fibres of these various nerves make different connections with the vaso-motor centre or centres ; if this is admitted, then we must admit that the fibres are different in the 404 /?. HUNT. sense in which we are using the word, that is, they constitute two diflferent physiological varieties of afferent fibres. The only alternative hypothesis which presents itself would be somewhat as follows. We might suppose one nerve fibre to be con- nected with both a dilator and a constrictor centre ; and perhaps we might further imagine that a weak stimulus could reach or excite one centre more readily than the other, owing to a difference in irritability. In such a case the result of stimulating the afferent fibre would be largely determined by such factors as the strength and nature of the stimulus and the condition of the centres. But such a hypothesis would not explain why, when all the other conditions are the same, a depressor effect is obtained so much more readily from one nerve, e.g. the sciatic, than from another, e.g. the splanchnic. Here again we should have to suppose a difference in the central connections, the fibres of one nerve, for example, making closer connections with one centre than do those from the other nerve. And the same argument would apply with equal force to the difference between the effects of a purely cutaneous and a purely muscular stimulation, the former pro- ducing a rise, the latter a fall of blood-pressure. From these considerations it seems impossible to avoid the conclu- sion that the afferent nerve fibres which cau.se a reflex fall of blood- pressure are anatomically distinct from those which cause a rise of pressure. So far nothing has been said as to the exact manner in which the separation of pressor and depressor effects are produced in the cases where the nerve stimulated has been subjected to cold or exposure, or is regenerating. Granting that there are two sets of afferent fibres making different connections with the vaso-motor centres, we may suppose that a fall of pressure under the above circumstances is produced in one of the following ways. In the first place, we might suppose that the impulses started in both sets of nerve fibres by stimulation are merely weakened by the above influences ; and if it is further supposed that the dilator centre is more irritable than the constrictor centre, then a point might be reached at which the former only was able to respond to the weakened stimulus. It is well known that different medullary centres do differ in their irritability ; the respiratory centre, for example, responds to stimuli too weak to aflfect the vaso-motor centre and, as has been described above, a weak stimulus applied to a nerve often causes a fall of blood-pressure, while a stronger causes a rise. AFFERENT NERVES ON BLOOD-PRESSURE. 405 But there are several facts which indicate that the weakening of the impulses can play but a subordinate part in the cases under discussion. For example, a much greater fall of pressure can be obtained when the nerve is cooled and stimulated, than can be obtained by the use of a weak stimulus alone. Also stimulation of a regenerating nerve may produce, with the fall of blood-pressure, marked respiratory and cardiac reflexes, which indicate that the stimulus could not have been very weak. We are therefore led to the alternative hypothesis as to the mode of action of the above-mentioned agencies in separating the depressor and pressor effect, namely, that when the nerve is cooled or is subjected to exposure, the pressor fibres lose their power of conducting impulses more easily than do the depressor, and that in the case of a regenerating nerve the latter class of fibres grow down or become functional earlier than do the former. This explanation of the action of cold is the one proposed by Howell, who gives also several similar instances of the differential action of cold upon different nerve fibres combined in a common trunk. As regards regenerating nerves, there are already a number of facts which indicate that the fibres in a nerve trunk regenerate, as well as degenerate, at different rates. Thus, as was mentioned above, Howell finds that when the sciatic is cut and the ends sutured together, the vaso-dilators re- generate earlier than do the vaso-constrictors; Ostroumoff ^ showed that the vaso-constrictors degenerate more rapidly than do the vaso-dilators, and Mott ^ has recently stated that there is evidence to show that the afferent fibres in the spinal cord degenerate at different rates after section of a posterior root. 2. Action of ancesthetics and of curare. It is well known that when some anaesthetics, notably chloral and chloroform, are employed, the usual rise of pressure is often replaced by a fall, while when curare is given, a reflex rise is easily and constantly obtained. The exact nature of the action of these drugs has not been deter- mined, but the usual belief is that the drugs affect the nerve centres. This explanation seems very probable, when it is remembered that nerve centres are in general more sensitive to the action of drugs than nerve fibres; and that some of these anesthetics, for example chloroform, cause a fall of pressure, due most probably to a partial paralysis of the vaso-constrictor centre. Still the possibility of a "differential action," 1 Ostroumoff. PJliigefs Archiv, xn. 228. 1876, 2 Mott. Brain, Part i, 1892, p. 2. 406 R. HUNT. to some extent at least, upon the afferent fibres, is not disproved. A few experiments made by applying some of these drugs (chloral, curare, and morphia) directly to the nerve trunk, or by injecting them into it with a hypodermic syringe, gave negative results as far as any change in conductivity or irrita,bility was concerned. But such experiments show little, for the conditions were very different from those which exist when the drug is carried by the blood and the entire length of the nerve is exposed to its action. Ether, applied to the nerve, blocked the afferent impulses, but no separation of pressor and depressor effects was ob- served \ In this connection may be mentioned again the "after-effects" on the blood-pressure of stimulating afferent nerves, especially in animals poisoned by curare or anaesthetised by brain compression. As was described above, the rise of pressure so obtained is often followed by a marked fall. On the hypothesis that in afferent nerves there are two sets of fibres leading to the vaso-motor centre, we may suppose that both are excited simultaneously when the nerve is stimulated, but that the depressor fibres have a long "after-effect"; hence the fall of pressure after the stimulation ceases. This supposition would be similar to the one by which Roy and Adami- explain the vagus effects upon the heai't which occur after the cessation of the stimulation of afferent nerves (the heart being accelerated during stimulation), and to Meltzer's' theory of the after-effects on the respiratory centre from stimulating the central end of the vagus, according to which the in- hibitory fibres exert their influence during, and the inspiratory after,, stimulation. This after-effect on the blood-pressure often occurs only in the eai-ly part of experiments on curarised animals. When the fact is remembered that curare seems to diminish the irritability of the depres- sor mechanism in general (or to increase that of the pressor mechanism, so that when both are thi'own into action the latter predominates), the disappearance of the after-effect may be taken to indicate that this 1 That curare has a marked effect upon the terminations of sensory nerves seems scarcely open to doubt. Heidenhain and Griitzner (PjViyer's Archiv, xvi. 54—56, 1877) showed that often a slight stimulation of the hair of a curarised rabbit produced a much greater rise of blood-pressure than a strong electrical stimulus applied directly to the nerve and, as was shown above, a greater fall of pressure could be obtained by kneading the muscles of a curarised animal than from one simply anaesthetised; in fact a fall of pressure can usually be obtained in this manner from a curarised animal, while cooUng and stimulating the nerve are usually ineffective. - Roy and Adami. Phil. Trans, vol. 183 B, 259. 1892. ' Meltzer. New York Medical Journal, 51, p. 59. 1890. AFFERENT NERVES ON BLOOD-PRESSURE. 407 mechanism is rapidly paralyzed or easily exhausted when this drug is employed. Though it is not definitely proved, the simplest supposition is that the drug acts directly upon the centres ; thus the vaso-dilator centre may be supposed to be affected before the constrictor centre. That the constrictor centre may also be affected is shown by the absence of a reflex rise of pressure after a large dose of curare. What appears to be the opposite effect, viz., a rapid paralysis or exhaustion of the pressor mechanism, is often observed in experiments on etherised animals, especially it seems upon rabbits. In such experi- ments the effect of the first two or three stimulations may be a rise of pressure, after which only a fall can be obtained. The chief factor in diminishing the irritability of the pressor mechanism is doubtless the direct action of the ether upon the constrictor centre, though the possibility of some action upon the afferent nerve fibres can not be excluded. That the latter supposition is possible seems to be shown by the fact that, after one sciatic, for example, has been stimulated till a reflex fall of pressure is obtained (a rise of pressure having followed the stimulations at first), stimulation of the nerve on the opposite side will cause, for a short time, a rise of pressure. This may be taken to indicate a weakening of the power to conduct impulses on the part of the pressor fibres of the nerve, or, on the other hand, to show that when the con- strictor centre is partially paralyzed by the ether, some of its parts are still able to respond, for a time, to impulses coming up the pressor fibres after other parts have been completely exhausted by stimulation. The question which of these suppositions is correct, as well as the entire problem of a differential action of drugs upon the afferent fibres, must be left, for the present, undecided. The nature of the reflex vaso-dUatation resulting from stimulation of the setisory nerves. The data for determining the manner in which reflex vaso-dilatation is brought about, whether by an inhibition of constrictors or by a stimulation of dilators, or by both agencies, are too few to make speculation of much value. But it at least seems very probable, that the mechanism concerned when the fall of pressure results from stimula- tion of ordinary sensory nerves, is different from that called into play in the dilatation resulting from stimulation of the depressor or of the vagus. In the former case the dilatation occurs to a much greater extent in the muscular system, and to a less extent in the splanchnic area, than is the case with the latter nerves. Another point of difference is the effect of curare in the two cases : while this drug usually makes it difiicult or impossible to obtain a fall of pressure from stimulating the sciatic and 408 R. HUNT. similar nerves, it seems to have little or no effect upon the reflex fall from stimulation of the depressor or vagus. Both these points of differ- ence are readily explained, if we assume that the dilatation following stimulation of the depressor or the depressor fibres in the vagus is due to an inhibition of the constrictor centre, while that following stimulation of the sciatic and similar nerves is due to a stimulation of the dilator centre, since in a fall of pressure produced by the latter method we should expect the dilatation to occur chiefly in the muscular system where the dilator fibres predominate, while if the fall of pressure resulted from an inhibition of constrictor fibres we should expect the dilatation to occur mainly in the great splanchnic area where the constrictor fibres predominate. So also the action of curare in the two cases is explained on the above assumption, since it is well known that this drug in the usual doses increases the irritability of the vaso-constrictor centre, and we should therefore expect that it would not prevent the occurrence of a dilatation due to an inhibition of the constrictor fibres as we assume to be the case with the depressor nerve ; whereas curare, according to GaskelP, Eckhard*^ and v. Frey^ diminishes the irritability of the dilator fibres and should therefore tend to destroy or weaken a dilatation due to a reflex stimulation of the dilator fibres as we assume to be the case in the fall of pressure caused by stimulation of the sciatic, etc. The different effects obtained from stimulation of various nerves in animals in which the blood-pressure has fallen as a result of the admini- stration of ether or chloroform, or after exhausting operations, are also more easily explained by this view. Some of my records show that - while the blood-pressure was high, stimulation of the vagus caused a marked fall of pressure, that of the sciatic a rise ; when, however, the pressure had fallen after the administration of ether or the opening of the abdominal cavity, stimulation of the vagus no longer caused a fall of pressure, while there was often a marked fall from stimulation of the sciatic. If we suppose, therefore, that the fall of pressure from stimula- tion of the vagus is due to an inhibition of the constrictor centre and that after etherisation, exhausting operations etc., this effect disappears in consequence of a partial paralysis of the vaso-constrictor centre, the continuance, and indeed augmentation, of the depressor effect upon stimulation of the sciatic under these conditions can scarcely be referred to an inhibition of the constrictor centre, since this is apparently in a 1 Gaskell. This <7ouni«Z, i. 273. 1878— Q. * Eckhard. Beitrage z. Anatomie u. Physiologic, vii. 75. 1876. * V. Frey. Ludwig's Arbeiten, ii. 89. 1876. AFFERENT NERVES ON BLOOD-PRESSURE. 409 condition of depressed irritability. Hence the alternative view, that the fall of pressure is due to a reflex stimulation of the dilator fibres, seems more probable in these cases also\ If we adopt this view it would be better to use the word ' depressor ' in its original sense, i.e. to denote all afferent nerve-fibres producing dilatation by inhibiting the constrictor centre ; and to use some other term, such as "reflex vaso-dilator " (which was employed by Howell), in those cases where the fall of pressure is produced by the stimulation of dilator fibres. Summary of results. (1) A reflex fall of blood-pressure was obtained upon stimulation of the sciatic and other mixed nerves by the following methods. (a) Stimulation of nerves which had been subjected to the action of cold. (b) Stimulation of regenerating nerves. (c) The use of weak stimulation. (d) The mechanical stimulation of nerves ending in muscles. (2) In none of the above cases can the result be attributed to an abnormal condition of the vaso-motor centre. (3) There is very strong evidence for the view that there are "depressor" or "reflex vaso-dilator" fibres in the sciatic and similar nerves. (4) When a mixed nerve is cooled or is subjected to exposure, these fibres retain their power of conductivity longer than do the "pressor" fibres ; when the nerve is cut and sutured, they regenerate earlier than do the latter. (5) Anaesthetics and curare have a marked effect upon the ease with which a reflex fall of pressure is obtained ; ether, chloroform and chloral are favourable, curare unfavourable, to its occurrence. (6) The action of these drugs is probably largely upon the centres ; the above-mentioned ansesthetics probably paralyzing the constrictor, curare the dilator centre. (7) The fall of pressure from stimulation of the sciatic and of simi- lar nerves is of a different nature from that resulting from stimulation of 1 Bayliss (This Journal, xiv. 322. 1893) supposes that the fall of pressure following stimulation of the depressor nerve or the depressor fibres in the vagus is due mainly to a stimulation of the dilator centre, while the similar fall from stimulation of the anterior crural is due mainly to an inhibition of the constrictor centre, but it is difficult to discover in his paper from what evidence he draws this conclusion. 410 R HUNT. the depressor or vagus ; in the former case the dilatation occurs largely in the limbs and curare is distinctly unfavourable to its occurrence ; in the latter case the dilatation occurs to a much less extent in the limbs and curare does not seem to materially affect the ease with which it is obtained. (8) The fall of pressure following upon stimulation of mixed nerves is probably due to a reflex stimulation of dilator fibres. (9) It seems desirable to apply the name " depressor" only to those fibres which inhibit the vaso-constrictor centre and to use " reflex vaso- dilator" for the fibres exciting the vaso-dilator centre. In conclusion I desire to express my sincere thanks to Prof Howell, at whose suggestion this work was undertaken and to whom I am in- debted for much aid and many valuable suggestions. VITA. The author of this thesis was born at Martinsville, Ohio, in April, 1870. He was prepared for college in the public schools of Ohio and in the preparatory department of Wilmington College. After spend- ing a year in the Ohio University, he entered the collegiate depart- ment of the Johns Hopkins University in 1888. He received the degree of A. B. in June, 1891. The year 1891-92 was spent in study, partly in the Johns Hopkins University and partly in the University at Bonn. Returning to the Johns Hopkins, he acted as Assistant in Histology and Physiology 1892-93, and in Physiology 1893-94. In June, 1894, he was appointed Fellow in Physiology and was reap- pointed in June, 1895. COLUMBIA ^^f^:t^::X^ ,„v.de4 W Librarian 1"^,,,.==========^ „^oi_ DA-re^ )RB0V« eo jA-re Ul l^ poe W QPlll H91 Hunt