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 PHYSIOLOGICAL AND PHARMACOLOG- 
 ICAL STUDIES OF THE URETER. III. 
 
 RECAP 
 
 BY 
 
 DANIEL R. LUCAS, M.A., M.D. 
 
 COLUMBIA UNIVFRR'Ty 
 
 DEPARTMENT OF PHYSlPLO^v 
 
 College of Physicians and Surgeons 
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 DISSERTATION 
 
 Submitted in partial fulfilment of the requirements for the Degree of 
 
 Doctor of Philosophy, in the Faculty of Pure Science, 
 
 Columbia University. 
 
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PHYSIOLOGICAL AND PHARMACOLOG- 
 ICAL STUDIES OF THE URETER. III. 
 
 DANIEL R. LUCAS, M.A., M.D. 
 
 DISSERTATION 
 
 Submitted in partial fulfilment of the requirements for the Decree of 
 
 Doctor of Philosophy, in the Faculty of Pure Science, 
 
 Columbia I'ni vcrsity. 
 
 Niav York Citv 
 
 I'M,- 
 

Beprinted from the American Journal of Physiology. 
 Vol. XXII. —July 1, 1908. — No. II. 
 
 PHYSIOLOGICAL AXD PHARMACOLOGICAL STUDIES 
 OF THE URETER. III. 1 
 
 By DANIEL R. LUCAS. 
 
 [From the Laboratory of Biological Chemistry of Columbia University, at the 
 College of Physicians and Surgeons, New Yorh.] 
 
 CONTENTS. 
 
 Page 
 
 I. On transmission of pressure from the bladder to the kidney 245 
 
 II. Ureteral pressure 250 
 
 III. Ureteral pressure and renal circulation 259 
 
 IV. Ureteral pressure and the flow of urine 263 
 
 V. biochemical influences on ureteral pressure 266 
 
 VI. Summary of general conclusions 277 
 
 I. On Transmission of Pressure from the Bladder 
 to the Kidney. 
 
 Introductory. — It is often said that " distention of the bladder 
 seems to cause congestion of the kidneys and, when frequent and 
 long continued, may even be etiological of nephritis." At various 
 times clinicians have asked whether I have noticed regurgitation 
 of urine into the ureter from the bladder. 
 
 Although I have been unable to find any exception to the state- 
 ment that the so-called uretero-vesicular valve is normally quite 
 competent, such questions as the one mentioned above indicate the 
 existence of some doubt as to whether pressure in the bladder may 
 have an effect on the kidneys by direct transmission through the 
 ureter, or only by indirect nervous influence. Publication of some 
 of my notes regarding this matter may therefore be of interest. 
 
 Experimental. — My first observation in this connection was made 
 during an investigation of normal ureteral pressure and its rela- 
 tion to the peristaltic movements of the ureter in the dog. 2 
 
 1 The first paper was published in this journal, 1906, xvii, p. 392; the second 
 t appeared in the New York medical journal, 1907 (August 10). 
 
 2 Lucas: Proceedings of the Society for Experimental Biology and Medicine, 
 
 ],. 6l | also S< i< nee, 1905, xxi, p. 721 ; American medicine, 1905, ix. p. 
 741; Medical news, 1905, Ixxxvii, p. 87. 
 
 245 
 
246 Daniel R. Lucas. 
 
 In that series of experiments a cannula, maintained without liga- 
 tures and not materially interfering with either the flow of urine 
 or the peristalsis of the ureter, was inserted in the ureter at various 
 locations between the kidney and the bladder. It was connected 
 with a water manometer, fitted with float and style to record, on 
 a revolving smoked drum, the intra-ureteral pressure and the effect 
 of the peristaltic waves on that pressure. It was noted that if a 
 kink in, or compression of the ureter below the cannula prevented 
 flow from the ureter, a proportionate increase was registered in 
 the amount of intra-ureteral pressure and the number of peristaltic 
 contractions, — results that confirmed the related conclusions of 
 Sokoloff and Luchsinger. 3 
 
 An unsuccessful attempt was made to cause a more rapid rise 
 in intra-ureteral pressure than was obtainable by the collection 
 above the clamp of urine secreted by the kidney, by squeezing the 
 well-filled bladder with the hand. This was done in a number of 
 animals and frequently repeated in the same animal. In all but 
 one case it was found to be impossible to cause in this way in- 
 creased intra-ureteral pressure. In the one exceptional case the 
 left uretero-vesicular valve seemed to be deficient. The right valve, 
 however, was entirely competent. The force exerted on the bladder 
 in these experiments was sufficient in each case to overcome the 
 compressor-urethra muscle and empty the bladder, or, when the 
 urethra was clamped, to burst the bladder. In the ureter in situ, 
 the animal being narcotized with morphine, the rate of ureteral 
 peristalsis recorded on a smoked drum was, as a rule, increased by 
 the manipulation. This increased contraction was apparently caused 
 by nervous influence and not by mechanical distention (Protocol 
 No. 1). 
 
 The competency of the uretero-vesicular valve was noted in five 
 different experiments in which, also, the ureteral pressure was ob- 
 served as described in Protocol No. 1. The nozzle of a ten-ounce 
 metallic syringe was firmly ligated into the bladder or urethra, and 
 salt solution injected until the bladder burst, without affecting the 
 ureter pressure in any instance (Protocol No. 2). In five perfusion 
 experiments the recording apparatus was not attached, the ureter 
 being merely inspected and palpated. Pressure exerted as described 
 in Protocol No. 2 did not cause dilatation of the ureter. In all 
 
 3 Sokoloff and Luchsinger: Archiv fur die gesammte Physiologie, 1881, 
 xxvi, p. 464. 
 
Studies of the Ureter. 
 
 247 
 
 these experiments the freedom of flow of the perfusion fluid through 
 the kidney vessels was never retarded in the slightest degree by 
 pressure exerted in the bladder (Protocol No. 3). When pressures 
 of 20 to 40 cm. of water were produced in the ureter by injection 
 of Ringer solution through a cannula inserted above the uretero- 
 vesicular valve, the venous flow from the kidney was markedly 
 diminished and the distention of the ureter could be plainly seen 
 and palpated (see Fig. 1). 
 
 FIGURE 1. Upper tracing, drops of fluid from cannula in renal vein. Second tracing from 
 top, time marked in seconds. Third tracing from top, from L cannula in middle por- 
 tion of the ureter. Fourth tracing from top, pressure in renal pelvis registered through 
 a trocar cannula. Straight line, base line for both pressure curves. 
 
 A series of experiments were performed by Dr. Burton-Opitz 
 and myself, in the Physiological Laboratory of the College of 
 Physicians and Surgeons, on the circulation of the blood in the 
 kidneys of dogs anesthetized with ether. We investigated the effect 
 of various pressures exerted at different places in the ureter, and 
 in the bladder, on the rate of blood flow through the kidney, as 
 measured with the Burton-Opitz stromuhr. It was found that the 
 amount of pressure necessary to almost absolutely suppress the 
 flow through the kidney when exerted in the ureter varied directly 
 with the nearness of insertion of the cannula to the pelvis of the 
 kidney. That variation of pressure ranged between 10 to 50 mm. 
 of mercury. 4 
 
 We were unable to note any change in the rate of flow of blood 
 through the kidney in the experiments in which we recorded the 
 
 4 Bi nz and Lucas: Proceeding* of tin- Society for Experimental 
 
 Biology and Medicine, 1908, v, p. 44. 
 
248 Daniel R. Lucas. 
 
 flow from one kidney while special pressure was exerted in the 
 opposite ureter. The results obtained by pressure in the bladder, 
 which was accomplished by compressed air injected at different 
 constant pressures through the urethra, and tried in increasing 
 degrees up to one sufficient to burst the bladder, were also negative. 
 
 In these experiments the animals had previously been subjected to 
 various other tests : to prolonged anesthesia with ether and chlo- 
 roform; their abdominal contents had been exposed and man- 
 ipulated; and often the renal nerves isolated and stimulated by 
 electricity. Consequently a reflex nerve connection between blad- 
 der and kidney or between the two kidneys might easily have been 
 interfered with or destroyed. 
 
 In all experiments in which the flow of blood through a kidney 
 was reduced by pressure in its ureter, the blood flow rapidly re- 
 turned to normal when the pressure was released. 
 
 When the bladder was removed from an animal and water in- 
 jected into it through the urethra until it burst, no leakage was, 
 as a rule, produced through the ureters. 
 
 Conclusions. — The results of these precise experiments accord 
 with the experience of many a boy who has observed that a pig's 
 bladder can be inflated with air by means of a quill inserted in 
 the urethral opening; that such inflation can be made permanent 
 by ligation of the urethra, no attention to the ureters being re- 
 quired; and that the bladder thus distended can be used as a 
 football for days. This shows without doubt that the normal 
 uretero-vesicular valves are entirely competent, and that they wholly 
 prevent the slightest reflux of urine under any degree of pressure 
 which can obtain in the bladder. 
 
 Therefore, as has been suggested above, if a continuous or fre- 
 quently distended bladder has a deleterious effect on the kidney, 
 this effect must be brought about, not by any direct transmission 
 of pressure from the bladder to the kidney, but entirely by a nervous 
 mechanism. 
 
 The latter will be considered more fully in a later research. 
 
 Protocols. 1. Dog; weight, 24.56 kilos. Milk diet for twenty-four 
 hours before the beginning of the experiment. Morphine (6 mg. 
 per kilo) was injected hypodermically at 9.45 a. m., June 23, 1906. 
 11 a. m. Animal profoundly narcotized. A trocar cannula was 
 introduced through the cortex and medulla of the kidney so 
 
Studies of the Ureter. 249 
 
 that it just entered the renal pelvis. The cannula was retained 
 in place by a purse-string suture around the point of puncture of 
 the capsule of the kidney. The urine aspirated fresh from the 
 bladder was injected through the cannula, and the patency of the 
 cannula and the ureter ascertained. An improved T cannula was 
 inserted in the lower third of the ureter. Each cannula was con- 
 nected with a water manometer and the pressure changes were re- 
 corded by means of an Emerson float, 5 on the smoked drum of a 
 kymograph. At first a slightly positive pressure was recorded 
 from the cannula in the straight portion of the ureter, and also 
 from the cannula in the pelvis of the kidney. After a saline 
 infusion of about 400 c.c. in the femoral vein, the amount of 
 secreted urine and the rate of peristalsis were increased, but the 
 intra-ureteral pressure was decreased. The bladder, which was 
 distended with urine, was grasped by the hand, and pressure grad- 
 ually exerted until the sphincter was overcome and the urine re- 
 leased. This Had no effect on the pressure recorded by either 
 manometer, but the irritation of the bladder called forth an in- 
 creased peristalsis. After the urine had escaped, the pressure 
 recorded by the cannulas remained about the same as previously. 
 However, the variations in pressure caused by each peristaltic con- 
 traction were not so great for a time as they had been, but subse- 
 quently the waves resumed the original size. 
 2. Bull dog; weight, 16.8 kilos. Morphine, 0.168 gram at 9.40 a. m., 
 July 3, 1905. Several additional small doses of morphine between 
 10.40 and 11.20. Two cannulas in the ureter of the right kid- 
 ney: one, a trocar cannula through the cortex and medulla of 
 the kidney into the renal pelvis, the other an improved T can- 
 nula, were inserted at the junction of the upper and middle thirds 
 of the ureter. A straight glass cannula was inserted in the left 
 ureter for collecting and measuring the flow of urine. 
 
 As the animal seemed to exhibit special tolerance for morphine, 
 a small amount of chloroform was administered from time to time. 
 A positive pressure of 2 cm. of water was registered from the 
 straight portion at times when the chloroform was used, which 
 caused retardation of the muscular action of the ureter. As the 
 effeel of the chloroform wore off, the pressure in the pelvis of the 
 kidney increased, and the pressure in the straight portion of the 
 ureter fluctuated about a neutral point. One gram of diuretin in 
 30 c.c. of physiological salt solution was infused in the femoral 
 
 ' Emerson: Proceedings of the Society for Experimental Biology and 
 Medicine, [904-1905, ii, p 
 
 Lucas: New York medical journal, August 10, 1907. 
 
250 
 
 Daniel R. Lucas. 
 
 vein. It gave rise to a flow from the left kidney of I c.c. of urine 
 in eight minutes. The tip of a ten-ounce hand syringe was inserted 
 at the urethro-vesicular opening and securely ligated in place. The 
 urethra was clamped, and salt solution was injected into the 
 bladder until the bladder burst. No increase in the pressure in the 
 ureter was shown by the manometer. 
 February 18, 1908. — The kidney, ureter, and bladder of a dog were 
 collectively removed. The cannula and recording instruments were 
 adjusted as described in Protocol No. 2. Ringer solution was per- 
 fused into the renal artery at a constant pressure of 100 cm. The 
 fluid from the renal vein was collected in a graduated cylinder, 
 and record was made of the time which elapsed while 200 c.c. were 
 collected, with the following results : 
 
 Tests applied. 
 
 The urethral outlet was clamped 
 and the bladder was severely squeezed 
 with the hand. 
 
 Ringer solution was injected into 
 the bladder until it burst. 
 
 Note. — The tendency of the vein flow gradually to decrease, as 
 shown by the above figures, cannot be attributed in any degree to 
 the manipulation of or pressure exerted in the bladder. It is a 
 phenomenon observed during the first few hours of all kidney per- 
 fusion experiments, and has been accurately described and charted 
 by Sollmann. 7 
 
 II. Ureteral Pressure. 
 
 Introductory. — The so-called ureteral pressure, which has been the 
 subject of many studies, is, as pointed out by Henderson, 8 a mis- 
 nomer. In the investigations of the so-called ureteral pressure it 
 was not the pressure exerted by the ureter that was studied, but 
 the pressure of the kidney secretion as observed by a manometer 
 tied in the ureter. SokolofT and Luchsinger, Henderson, and others 
 observed that the ureter is capable of contractions sufficiently strong 
 to overcome a very considerable intra-ureteral pressure. They stated 
 that within physiological limits the rate of contraction was directly 
 
 7 Sollmann: This journal, 1905, xiii, p. 249. 
 
 8 Henderson: Journal of physiology, 1905-1906, xxxiii, p. 175. 
 
 Time. 
 
 Fluid from the vein. 
 
 
 
 c.c. 
 
 12.57 p.m. 
 
 
 0.0 
 
 1.11 p.m. (14 min.) 
 
 
 200.0 
 
 1.29 p.m. (IS min.) 
 
 
 200.0 
 
 1.4S p.m. (19 min.) 
 
 
 200.0 
 
 2.09 p.m. (20 min.) 
 
 
 200.0 
 
 2.29 p.m. (20 min.) 
 
 
 200.0 
 
Studies of the Ureter. 251 
 
 proportional to the pressure. I have seen contractions in an iso- 
 lated piece of the middle portion of a ureter from a small dog 
 lift a pressure column of Ringer solution 92 cm. high. I have also 
 recorded graphically contractions under a pressure of 86 cm. of the 
 same solution, which recurred as often as four to five times per 
 minute and, without decreased frequency, for forty minutes, at 
 the end of which time the pressure was diminished. Pharmaco- 
 logical experiments were satisfactorily conducted on this ureter 
 for some time thereafter. 
 
 As I pointed out in a previous paper, 9 the ureteral peristalsis is 
 composed not only of wave motions, due to the shortening of both 
 longitudinal and circular fibres, that travel from kidney to bladder, 
 as described by Engelmann, but also of wave motions in at least 
 that portion of the ureter contained in the renal pelvis, which are 
 distinct and different from the contractions of the straight portion. 
 I believe that further research will justify the general division of 
 the ureter into the following two portions which are distinctly unlike 
 each other in the character of their contractions and functions. 
 
 1. The funnel-shaped portion above the isthmus contained in 
 the renal pelvis and probably partaking of the nerve distribution 
 to the kidney. 
 
 2. The straight portion extending from the isthmus to the 
 bladder, which may be subdivided into (a) an upper third, con- 
 taining nerve endings in its wall; (b) a middle third, deficient in 
 nerve endings; and (c) a lower third, adjacent to the bladder and 
 partaking to some extent of the nerve distribution to the bladder. 
 
 I have often found that the ureter is capable of forcing urine 
 into the bladder, even when sufficient pressure is gradually exerted 
 in the bladder to burst it, no rise of pressure taking place in the 
 ureter either from regurgitation or accumulation of urine secreted 
 by the kidney. 
 
 Various investigations of the so-called ureteral pressure have 
 vn that pressures varying from 5 to 20 cm. of water cause vari- 
 able effects on the amount and constituents of the urine. Thus 
 Steyrer 10 found that pathological closure of one ureter caused an 
 increased flow, diminished specific gravity, and lowered freezing- 
 point of the urine. Pfaundler " observed an increased flow in three 
 
 ' LUCAS : This journal, 1906, xvii, p. 392. 
 
 10 Sti \ Ri r : Beitrggezur chemist hen Physiologie und Pathologie, 1902, ii, p. 312. 
 
 II Pfaundler: lbid. s 1902; ii, \>. 336. 
 
252 Daniel R. Lucas. 
 
 dogs and in one woman under similar circumstances. Schwarz 12 
 noticed that pressures of 10-25 cm. of oil increased the flow of 
 urine, but that greater pressure decreased the flow. Cushny 13 
 found, without exception, that a pressure of 19.5 cm. of water 
 diminished urinary flow in rabbits. Sollmann 14 concluded from his 
 experiments that the cause of the increase is due to forces vital 
 and not mechanical. 
 
 The above-mentioned observations, in the light of my own ex- 
 perience with the ureter, lead me to raise this question : May not 
 the living ureter antagonize transmission of pressure towards the 
 kidney? I believe that definite conclusions on the effect upon the 
 kidney of pressure exerted in the ureter, in situ or uberlebend, are 
 unwarranted before we know definitely how internal pressure in- 
 fluences the ureter. We should know not only the effect in the 
 portion below the isthmus, but also in the portion in the renal pelvis, 
 and the relation of the pressure in these two portions to each other, 
 both normally and when artificially produced. 
 
 Before proceeding to a description and discussion of my experi- 
 ments intended to answer this question, I wish to emphasize one 
 point. In the above statement, uberlebend (i. <?., surviving) is used 
 advisedly. The maintenance for many hours of vital contractile 
 activity in the ureter when excised has made it a very satisfactory 
 subject for the study of many points regarding involuntary muscle 
 tissue. Not long ago I published a tracing showing the effect of 
 caffein on an excised ureter which had been kept in physiological 
 salt solution for five hours after the animal had been killed by 
 pithing. 15 Subsequently, in studies on the ureter and kidney which 
 had been excised jointly and together placed in warm Ringer solu- 
 tion, contraction waves occurred with surprising rapidity and 
 strength during perfusion of the kidneys with Ringer solution 
 twenty-seven hours after their removal from the animal. These 
 waves were graphically recorded. This observation, it will be noted, 
 was made on the second day of the experiment. The temper- 
 ature of the bath had been allowed to fall to that of the room 
 before the end of the first day and the perfusion fluid had been 
 withheld nineteen hours. Moreover, the peristalsis had been en- 
 
 12 Schwarz : Centralblatt fur Physiologie, 1902, xvi, p. 281. 
 
 13 Cushny : Journal of physiology, 1902, xxviii, p. 431. 
 
 14 Sollmann : This journal, 1905, xiii, p. 276. 
 
 15 Lucas : New York medical journal, August 10, 1907. 
 
Studies of the Ureter. 253 
 
 tirely inhibited at the end of the first day's experiment by the use 
 of barium chloride, my intention being to study on the second day 
 the effect of pressure on the dead ureter and kidney as compared 
 with that on the living ureter and kidney on the previous day. Such 
 observations emphasize the vigorous and prolonged vital activity 
 of the excised ureter, — a fact in harmony with similar qualities 
 of the excised kidney, as has been pointed out by Sollmann. 16 
 
 Experimental. Methods. — The present experiments were made on 
 dogs only. As a rule large animals were selected. The ureter was 
 connected with a recording apparatus by 
 
 {A) An improved cannula made of two portions, introduced 
 into the straight segment of the ureter. That part of the cannula 
 between wfeich the vessel wall was clamped was made of half 
 cylinders, the perpendicular cylindrical portions being set nearer 
 one end of each than the other. 
 
 (B) A trocar with a blunt obturator was introduced into the 
 renal pelvis and pushed through the cortex and medulla of the 
 kidney so that it just entered the renal pelvis. 
 
 In the paper on the peristalsis of the ureter two tracings were 
 reproduced for the purpose of illustrating the regularity and per- 
 sistence of ureteral peristalsis. At that time no significance was 
 attached to the fact that, although the tracings were registered by 
 a water manometer, the curve recorded a minimum of 3 mm. and 
 a maximum of 5 mm. positive pressure in the straight portion of 
 the ureter. Throughout the entire period of the three hours that 
 intervened between the two tracings, a constant pressure of 1 1 cm. 
 of urine was maintained at the distal end of the ureter 17 connected 
 with a vertical glass tube from the upper end of which the urine 
 escaped. In that particular experiment the trocar was not intro- 
 duced into the renal pelvis. The observation suggests, however, 
 that there was no transmission of pressure to the kidney through the 
 ureter. 
 
 In fourteen experiments in which the trocar was placed in the 
 renal pelvis an L cannula was inserted at the same time in the 
 straight portion of the ureter at various locations between the 
 isthmus and the bladder, and pressure was exerted in the outlet can- 
 nula 1 I just above the bladder) by one of the following three 
 methods : 
 
 ir ' SOLLMANN : This journal, 1905, xiii, p. 243. 
 
 17 I.u< as : T'li is journal, I'joO, xvii, p. yjj, i a and b. 
 
254 
 
 Daniel R. Lucas. 
 
 {A) The urine was allowed to collect in a vertical tube. 
 
 (B) The outflow was blocked by clamping. 
 
 (C) Fluid was injected through a T cannula, one end of its 
 horizontal arm transmitting the pressure into the ureter, the other 
 to a perpendicular glass tube to which was strapped a metre stick 
 to facilitate the reading of pressure. 
 
 Almost without exception, in the experiments that were conducted 
 without mishap, pressure up to 15 cm. did not cause elevation of 
 the pressure recorded from the straight portion. The pressure in 
 the pelvic portion almost invariably manifested a tendency to de- 
 crease, although under these conditions contraction waves were 
 seldom recorded from the pelvis. When pressure higher than this 
 
 was exerted, a rise of pressure 
 - was frequently recorded from the 
 
 straight portion, the contraction 
 waves becoming often less fre- 
 quent, sometimes more frequent, 
 at which time the tendency to a 
 higher pressure record from the 
 L cannula was less pronounced. 
 Even at this time the trocar, as a 
 rule, recorded zero pressure in the 
 renal pelvis. Nevertheless small, 
 very rapid undulations frequently 
 began to appear on the pelvic 
 tracing (Fig. 2), and if the pres- 
 sure was maintained for a time, 
 or if the ureter was subjected to deleterious conditions such as 
 exposure to cold or desiccation, or if chloroform or any other mus- 
 cular depressant was administered, the pelvic curve showed the 
 tendency to development of a positive pressure, while the straight 
 portion exhibited larger and larger waves, at less frequent intervals, 
 on which smaller waves were often superimposed. 
 
 When, however, the pressure was permitted to continue for a 
 sufficient time or increased, or if deleterious drugs were allowed 
 to influence conditions, a sudden drop of pressure in the straight 
 portion occurred synchronously with an abrupt rise in the pelvic 
 pressure. Both pressures returned quickly to their previous levels, 
 — the ureter pressure by short, step-like ascents, the pelvic pressure 
 by shorter and more rapid descents (Fig. 3). The pelvic pressure 
 
 H- 
 
 -4-4- 
 
 Figure 2. Lower tracing, time in seconds. 
 Second tracing, base line for pressure in 
 the straight portion of the ureter. Third 
 tracing, pressure from the straight por- 
 tion of the ureter. Fourth tracing, pres- 
 sure from the renal pelvis. Fifth tracing, 
 base line for pressure in the renal pelvis. 
 
Studies of the Ureter. 
 
 255 
 
 usually became neutral, the curves often entirely disappearing, the 
 phenomena recurring again and again, tending to become more fre- 
 quent ; but recurrence was by no means regular. Quite often the 
 large ureteral curves were not accompanied by the large pelvic curves. 
 
 fflY^Wl 
 
 ~ M ~~*~~~»*Y^™ M ~' — \r"\r^*~~ 
 
 Figure 4. Continuation of Fig. 3, thirty 
 minutes later. Lower line, base line- 
 Second tracing from bottom, from 
 straight portion of the ureter. Upper 
 tracing, from renal pelvis. 
 
 Figure 3. Lowest tracing, time in seconds 
 and base line for the pressure in the 
 straight portion of the ureter. Second 
 tracing, ureter pressure from straight 
 portion. Third tracing represents the 
 base line for the pressure curve of the 
 renal pelvis. Fourth tracing, pressure 
 from renal pelvis. The more rapid 
 oscillations in the pelvic curve do not 
 show in the figure. 
 
 However, large pelvic curves never appeared under these conditions 
 unaccompanied by decided increase in the size of the ureteral curves, 
 but large pelvic curves could be induced previous to the appearance 
 of, or unaccompanied by, the large curves of the straight portion, 
 by rapidly infusing into a femoral vein 100 to 200 c.c. of warm 
 physiological salt solution. Following the large pelvic curve thus 
 produced, the curves of the straight portion, as a rule, became 
 smaller and more frequent for a time, but subsequently the larger 
 ascents and descents took place again. I am quite sure that the 
 drops in pressure in the straight portion were due to fatigue and 
 relaxation of the ureter; also that the synchronous rises in pres- 
 sure in the pelvic portion, when they occurred, were due to reflux 
 of urine into the renal pelvis, and the return to normal pressure 
 brought about by the recovery and natural peristaltic action of the 
 two portions. 
 
 When, however, the pressure was maintained or increased, or the 
 action of deleterious agents brought to bear on the ureter, the large 
 curve ra\ in the two portions became higher and the period 
 
 of n-turn to their previous levels was more prolonged. Subsequently, 
 if the above-mentioned deleterious influences were continued, the 
 
256 Daniel R. Lucas. 
 
 ureteral curves became more rapid, smaller, and regular. The 
 pressure in the straight portion decreased and the tendency to pro- 
 duction of large curves disappeared. The pelvic pressure increased, 
 however, the curves recording it becoming larger and more regular. 
 These curves from the two portions continued quite regularly for a 
 long time, but occasionally a large ascending curve occurred in the 
 ureteral tracing synchronous with a large descending curve from the 
 pelvic tracing (Fig. 4). This, I believe, was not an evidence of 
 further fatigue, but a manifestation of a tendency to recovery, and 
 illustrates what I think occurs under normal conditions, but which I 
 have been unable to demonstrate with my crude technique, i. e., 
 the tendency of the ureter, by its peristaltic action, to dispel or 
 withdraw from the renal pelvis and kidney all pressure that would 
 tend to arise from the collection of urine in the renal pelvis, per- 
 haps even in the uriniferous tubules. Not infrequently, as before 
 stated, a slight degree of negative pressure was recorded from the 
 renal pelvis at the beginning of different experiments when the 
 ureter w T as contracting actively. Such a negative pressure would 
 explain also why, under my experimental conditions, no pressures 
 could be recorded through the trocar connected with a water 
 manometer, for the exertion of a counter suction caused by the 
 column of water in the manometer would draw the ureter wall 
 against the end of the trocar cannula and thus effectively prevent 
 any variations of pressure from being transmitted. 
 
 It. may be advisable to mention that when membrane tambours 
 were used in place of water manometers, depressions in the pelvic 
 curve were frequently noted to be synchronous with contractions 
 of the straight portion of the ureter, even when fine undulations 
 were not transmitted from the renal pelvis. It seemed, too, that 
 the drop in pelvic pressure coincided closely (when inspected with 
 the naked eye at the time the tracings were being recorded) with 
 the longitudinal motion of the ureter. 
 
 Analysis of some of the experiments on animals successfully used for 
 study in situ of ureteral pressure. — The phenomena produced under 
 these experimental conditions, which appear to be constant and 
 which, I believe, represent closely normal states, are the follow- 
 ing: In four different animals there was a slight degree of nega- 
 tive pressure in the renal pelvis. At that time, in these experiments, 
 the pressure in the straight portion varied from o cm. to 10 cm. 
 of water, positive. In other experiments a negative pressure in 
 
Studies of the Ureter. 257 
 
 the straight portion of the ureter existed to the extent of 4 cm. 
 The difficulty encountered in recording negative pressure from the 
 renal pelvis was also met with in recording the pressure in the 
 straight portion. However, the shape of the cannula may have 
 furnished a condition slightly more favorable; its rigid half- 
 cylindrical walls may have prevented the collapse of the ureter wall 
 against the outlet tube to the manometer. 
 
 In two experiments showing positive pressure in the renal pelvis 
 at the beginning of the experiment (in one, 8 cm., in the other, 
 6 cm. pressure) a kink in one of the tubes was subsequently de- 
 tected which, on removal, allowed the pressure to fall and was 
 without doubt the cause of the high pressure recorded. In four 
 experiments neither negative nor positive pressure was recorded. 
 nor were any contraction waves transmitted until positive pressure 
 was caused by infusion or blocking the outflow of urine. These 
 results demonstrated that the connections and ureter were patent. 
 I am inclined to believe that the above-mentioned neutrality of 
 pressure was due to the fact that the contractions acted so efficiently 
 in carrying the urine away from and past the cannulas that there 
 was lacking the minimal positive pressure necessary for the pro- 
 duction of curves. 
 
 As a rule, increased pressure in the renal pelvis, whether caused 
 by rapid infusion of physiological salt solution into a large vein of 
 the animal, or by injection with a syringe through the wall of the 
 rubber tube connection between the trocar and manometer, promptly 
 increased peristalsis. The latter increased directly as the pressure, 
 shortly afterward regaining the previous frequency and extent. The 
 fact that in the straight portion the peristaltic rate was not so great, 
 even when the pressure in this portion was still rising, after the injec- 
 tion of solution had been discontinued, suggests that the flow of fluid 
 along the ureter under such conditions may also tend to act as a stim- 
 ulus to the contractions aside from that induced by its distention. 
 
 Although as much as 500 c.c. of physiological salt solution was 
 
 infused, in 100 c.c. amounts, at intervals of thirty minutes or less, 
 
 into doj hing about 25 kilos, the ensuing increased flow of 
 
 urine was very marked, but only a temporary rise of pressure in 
 
 renal pelvis and straight portion was noted. There was, of 
 
 irse, an immediate rise of blood pressure. In the renal pelvis 
 
 the pressure increase occurred simultaneously with the infusion. 
 
 earing very shortly after the infusion was stopped. Rise in 
 
258 Daniel R. Lucas. 
 
 the straight portion was somewhat slower, higher, and of longer 
 duration. The usual stimulation of ureteral contractions during 
 the increase of pressure was noted, and it was found that, without 
 exception, the pressure quickly returned to the one recorded previous 
 to the infusion. In fact, the saline infusions, under conditions 
 where the resistance to the outflow was not too great, seemed to 
 favor peristalsis more decidedly and to cause a diminution of intra- 
 ureteral pressure. 
 
 Conclusions. — I believe these experiments indicate very strongly 
 that under normal conditions the intra-ureteral pressure remains at 
 zero. The amount of urine in the ureter that ordinarily is necessary 
 to call forth peristalsis is probably so slight that it causes scarcely 
 any pressure in the relaxed ureter, and in the case of normal per- 
 istalic contraction directs the urine into the bladder. At the same 
 time a tendency to the production of negative pressure is doubtless 
 exerted behind the mass of urine that proceeds downward. The 
 flaccid muscular walls would be collapsed by such a negative intra- 
 ureteral pressure, however. A mechanism by which negative pres- 
 sure could be attained to an appreciable degree in the straight 
 portion is difficult to conceive. In the renal pelvis conditions are 
 somewhat different. In the first place the shape of the ureter above 
 the isthmus becomes more and more flared. This portion is held open 
 by its attachment to the firm kidney substance. Again this portion 
 is abundantly supplied with nerves. From my observations of the 
 action of this portion of the ureter, I am inclined to believe that 
 here conditions prevail which are less favorable to accumulation of 
 urine and more favorable to a negative pressure. However, there 
 are other phenomena than those already mentioned that indicate 
 highly co-ordinated and purposeful actions of this portion. 
 
 From the above observations, based as they are on experimental 
 study, it appears that the ureter is specially antagonistic to trans- 
 mission of pressure towards the kidney. The portion of the ureter 
 above the middle, unenervated third, is apparently even more 
 efficient in its resistance than the lower portions. The pressure 
 necessary to overcpme this action, under the above-mentioned con- 
 ditions of experimentation, is somewhat above that produced by a 
 30 cm. column of water, and varies naturally with the duration of 
 application, drugs used, exposure, size of animal, etc. 
 
Studies of the Ureter. 259 
 
 III. Ureteral Pressure and Renal Circulation. 
 
 Introductory. — The experimental results already recorded here 
 indicate that the ureter is more than a simple conducting" tube. It 
 not only carries urine away from the kidney and discharges it into 
 the bladder, but by its peristalsis it also prevents collection of urine 
 in the renal pelvis, thus inducing a condition favorable to continuous 
 flow from the tubules and spaces of Bowman's capsules. This state 
 of affairs brings to mind a much studied problem, namely, the 
 nature of urinary secretion. 
 
 The physical phenomena in the secretion of urine have recently 
 been extensively studied by Sollmann, 18 who states with accuracy, 
 " a knowledge of the mechanical phenomena occurring in the kidney 
 would seem to be a necessary prerequisite to the discussion of any 
 theory of urine secretion." 
 
 It is obvious that any influence the ureter may exert on the kidney 
 must be primarily mechanical. Therefore I have made a study of 
 certain mechanical phenomena in urinary formation, with the ureter 
 and the glomeruli of the kidney especially in mind as influencing 
 factors. 
 
 Experimental. Methods. — In these investigations I have followed 
 in a general way Sollmann's technique for perfusing excised kid- 
 neys. I am indebted to Professor Sollmann for important sugges- 
 tions in this connection. My experiments differ chiefly from his 
 in that most of his work was done on kidneys in which the vital 
 action was very largely excluded and the action of the ureter given 
 little attention, while I have tried to control the mechanical phe- 
 nomena to as large a degree as possible by removing the kidney 
 and ureter from the animal, at the same time endeavoring to main- 
 tain the vital action of the ureter. 
 
 I have also performed a number of perfusion experiments by 
 Sollman's technique exactly, in order to test his methods. Finding 
 that my results confirmed his observations and conclusions, I based 
 many of my tests and observations on his analogous data. 
 
 The vitality of the kidney and ureter is very persistent. — 
 
 Sollmann presented evidence showing that a certain degree of 
 
 vitality is maintained by the excised kidney for many hours. His 
 
 icriments and conclusions applied to both the vitality of the se- 
 
 1 * Sollmann: This journal, 1905, xiii, p. 241. 
 
260 Daniel R. Lucas. 
 
 cretory epithelium and the blood vessels. His results for the vessels 
 are classified under the heads : ( i ) Dilator reaction ; (2) Adrenalin 
 reaction; (3) Hydrocyanic acid reaction. Sollmann's experimental 
 results show that the vessels maintain vital activity to some degree 
 two days after excision. 
 
 As I stated before, my attention has been directed in this research 
 to the vascular system of the kidney and to the ureter. I have con- 
 firmed the results of Sollmann on the vessels, and have investigated, 
 in addition, the effects of the following on the ureter and on the 
 vessels of the kidney: adrenalin, barium chloride, caffein, diuretin, 
 chloral, chloroform, magnesium sulphate, physostigmin, atropin, 
 pilocarpin, cocain, sodium chloride, oxygen, carbon dioxide, cerium 
 nitrate, heat, cold, mechanical irritation and electricity. 
 
 My observations of the effects of the above-named substances and 
 conditions will be taken up in detail in the fifth section of this paper. 
 It is sufficient to state here that the vessels of the excised kidney 
 and the ureter are susceptible to the influence of drugs for many 
 hours after excision. 
 
 In the living animal there are many conditions that influence the 
 renal circulation. The following technique was used to eliminate 
 such undesirable influences as changes in general blood pressure and 
 nervous control. 
 
 The animal was anesthetized with ether or the skin over the 
 femoral artery cocainized, the artery exposed and cannulized, and 
 the animal bled to death. An incision was then made along the 
 linea alba from ensiform cartilage to symphesis pubis and, by trans- 
 verse cuts, extended from the first wound through the abdominal 
 muscles to the dorsal region, passing just below the last rib. The 
 ureter, kidne)^, and bladder were exposed by retracting the other 
 abdominal viscera in warm towels. The artery of the kidney to 
 be studied was exposed and cannulized with as large a glass cannula 
 as could easily be inserted. This was filled immediately with warm 
 Ringer solution, and, by means of a ten-ounce hand syringe joined 
 to the cannula by a short piece of rubber tubing, the kidney vessels 
 were flushed with Ringer solution at 38 C. until the vein flow 
 was seen to be clear. The vein was then cannulized. A trocar 
 cannula was introduced and retained in the renal pelvis, and an L 
 cannula inserted into the straight portion of the ureter. If the 
 ureteral flow was to be noted or the effect of injection into it studied, 
 a small straight glass cannula was inserted just above the bladder 
 
Studies of the Ureter. 261 
 
 and the ureter severed below the cannula. The kidney and adjacent 
 vessels and cannulas, with the ureter, were removed to a bath of 
 Ringer solution maintained at a constant temperature of 38 ° C. ; the 
 artery was connected to a perfusion apparatus consisting of a 20-litre 
 bottle, filled with Ringer solution and fitted with a Mariotte tube for 
 maintaining constant pressure, and elevated to such a height that 
 an injection pressure of 122.5 cm. was constantly maintained. A 
 litre flask was inserted in the system and placed in a water bath, 
 by means of which the temperature of the injection fluid could be 
 kept constant. A thermometer inserted through the vertical arm 
 of a T tube just proximal to the point of injection indicated the 
 temperature of the perfusing fluid at its entrance to the artery, 
 which temperature was maintained at 38 C. The cannula in the 
 straight portion of the ureter and the one in the renal pelvis were 
 each connected to a membrane tambour. This tambour was adjusted 
 to write on the revolving smoked drum of a kymograph on which 
 the time was marked in seconds, and the rate of vein flow recorded 
 in drops from the vein cannula allowed to fall on the paddle of a 
 Marey tambour. The outlet cannula of the ureter was connected 
 by means of a T tube to a perpendicular tube by which the rate 
 of flow or the resistance of flow to artificial pressure could be varied 
 at will. 
 
 Results The fifth experiment being representative, it will be 
 
 used as illustrative of the phenomena thus far observed by this 
 method. In this experiment the outlet cannula of the ureter was 
 connected with the perpendicular tube for the purpose of causing 
 automatic increase of pressure at the distal end of the ureter. 
 
 5. February 18, 1908. — On opening the arterial clamp the kidney be- 
 qame tense, the vein flow started immediately and was very free 
 — twelve drops per second. The pressure in the renal pelvis rose 
 abruptly as the injection fluid entered the kidney. The pressure 
 was slight and showed no tendency to change for several hours. 
 No contraction curves were registered from this portion of the 
 ureter until later, when the straight portion was overcome by pres- 
 sure and fatigue. 
 
 The pressure in the straight portion of die ureter remained at 
 zero for ten minutes, no peristaltic waves being recorded. At the 
 
 d of that time a very slight rise in the intra-ureteral pressure of 
 the straight portion was noted, when the peristaltic waves began 
 abruptly and continued at the rate 01 one ill ten seconds, tending 
 
262 Daniel R. Lucas. 
 
 to increase in rate as the pressure rose, until the pressure reached 
 18 cm., when the curves became larger and slower. 
 
 After the rapid primary flow from the vein had reached its 
 maximum there was a gradual decrease as the time of perfusion 
 advanced. In what Sollmann 19 describes as the third stage in per- 
 fusion of the excised kidney, at the point where the vein flow re- 
 mains almost constant (Fig. 5), there was a tendency at times 
 when the ureter action was most efficient, toward an increase in the 
 vein flow (Fig. 6). 
 
 4^%llW^ 
 
 111« 1 11^MJ1UU1)UB111MW1BU 1 WPWW- 
 
 Figure 5. Upper tracing, vein flow in drops. Second trac- 
 ing from top, time in seconds. Third tracing from top, 
 ureteral pressure through the cannula in the middle of 
 the straight portion. Fourth tracing from top, pressure 
 from renal pelvis. Lowest tracing, base line for both 
 pressure curves. The tracings were recorded two hours 
 and ten minutes after perfusion was started. The num- 
 ber of ureteral contractions during the last thirty minutes 
 of this time averaged 56.1 per ten minutes ; the vein flow 
 per ten minutes, 2056.8 drops (124.4 c.c). 
 
 Figure 6. Same as Fig. 5, 
 obtained twenty minutes 
 later, the resistance to the 
 ureteral outflow having 
 been increased in the 
 meantime from 5 to 10 
 cm. of water. Ureteral 
 contractions averaged 109 
 per ten minutes. Vein 
 flow, 3840 drops (228.5 
 c.c.) in the same time. 
 
 When relaxation and inactivity of the ureter took place, there 
 was a marked decrease of the pressure in the straight portion of 
 the ureter which was transmitted to the pelvic portion ; at the same 
 time the vein flow was abruptly reduced from 10 to less than 1 
 drop per second (Fig. 7). When the intra-ureteral pressure was' 
 rapidly increased by injection of Ringer solution through the out- 
 let cannula, the primary effect of the increasing pressure in the 
 renal pelvis was an increased vein flow (probably due to expres- 
 sion from the renal vessels). The vein flow then steadily decreased 
 as the pressure increased. When a maximum pressure of 38 cm. 
 
 19 Sollmann: This journal, 1905, xiii, p. 249, Fig. 2. 
 
Studies of the Ureter. 263 
 
 was caused in a period of twelve seconds, the above-described 
 phenomena were noted in spite of the maintenance of this maxi- 
 mum pressure, and the vein flow again tended to increase rapidly, 
 but in the succeeding ten minutes did not attain the rate noted 
 previously to the inauguration of the pressure (Fig. 8). Again, 
 if the above-mentioned pressure was obtained by six separate in- 
 jections at intervals of ten to fifteen seconds, the retardation of the 
 vein flow was much less distinct. 
 
 IV. Ureteral Pressure and the Flow of Urine. 
 
 Introductory. — The results of many of my experiments have led 
 to the conclusion that the ureter acts in an antagonistic manner to 
 pressures toward the kidney, and that this action of the ureter not 
 only protects the kidney from pressure caused by accumulation of 
 urine in the renal pelvis, but also encourages the flow of blood 
 throughout the kidney. 
 
 Inasmuch as the ureter influences by its action or non-action the 
 flow of blood throughout the kidney, the ureter must, to that extent 
 at least, influence the flow of urine. In some of my experiments 
 I observed that, in the excised ureter and kidney, the ordinary re- 
 lation between them was somewhat different from any noted when 
 in situ. The present study has been carried out on the kidney and 
 ureter in their normal relationships in order to determine more 
 intimately, if possible, the ureteral influence on urinary flow. 
 
 Methods. — The animal was kept on a soft or liquid diet for 
 several days, then narcotized by hypodermic injection of morphine, 
 placed in a dog-holder, 20 'and shaved dorsally from the last rib to 
 the crest of the ileum on each side. An incision was made 'from 
 the angle between the last rib and vertebral column, extended down 
 and outward, and the ureter in its middle or lower third was ex- 
 posed retroperitoneally. A small glass cannula was introduced into 
 the ureter, which was severed below the cannula and brought to 
 the edge of the wound, the wound closed by interrupted sutures, 
 and the ureter fixed by attaching it, by a slight stitch in its wall, 
 to the surrounding muscle. The urine from each ureter was caught 
 in a 100 c.c. graduated cylinder and saved for examination. The 
 normal' rate of flow from each kidney was recorded. When this 
 bad been satisfactorily determined, one of the ureteral cannulas 
 20 Meyer: This journal, 1907, xxix, p. 906. 
 
264 Daniel R. Lucas. 
 
 was joined to a perpendicular glass tube of small calibre by the 
 side of which a metre stick was fastened. The other cannula was 
 not interfered with, nor was the ureter disturbed by the adjustment 
 of connections. Thus the effect on the ureter and kidney of gradu- 
 ally increasing pressure caused by the secretory activity of a kidney, 
 as well as the continuance of flow from each kidney, was observed. 
 
 Deductions regarding transmission of ureteral pressure to the 
 kidney were made (a) from the aspect of the undulations brought 
 about by the contractions of the ureter caused in the vertical tube 
 
 Ui^uaniUJJliyUii^j_U_L 
 
 Figure 7. . Figure 8. 
 
 Figure 7. Same as Fig. 5, four hours after Figure 8. Same as Fig. 7 (later). Peri- 
 perfusion was started. Peristalsis infre- stalsis having ceased, ureteral pressure 
 quent and irregular, ureter relaxing at rapidly increased to 38 cm. (of water), 
 times, allowing pressure to be transmitted 
 to the renal pelvis. Vein flow averaged 
 1510 drops (94.25 c.c.) per ten minutes. 
 
 through which the pressure was exerted; (b) from changes in the 
 amount and composition of the urine, and (c) from the results of 
 post mortem examination of the kidney. 
 
 The cannulas were maintained in the ureters two or three days, 
 at the end of which time they ceased to remain in place, because 
 of pressure necrosis of the ureter due to the retaining ligature at 
 the point of insertion into the ureter. The animal was continuously 
 protected from pain by small though sufficient doses of morphine. 
 Readings were made on each day for periods of three to five hours. 
 
 Inasmuch as the results obtained on the first days of Experiment 
 No. 2 are typical, they will be cited by way of illustration. 
 
 Results. — The curves of Fig. 9 show two distinct effects of pres- 
 sure on the rate of flow, i. e., a decided increase between pressures 
 of 2.5 and 25 cm., and a decrease commencing as the pressure rose 
 above the 25 cm. mark. At the time of experimentation it was 
 noted that while the flow was increased as the pressure rose in the 
 perpendicular tube towards the 25 cm. mark, the meniscus rose and 
 fell in a rapid and regular manner, which fluctuations, 'had the 
 
Studies of the Ureter. 265 
 
 pressure been recorded by the graphic method, would have given a 
 curve of the character shown in Fig. 2 (third tracing from the 
 bottom). I believe the intra-ureteral pressure conditions repre- 
 sented by the figure referred to are entirely analogous to those 
 attained by the above-mentioned method, i. e., the pressure exerted 
 at the ureteral outlet is not transmitted to the renal pelvis, there- 
 fore does not act on the kidney, as such, although the stimulation 
 of the ureter may have an indirect effect on the kidney. 
 
 When the column of urine nearly reached the 25 cm. mark, the 
 oscillations became greater in extent and irregular in rate. The 
 same pressure also caused retardation of the flow of the urine. The 
 oscillations of pressure, if recorded at that time, would have exhib- 
 ited a curve of the type shown in Fig. 3 (second tracing from the 
 bottom). The oscillations indicated, I think, the time at which the 
 ureter muscle was succumbing to the pressure and fatigue. At that 
 point, for the first time, pressure as such exerted at the outlet of the 
 ureter was transmitted through the ureter to the kidney. I do not 
 believe that even at that time the pressure was transmitted in its 
 entirety. Furthermore, its action was probably only for brief 
 periods. 
 
 The column of urine continued to rise and oscillate in the above- 
 mentioned manner until, after a time, the pressure approached 
 50 cm., when again the type of oscillation of the column of urine 
 gradually changed to that represented by the curve in Fig-. 4. This 
 curve is characterized by the sudden falls of pressure and the more 
 gradual returns to the previous levels, by very small and rapid os- 
 cillations, as shown by the second curve from the bottom of Fig. 4. 
 
 As the pressure increased from 50 to 67 cm. the fluctuations be- 
 came smaller, being of the type shown on the ascending portion 
 of the curve in Fig. 3. As the pressure gradually rose during this 
 period, fluctuations of greater extent occasionally appeared, as is 
 shown in Fig. 4. 
 
 After the column of urine reached the 65 cm. mark, there was 
 no fuvther ascent during the remaining thirty-six minutes of ob- 
 servation, the oscillations in the pressure tube also disappearing. 
 
 Without exception, in these experiments slight pressure, i. c, 
 from 2.5 t<> 25 cm., was accompanied by increased How of urine 
 from the ureter in which the pressure was exerted. The results 
 of pr< xperimenta on the ureter, compared with the oscilla- 
 
 tions of the fluid in the pressure tube in these experiments, make 
 
266 
 
 Daniel R. Lucas. 
 
 me certain that pressures exerted in the ureter between 2.5 and 
 25 cm. were not transmitted as such to the renal pelvis. It is 
 probable, however, that pressure between 25 and 50 cm. may have 
 been transmitted to a slight degree at moments of relaxation of the 
 ureter, when the abrupt drops in the column were noticeable. 
 
 The behavior of the ureter, when the pressures varied between 
 the 50 and 67 cm. marks, suggests that its resistance was overcome, 
 and that such pressures were transmitted almost entirely to the 
 kidney, under which condition there was absolute stoppage of the 
 urine flow from that kidney during a period of eighteen minutes. 
 
 The animal was then returned to its cage at 4.30 p. m. (October 
 12, 1907), and given food and water (500 c.c). 
 
 The curve plotted from the rate of ascent of the urine secreted 
 in the vertical tube is shown in Fig. 9. 
 
 The total amount of urine excreted between 4.30 p. m. (October 
 12, 1907) and 9 a. m. (October 13, 1907) was 175 c.c, at which 
 time the animal was given 500 c.c. of water. At 10 a. m., 0.044 §" m - 
 of morphine were injected hypodermically. At 10.45 A - M -> 35° c - c - 
 of clear material was vomited. When the animal became thoroughly 
 narcotized, it was again placed in the dog-holder, and at twelve 
 o'clock the collection of urine was begun. The urine from the leffe 
 kidney was clear and reddish, while that secreted by the right 
 kidney was clear and yellowish. 
 
 The rate of flow from each kidney was recorded as follows : 
 
 rime of observation. 
 
 Urine from 
 right kidney. 
 
 Urine from 
 • left kidney. 
 
 
 
 c.c. 
 
 
 c.c. 
 
 First 30 minutes 
 
 
 6.20 
 
 
 6.15 
 
 Second 30 minutes 
 
 
 4.80 
 
 
 4.85 
 
 Third 30 minutes 
 
 
 4.00 
 
 
 4.00 
 
 Fourth 30 minutes 
 
 
 2.90 
 
 
 
 Fifth 30 minutes 
 
 
 2.20 
 
 
 3.50 
 
 
 No 
 
 albumin. 
 
 Albumin present, 
 
 
 Sp. 
 
 gr. 1 0245 
 
 Sp. 
 
 gr. 1.0277 
 
 Remarks. 
 
 The urine was allowed to 
 flow from the ureteral can- 
 nulas without resistance. 
 
 The ureter from the left 
 kidney was attached to a ver- 
 tical tube ; the right, as above. 
 
 V. Biochemical Influences on Ureteral Pressure. 21 
 
 The ureter is a highly specialized, involuntary muscular organ, 
 and has been the fruitful subject for many investigations of the 
 myogenic and neurogenic origin of automatic muscular contractions. 
 
 21 Some of the experiments of this section were performed in the Department of 
 Pharmacology in this institution under the direction of Dr. A. N. Richards, to 
 whom I am indebted for much assistance. 
 
Studies of the Ureter. 
 
 267 
 
 The conclusions of such studies of the ureter have often been ap- 
 plied to the beating of the heart and to the movements of the in- 
 testines and other organs largely made up of smooth muscle fibres. 
 However, the extent of the nerve supply of the middle portion of 
 the ureter is a debatable question (Englemann, Dogiel, and others). 
 Protopow made an extended study of the separate existence of the 
 requisite elements for muscular contractions. 22 He used the ureter 
 as the subject of his investigations, which were both histological and 
 biochemical in nature. He concluded that the requisite elements for 
 muscular movements are found separately in the ureter of man and 
 the higher animals. He also stated that stimulating the splanchnic 
 
 X 
 
 1 
 
 i 
 
 
 
 
 
 
 I 
 
 
 
 
 
 . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 -1 
 
 
 
 
 
 
 
 
 
 « 
 
 
 
 ^ 
 
 
 
 
 
 
 
 
 
 u 
 
 -8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Figure 9. The curve is constructed from the records of the time required for the ex- 
 creted urine to make successively an advance of one inch in the vertical tube ; increas- 
 ing pressure is automatically exerted by the rising column. 
 
 nerves has a motor effect on the ureter. Fagge 23 pointed out that 
 stimulation of the hypogastric nerve has a motor effect on the por- 
 tion of the ureter adjacent to the bladder. 
 
 Of more purely biochemical nature are the researches of Stern, 24 
 Hedon and Fleig, 25 Manevitch, 26 Pugliese, 27 and others, in which 
 the control of automatic movements of the ureter by various cations 
 and anions has been extensively studied. Hedon and Fleig in- 
 vestigated especially the effects of the ions which are found in the 
 various artificial blood sera. 
 
 " PROTOPOW: Archiv fiir die gesammte Physiologie, 1897, lxvi, p. 1. 
 
 23 FAGGE : Journal of physiology, 1902, xxviii, p. 304. 
 
 24 STERN : These de (Geneva, 1903. 
 
 26 HEDON et FLEIG : Archivea internationales de physiologic, 1905-1906, iii, 
 
 P. <r 
 
 '» Manevitch : Revue metlicale de la suisse romande, 1907, ncvii, p. 585. 
 ' n Pugliese: An hives Italiennea de biologie, 1906-1907, xliii, p. 54. 
 
268 Daniel R. Lucas. 
 
 Manevitch divides the cations which affect the contractions of 
 the ureter into three groups: (i) Those which have the power of 
 preserving to the highest degree the automatic contractions of the 
 excised ureter (smooth muscle tissue), e. g., Na and Li; (2) Those 
 which depress the tonus and stop the rhythmic and automatic func- 
 tion of smooth muscle, K, NH 4 , Mg, Zn, Cd, Pb, Co, Ni, Fe, Mn, 
 Cu; (3) Those which are stimulants to the tonus, and aid develop- 
 ment of the rhythmic and automatic action of smooth muscle, fore- 
 most among which are Ba and Sr. Ca, according to Manevitch, 
 occupies a special place, having some of the characters of barium 
 and strontium. It causes a development of deficient automatic con- 
 tractions, and renders better, and more energetic, the contractions al- 
 ready in progress, but, on the other hand, often tends to inhibit or 
 retard the rhythm. 
 
 The cations Sr and Ba are conceded by Manevitch to be antago- 
 nistic, in their action on smooth muscle tissue, to those of the second 
 group named above, i. e., to K, NH 4 , Mg, etc. Manevitch also states 
 that when the automatic contractions of the ureter have become 
 greatly diminished after hours of rction in solutions containing in- 
 different cations such as Na, Li, CI, they are again greatly revived 
 by solutions containing Ba or Sr cations. 
 
 From a study of the literature, one sees that the activity of the 
 ureter must be greatly influenced by chemical as well as nervous 
 influences. It seems probable, then, that a study of the influence 
 on the ureter of chemical substances which occur as normal con- 
 stituents of blood and urine compared with the effects of substances 
 appearing in these liquids when used as drugs that act on the kidney 
 (and ureter?), may give us information concerning both the function 
 of the ureter and the action of drugs. The specific influence of 
 drugs on the ureter in a normal animal cannot be precisely con- 
 trolled. However, their influences can be determined by excising 
 the organ and placing it in one of the artificial blood sera whose 
 action has been definitely ascertained. After such a determination 
 the influence of drugs under ordinary conditions can be satisfac- 
 torily recognized with due regard for other vital processes affected 
 by them. 
 
 Experiments on the excised ureter. Method. — Usually a cat or 
 small dog was chosen, which was anesthetized with ether, or bled to 
 death. The portion of the ureter to be studied was quickly isolated 
 and removed to a bath of warm physiological salt solution, where 
 
Studies of the Ureter. 269 
 
 the adjustments of such cannulas and apparatus as were to be used 
 in the particular experiment were made, one of the three following 
 methods of procedure being used : 
 
 (A) The isolated piece of ureter was ligated at both ends, one 
 end anchored at the bottom of the bath, the other to a writing lever 
 which traced on a smoked drum. 
 
 (B) The anchorage of the ureter was attained by inserting the end 
 of a curved glass cannula into the lumen of the lower end, through 
 which warm physiological salt solution was injected for the pro- 
 duction of any desired intra-ureteral pressure. The effects of the 
 contractions were not only recorded on the drum as in method A, 
 but could also be noted in the fluctuations of the fluid in the vertical 
 pressure tube. 
 
 (C) The ureter was placed horizontally in the bath, a cannula in- 
 serted in each end as in method B, and a myocardiograph attached 
 to the ureter as for recording contractions of the heart. 
 
 The effect of barium chloride on the ureter is illustrated by Ex- 
 periment 1, which was performed by technique A. 
 
 1. October 27, 1907. — Medium-sized cat, killed by decapitation. The 
 middle third of one ureter and a section of the small gut of the 
 same length as the section of ureter were excised, ligatures tied 
 to the ends of each, the sections anchored at the bottom of a beaker 
 containing Locke solution at 40 C. (through which oxygen bubbled 
 constantly), and the free end of. each attached to a spring writing- 
 lever which traced on a revolving smoked drum. 
 
 The gut began to record contractions immediately, the ureter 
 remaining perfectly motionless for forty minutes, at the end of 
 which time 1 c.c. of 5 per cent barium chloride was added to the 
 40 c.c. of Locke solution contained in the bath. The intestinal 
 contractions were immediately increased greatly. The ureter made 
 its first contraction thirty seconds after the addition, which was 
 followed by contractions occurring every twenty-five to thirty sec- 
 onds and showing for a short time a tendency to become stronger. 
 Sometimes the excursion of the recording arm was very great, the 
 succeeding pause being correspondingly lengthened. Later there 
 was a tendency for two contractions to occur in quick succession 
 or for a second to occur before the complete relaxation from the 
 first, the rate of contractions increasing, but the extent of contrac- 
 tion becoming less. As a rule, the period of resl following a double 
 contraction was greater than that following a single contraction 
 of equal extent. The contractions continued to become more fre- 
 
270 Daniel R. Lucas. 
 
 quent and less in extent until they disappeared. Subsequent addi- 
 tions of barium chloride did not cause additional contractions. 
 
 The influence o'f adrenalin on the isolated ureter as tested by the 
 same method was exhibited by a pronounced increase in tonus and 
 contractility, but often there was no stimulation of the rate of con- 
 traction ; in fact the number of contractions was often decreased, as 
 shown in Experiments 2 and 3, protocols of which are appended : 
 
 2. December 6, 1907. — An ox ureter, obtained at a slaughter-house 
 immediately after the animal had been killed by the usual method, 
 was placed in a quart jar of Ringer solution at 38 C. and carried 
 
 Figure 10. Lower tracing, time in ten seconds. Second tracing, contractions of the ureter 
 showing the effect of adrenalin chloride. 
 
 to the laboratory, where it was subjected to the treatment of 
 method B. The time that elapsed between the killing of the animal 
 and the completion of all manipulations was about forty-five 
 minutes. 
 
 During transportation of the ureter the solution in which it was 
 immersed cooled to 35 ° C. 
 
 No contraction appeared during the first ten minutes after the 
 application of method B, at the end of which time 1 c.c. of a 5 per 
 cent solution of barium chloride was added to the bath of 500 c.c. 
 of Ringer solution. Fifty seconds later the first contraction was 
 recorded. It was followed by other contractions at gradually in- 
 creasing intervals of from two seconds to two minutes. When the 
 contraction rate had become one in about two minutes, 0.2 c.c. of 
 1 : 1000 adrenalin solution were added to the bath, whereupon the 
 rate of contraction was distinctly decreased ; but the line that was 
 traced when the ureter was at rest gradually rose for fifteen 
 minutes, regardless of the contractions which had begun to show a 
 tendency to occur in groups of twos or threes (Fig. 10). 
 3. December 13, 1907. — Small dog - . Etherized. A femoral artery 
 was cannulized and the dog bled to death. The ureter was re- 
 moved and placed in 500 c.c. of Ringer solution. Method B was 
 
Studies of the Ureter. 271 
 
 applied. No intra-ureteral pressure was exerted, and only one 
 contraction took place during the first twenty minutes, which 
 seemed to be the result of irritation caused by handling the ureteral 
 cannula. The intra-ureteral pressure was then increased to 68 cm. 
 Contractions immediately appeared, and recurred fairly regularly. 
 The pressure was lowered to 50 cm., the extent of contraction be- 
 coming greater but the rate remaining about the same. The con- 
 tractions continued regularly at this rate for forty-five minutes, 
 when 0.2 c.c. of 1 : 1000 adrenalin solution was added to the bath 
 of 500 c.c. of Ringer solution. The contractions continued at the 
 previous rate for thirty-five seconds longer, then eleven contrac- 
 tions occurred in the succeeding thirty-eight seconds. After the 
 last of these, no contraction occurred for twenty-five seconds, 
 when a curve resulted which was composed of three contractions 
 and reached a height about twice that of any previously recorded. 
 This curve was followed by others of like character at the rate 
 of one per minute, but after the first three of decreasing size and 
 increasing rate, the curves showed an increasing tendency of the 
 contractions to occur in groups ( Fig. 11). 
 
 JUJUliJWil 
 
 1 
 
 ^^_^j I _j_^-il-j 1 _L->_I-U-LJ_I-J-J I .LJ U_)ULJLJUJLLJUU 
 
 Figure 11. Lowest tracing, time in ten seconds. Second tracing, ureteral contractions 
 by method B (where an intra-ureteral pressure of 68 cm. Ringer solution prevailed). 
 Third tracing, ;ntra-ureteral pressure had been reduced to 50 cm. at the mark (,) 
 02 c.c. of 1 : 1000 adrenalin solution was added to the bath of 500 c.c. of Ringer 
 solution. 
 
 In other experiments with the same technique, where the con- 
 tractions were very infrequent or entirely absent, a slightly larger 
 dose of the adrenalin than those used in the experiments described 
 in the preceding protocols caused a tonic contraction which did not 
 show any tendency to relaxation after sixteen minutes, whereupon 
 the bath was changed to plain Ringer solution. The muscle then 
 gradually relaxed, returning in five minutes to its original state. 
 
 It ^eems, from the results of the experiments with adrenalin, that 
 this substance increases both the contractility and the tone of the 
 ureter muscle. 
 
2J2 Daniel R. Lucas. 
 
 Caffein produced phenomena very similar to those caused by 
 adrenalin. Diuretin also acted in a similar way. Chloral, chloro- 
 form, ether, and magnesium sulphate were distinctly depressant, 
 showing at times a slight preliminary irritation. 
 
 In the experiments with the excised ureter by the method described 
 above, nicotin, atropin, muscarin, and physostigmin gave only nega- 
 tive results (but I feel confident that these drugs exert definite 
 influences and that they can be demonstrated graphically by im- 
 provement of the technique). 
 
 The ureteral contractions seemed to be developed less satisfac- 
 torily in oxygenated solutions than in unoxygenated ones. 
 
 The results of this study of the effects of drugs on the excised 
 ureter warrant the following conclusions : 
 
 i. Adrenalin, caffein, and diuretin increase the tone and con- 
 tractility of the ureter muscle. 
 
 2. Barium chloride increases the irritability more noticeably than 
 the substances of the first group, and does not seem to have such 
 pronounced influence on the tone, unless it is to depress it. 
 
 3. Chloral, chloroform, ether, and magnesium sulphate exert at 
 first slight irritating action, but later cause marked depression. 
 
 These observations on the excised ureter cannot be exactly ap- 
 plied to the complete ureter, however, for the middle third was 
 usually employed in rthese tests. Nerve influences would be much 
 less prominent in this portion than in other portions. 
 
 Experiments on the ureter in situ. Method. DogS were Used for 
 
 all of these experiments. Chloroform or ether was employed only 
 for the purpose of studying effects upon the ureteral peristalsis. 
 The animal was narcotized with morphine, and the ureter exposed 
 by an incision along the linea alba from symphysis pubis to ensi- 
 form cartilage. The abdominal walls were then retracted, the in- 
 testines were drawn to one side, and the viscera as well as the rest 
 of the animal were covered with warm towels and cotton. The 
 kidney was exposed by another incision along the lower border of 
 the last rib, or by a small longitudinal incision directly over the 
 kidney. The left kidney was usually selected on account of its 
 lower and more accessible position. 
 
 Graphic representations of the ureteral movements were obtained 
 as usual with a water manometer, the undulations of the column 
 of water being transmitted by means of a float and style to a re- 
 volving drum. The connections with the ureter were made by two 
 methods : 
 
Studies of the Ureter. 273 
 
 {A) By introducing into the ureter a cannula which is a modifica- 
 tion of the Ludwig-Spengler artery cannula. With this cannula a 
 much smaller incision than usual is required ; no ligation being neces- 
 sary, the propagation of the muscular wave of the ureter is only 
 slightly interfered with, the nutrient vessels of the ureter can be 
 avoided, and the nutrition of the ureter is only slightly impaired. 
 
 (B) By introducing a trocar through the kidney into the renal 
 pelvis, and retaining it in place by a purse-string suture around the 
 point of puncture of the capsule of the kidney. This also helped 
 to stop bleeding, which, however, was surprisingly slight. A small 
 quantity of warm salt solution or urine aspirated fresh from the 
 bladder was injected through the needle; thus the patency of the 
 cannula and ureter was ascertained. 
 
 In connecting the cannulas with the water manometer by means 
 of narrow glass and rubber tubing, urine was separated from the 
 water in the manometer by a column of air. Any movement of the 
 urine caused an undulation in the manometer. These undulations 
 were recorded on a drum by means of an Emerson float. 
 
 In most of the experiments of this series the ureter remained in 
 normal connection with the bladder. In some experiments, how- 
 ever, the ureter was severed near the bladder, the urine escaping 
 into the abdomen or being carried out of the body by a glass tube 
 connected with the cannula in the ureter. This cannula narrowed, 
 of course, the lumen of the ureter, and thus afforded some resist- 
 ance to the flow of urine out of the ureter. In some of the experi- 
 ments the urine was caused to drop on a pan connected with a 
 Marey tambour, by means of which the flow of urine was recorded. 
 
 The dose of morphine varied from 0.06 to 0.12 gram, depending 
 on the size of the animal. This was given subcutaneously sixty to 
 ninety minutes previous to the operation. All experiments were 
 commenced in the morning; the animals had not been fed since 
 the previous evening, but they had free access to water. 
 
 The susceptibility of the ureter, in situ, to the various substances 
 used in this study seemed to be much greater by this technique. 
 Chloroform, administered in the respired air, caused marked de- 
 e "f both the extent and frequency of the contractions of the 
 middle part of the ureter, and, if continued, completely abolished 
 them. Sometimes, when the administration was brief, the deteri- 
 orating effect did nut set in until a little while after the use of the 
 anesthetic was discontinued. Shortly after recovery from the evil 
 
274 Daniel R. Lucas. 
 
 effects of the chloroform in some of these cases, another period of 
 deterioration set in as a second after-effect. 
 
 Frequently, when ether was suddenly exhibited in the respired 
 air (inhaled per nares, not by tracheal cannula), a temporary change 
 almost instantaneously appeared in the curve representing the per- 
 istalsis of the ureter in the renal pelvis. Sometimes entire cessation 
 of the peristalsis occurred, which phenomenon could also be elicited 
 by sudden irritation of the nostrils with a probe, — an observation 
 very strongly suggestive of a reflex. 
 
 Moderate doses of caffein caused various effects in the different 
 parts of the ureter, the portion in the renal pelvis regularly con- 
 tracting in a somewhat tonic manner and causing thereby a very 
 pronounced rise in the pressure for a short time in that part. This 
 pressure appeared to be attainable through the agency of a sphincter- 
 like action of the isthmus of the ureter, which prevented the urine 
 from escaping. The pressure in the straight portion did not exhibit 
 a simultaneous change. 
 
 Adrenalin also showed a tendency to disturb the normal pressure 
 relations between the renal pelvis and the straight part of the 
 ureter. It caused a very pronounced positive pressure, very much 
 as caffein does. 
 
 Barium chloride seemed to stimulate the contractions of both the 
 upper and lower portions without the same tendency to cause in- 
 creased pressure in the renal pelvis. 
 
 When small amounts of chloral or magnesium sulphate were 
 injected into the renal pelvis, only a direct depression was shown. 
 
 These tests, while very incomplete, show distinctly that the ureter 
 is very susceptible to the action of drugs administered systemically 
 as well as directly. The experiments with chloroform suggest that 
 there may be a double action of drugs on ureteral muscular activity 
 and tone. The first influence on the peristalsis was exhibited so 
 promptly after the administration of chloroform had been begun, 
 that it could hardly have been clue to chloroform secreted into the 
 urine in amounts sufficient to affect the ureter directly, although 
 it seems possible that the circulating blood containing the drug 
 might have some such effect. When the chloroform was withdrawn, 
 at this early period, the very pronounced retardation sometimes did 
 not appear until the animal gave indications that the general sys- 
 temic action was wearing off, thus increasing the impression that 
 drugs act on the ureter not only while circulating in the blood, but 
 also when present in the urine. 
 
Studies of the Ureter. 275 
 
 From what I can find in the literature, together with impressions 
 obtained in my own studies of the ureter, it seems that drugs which 
 exert stimulating action on the ureter also appear to possess diuretic 
 power to a somewhat similar degree. I think I am correct in say- 
 ing that drugs which show a depressing action on the peristalsis 
 of the ureter also often exhibit a tendency, when administered 
 systemically, to decrease the amount of urine. These conclusions 
 suggest that stimulation or inhibition of ureteral action may be a 
 factor in the diuresis, or in the diminished flow of urine, caused by 
 drugs having the above-mentioned influences. The solution of this 
 problem presents a great many difficulties. Nevertheless it should 
 be possible to gain some information regarding it by comparing the 
 effects (on the volume of urine eliminated from each of the two 
 kidneys with both ureters intact) of drugs whose influence is emi- 
 nently diuretic and ureter-stimulating, e. g., caffein, or diuretin, 
 with the flow of urine from each kidney after the ureter of one 
 kidney has been completely eliminated. 
 
 This matter was tested in five experiments on dogs as follows: 
 
 Effects of drugs on the comparative flow of urine. — The animals 
 were narcotized with morphine and the ureters exposed only at their 
 entrance to the bladder. A small straight cannula was inserted into 
 each ureter at this location, and the urine collected in small gradu- 
 ated glass cylinders. The normal flow was noted and recorded at 
 regular intervals. 
 
 The flow from the kidneys of the same animal was found to be 
 usually quite equal. Infusion of 150 to 200 c.c. of salt solution 
 caused an average diuresis of 20 per cent from each kidney over a 
 period of thirty minutes. The actual amount of diuresis varied in 
 the different animals. Xo attempt was made to maintain uniform 
 conditions in these animals previous to the experiment. The diure- 
 sis was usually quite equal from the kidneys of the same animal. 
 
 When, however, 1 gram of diuretin, dissolved in 50 c.c. of warm 
 physiological salt solution, was infused in the femoral vein, the 
 increase in urine from each kidney was equal in the same animal, 
 but varied in different animals from between 250 to 300 per cent. 
 After these preliminary tests had been made in each animal, the 
 ureter from one of the kidneys was exposed at the renal pelvis, and 
 a large glass cannula which tlared out considerably a! its end, so 
 hold the portion of the ureter in the renal pelvis wide open, 
 was inserted and retained by means of a ligature. Such a cannula 
 
276 
 
 Daniel R. Lucas. 
 
 prevented any influence of the muscular contraction of the ureter 
 on the flow from the renal pelvis and kidney. (Great care was 
 exercised not to manipulate the kidney or interfere with the renal 
 vessels.) The urine was conducted from the cannula into the 
 graduated cylinder, care being taken to make certain that the de- 
 gree of resistance to the flow of urine from each cannula was equal. 
 This resistance varied from between 2 to 8 cm. in the different ex- 
 periments, after all manipulation was completed. The rate of flow 
 
 2 
 
 3 
 
 
 
 20 
 
 40 
 
 60 
 
 80 
 
 100 
 
 Figure 12. Upper curve gives the flow from the left kidney, lower curve that from right 
 kidney. Cannula in renal pelvis. Ureteral action was removed from the right kidney 
 at the end of 40 minutes of observation. The amount secreted was recorded at the 
 end of each 10 minutes. 0) 50 c.c. salt solution. ( 2 ) 50 c.c. salt solution. ( 3 ) 1 gm. 
 diuretin in 50 c.c. salt solution. 
 
 from each kidney was again observed, and as a rule a slight decrease 
 in flow was noted from the kidney cannulized at the renal pelvis. 
 Infusion into a femoral vein of 50 to 100 c.c of physiological salt 
 solution at this stage frequently failed to cause an increased flow 
 from the cannulized kidney, while the flow from the kidney with 
 the ureter intact showed in each experiment an increase of at least 
 200 per cent. After the flow from the kidney with its intact ureter 
 had returned to the amount eliminated previous to the infusion, 
 and the urine from each kidney was being excreted at a constant 
 
Studies of the Ureter. , 277 
 
 rate, 1 gram of diuretin was infused in 50 c.c. of physiological salt 
 solution. The average increase of the flow from the kidney with 
 intact ureter was 800 per cent for the first ten minutes, falling to 
 200 per cent in twenty minutes. From the cannulized kidney there 
 was only a 125 per cent increase in the first ten minutes with a 
 return to the normal elimination in twenty minutes (Fig. 12). 
 
 Although the damage done by the manipulation when inserting 
 the cannula into the renal pelvis cannot be overlooked as an influ- 
 ence tending to decrease the amount of urine excreted by that kid- 
 ney, the above observations suggest very strongly a ureteral influ- 
 ence in the diuresis caused by drugs which increase the muscular 
 tone and activity of the ureter. 
 
 VI. Summary of General Conclusions. 
 
 I. If continued pressure in the bladder exerts a deleterious effect 
 on the kidney, it does so by nervous influence and not by direct 
 transmission of pressure from the bladder to the kidney. 
 
 II. Even under the artificial conditions of experimental study, 
 the intra-ureteral pressure tends to remain approximately neutral 
 in the various portions of the ureter. The ureteral pressure is 
 surprisingly strong and efficient when called upon to maintain this 
 intra-ureteral condition. 
 
 The effect of the antagonism of the ureter to pressure exerted 
 in it must be carefully taken into account, especially in studies of 
 the effects of artificial pressure through the ureter on the kidney. 
 
 The vital activity of the ureter is extremely persistent. 
 
 HT. Collectively excised kidneys and ureters maintain sufficient 
 vital activity, when the kidney is perfused with warm Ringer solu- 
 tion. In permit a study of the relation of the mechanical influence 
 exerted by the meter on the circulation of the kidney. Under these 
 conditions the ureter is less susceptible to pressure influences. There- 
 fore it is not so efficienl in maintaining low-pressure conditions in the 
 renal pelvis as when in situ. 
 
 Pressure ill the renal pelvis lessens the circulation through the 
 kidiK 
 
 Sudden increase in pressure in the renal pelvis shows more pro- 
 nounced checking of the circulation than pressure of the same de- 
 vhen gradually exerted. 
 
 Retardation of renal circulation by pressure exerted in the iciial 
 
 nds to be 1 ompensated for. 
 
278 Daniel R. Lucas. 
 
 Ureteral peristalsis influences renal circulation and vice versa. 
 
 IV. Stimulation of the ureter by moderate pressure induces an 
 increased flow of urine. 
 
 Pressure exerted in the renal pelvis diminishes the flow of urine. 
 
 A pressure of 67 cm. of urine acting in the renal pelvis causes 
 distinct damage to the kidney, as shown by the presence of blood 
 in the urine, and by the macroscopical appearance of the kidney. 
 
 V. There appears to be a ureteral influence in the diuresis caused 
 by drugs which increase the muscular activity and tone of the ureter. 
 
 Professor William J. Gies made it possible for me to inaugurate 
 my work on the ureter. Since that time he has never ceased to aid, 
 encourage, and instruct me in research on this and other subjects. 
 Whatever scientific or clinical advances have or may result from 
 my efforts in research are directly dependent upon his interest and 
 assistance. 
 
BIOGRAPHICAL 
 
 Daniel Ralph Lucas resided in La Fayette, Indiana, from [88 1 
 to 1898 inclusive. He received a public school education in 
 La Fayette. In 1898 he enlisted in the 160th Regiment, Indiana 
 Volunteer Infantry, in which he served during the war with 
 Spain. He was Captain of the Hospital Corps at Purdue 
 University, 1901-1902, and Major of the 1st Batallion and Ranking 
 Cadet officer there in 1902- 1903. 
 
 At various times from 1901 to 1904 he held the position of pre- 
 scription clerk at Hogan and Johnson's, and Bartlett's pharmacies 
 in La Fayette, Indiana, and at Stork's pharmacy in Chicago, 111. 
 
 He has been assistant and subject in the Private Research 
 Laboratory of Dr. C A. Herter at various times since 1905; also 
 assistant chemist and a subject in an investigation by the U. S. 
 Dept. of Agriculture, of the effects of sodium benzoate in food on 
 human metabolism. 
 
 He was University Fellow in Biological Chemistry, Columbia 
 University, 1907- 1908, and is Fellow of the Alumni Association 
 of the College of Physicians and Surgeons, Columbia University 
 (1908- 1 909.) 
 
 He has practiced medicine in New York City since 1907. 
 
 DEGREES RECEIVED 
 
 From Purdue University — Ph. G., 1901; B.S., 1903. 
 From Columbia University — M.A., 1906; M.D., 1907. 
 
 PUBLICATIONS 
 
 Studies of the peristalsis of the ureter of the dog by the 
 graphic method. American Journal of Physiology, 1906, xvii, 
 P« 392. 
 
 Clinical aspects of recent developments in the physiology 
 and pharmacology of the ureter. New York Medical Journal ', [907 
 ( August io). 
 
 Pharmacological studies of magnesium salts. VI. (With 
 S. J. Meltzer). The Journal of Experimental Medicine \ 1907, iii, 
 p. 298. 
 
 Physiological and pharmacological studies of tin- ureter. III. 
 Journal oj Physiology, ijos.xxii, p. 245. 
 
r\ 
 
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