Urinary Bladder Response to Unilateral Stimulation of Hypogastric Nerves

THE JOURNAL OF UROLOGY

Vol. 72, No. 2, August 1954 Printed in U.S.A.

URINARY BLADDER RESPONSE TO UNILATERAL STIMULATION OF HYPOGASTRIC NERVES EVERETT H. INGERSOLL, LOUISE L. JONES

AND

ERLING S. HEGRE

From the Department of Anatomy, Medical College of Virginia, Richmond, Va.

Many workers have stated that excitation of the sympathetic nerves, under certain conditions, elicited only relaxation of the bladder wall, with or without concomitant contraction of the internal sphincter (table 1). Others (Barrington, '15, '31; Courtade and Guyon, 1896; Elliott, '05, '07; Gaskell, 1886) cite experiments in which contraction of the internal sphincter was the sole response to sympathetic stimulation. Such reports have formed, no doubt, the basis for the somewhat prevalent opinion "that stimulation of the hypogastric nerves causes contraction of the internal sphincter in animals and man, accompanied by inhibition of action of the detrusor (Alpers, '50)." On the other hand, Fagge ('02) was unable to obtain any evidence of inhibitory fibers in the hypogastrics, while Langley, although he described inhibitory fibers in the bladder in 1890, came to the conclusion a few years later that stimulation of the hypogastrics caused a fall in pressure, usually, after a primary rise. Most investigators believe, as Langley did, that stimulation of the sympathetic supply produces a quick rise of bladder pressure followed, usually, by a fall of much greater extent than the original rise. Interpretations diverge at this point, however. Edmunds and Roth ('20), Langworthy, Kolb and Lewis ('40), and Scabadasch ('28), contended that the diminution in volume which resulted from stimulation of the hypogastric nerves was due solely to a contraction at the base of the bladder which was followed, usually, by relaxation of some portion of the viscus. See table 1. Some evidence has been advanced in support of this rather limited activity of the sympathetic outflow. Elliott ('07), Langworthy and Murphy ('39), and Scabadasch ('28) have stated that the motor fibers of hypogastric nerves were limited in their distribution largely to the muscle at the base of the bladder. On the other hand, Kuntz and Saccomanno ('44) found sympathetic fibers present throughout the vesical musculature in far greater numbers than would be required for the innervation of the blood vessels alone. Furthermore, the latter authors observed contraction followed by relaxation of portions of the bladder in response to stimulation of hypogastric nerves. Other workers too, have found that stimulation of the sympathetic outflow evoked contraction of the bladder wall. Some, like MacDonald and McCrea ('30), McCaughan ('37), and Stewart ('38), have reported vesical contraction as the sole response to hypogastric stimulation, while Hegre and Ingersoll ('49), Mellanby and Pratt ('39), and Wang and Harrison ('39) found, in addition, that a marked relaxation always followed the initial contraction. See table 1. A sharp distinction has been drawn by a few workers in comparing the results obtained from stimulation of intact nerves and stimulation of their peripheral Supported in part by a grant from the Veterans Administration.

178

TABLE

1. Urinary bladder response to electrical stimulation of sympathetic outflow in

cat and dog CONTRACTION

RELAXATION

I I

BY STIMULATION OF

AUTHOR 1

ANIMAL

DATE

---

Hypogastric nerves

Cat

Stewart 2

1899b

Dog

Rehfisch Zeissl

1897 1893

Cat, Dog

MacDonald & :McCrea'

1930

Dog

Zeissl

1893

Cat, Dog

McCrea & MacDonald'

1934

Nawrocki & schewsky Nussbaum

1891

Cat

Bladder

Distal cut end hypogastric nerves

Hypo gastric nerves Dog

Skabit-

1879

Wlasow

1905 I

I Bladder

II

Distal cut end hypogastric nerve Sympathetic trunk

I Dog

Mosso & Pellacani

Dog

Gianuzzi

Cat

Nawrocki & schewsky Sherrington 4

1882

I- - ~ I

1863

---

Anterior roots of lumbar spinal nerves !

i

I

I

Hypo gastric nerves

I I

I

I

Distal cut end hypogastric nerve

Skabit-

1891 1892

Dog

Gianuzzi

1863

Cat

Stewart

1899a

Cat, Dog

Dixon

1903

Cat

Stewart 4

1899a

Dog

Griffiths'

1894

Cat

Stewart'

1899a

Bladder --+ Bladder 5 Distal cut end sympathetic rami 6

---

Inferior mesenteric ganglion or plexus

Cat

Dixon Stewart'

11903 1899a

1 Preference has been given to early investigators. References to more recent literature are included in the text. 2 Stimulation when bladder was contracted. 3 During high intravesical pressure or deep anesthesia. 4 Unilateral response. 5 This relaxation followed contraction. 6 To inferior mesenteric ganglion. 7 Chiefly unilateral response.

179

180

E. H. INGERSOLL, L. L. JONES AND E. S. HEGRE

1-Continued

TABLE CONTRACTION

I

RELAXATION

I

BY STIMULATION OF

I

i

Hypogastric I nerves I

Base of Bladder

Elliott Fagge

Cat, Dog

Debaisieux

Distal cut end hypogastric nerves

Anterior roots of lumbar spinal nerves

1907 1902 1912

I

Distal cut end I Cat hypogastric nerves I Dog

Base of Bladder --; Bladder 5

I 7

I

Hypogastric nerves

I DATE ---I

Dog

I

I I I

AUTHOR1

ANIMAL

Cat

Dale Langley & Anderson 7 I

I 1906 I

1894

Hane

1898

Dale Edmunds & Roth Lewandowsky

1906 1920 1900

I Barrington I Elliott

1915 1907

Cat, Dog I Langley & Anderson

1895

Langley & Anderson

1895

Cat

Cat, Dog

cut ends. Courtade and Guyon (1896) believed that the contraction which resulted from excitation of intact hypogastric nerves was solely a reflex phenomenon. Elliott ('07), and Griffiths (1894) always sectioned the hypogastric nerves and stimulated their distal cut ends to avoid reflex changes. Stewart (1899a, 1899b) observed no difference in unilateral stimulation of an intact or sectioned nerve except that excitation of the former caused a passive bulging on the contralateral side. The majority of the workers, among them Kuntz and Saccomanno ('44), and Langley and Anderson (1894, 1895) found no essential difference in the response obtained from stimulation of intact nerves or of their peripheral cut ends. See table 1. Most workers believe that a hypogastric nerve supplies only the corresponding side of the bladder. A strictly unilateral response was observed by Griffiths (1894), and Stewart (1899a), upon excitation of the distal cut end of a hypogastric nerve. See table 1. Sherrington (1892) obtained a similar result following stimulation of anterior lumbar roots of spinal nerves. Debaisieux ('12), MacDonald and McCrea ('30), and Langley and Anderson (1894) reported a slight contraction on the contralateral side in addition to the usual homolateral response. After an extensive review of the literature Gruber ('33) came to the conclusion that the bladder response evoked on excitation of the distal cut end of a hypogastric nerve was limited in its effect to the corresponding half of the viscus and affected equally all portions of the detrusor muscle. It is apparent that there is need for more precisely determined information on the pattern of response evoked by activity of the sympathetic outflow.

HYPOGASTRIC NERVE STIMULATION

181

Previously, using the method devised for measuring the regional activity of the bladder (Hegre and Ingersoll, '49), it was found that all regions of the bladder participate in the diphasic response following bilateral stimulation of the sympathetic outflow and, in addition, that all portions of the viscus exhibit spontaneous activity (Ingersoll and Hegre, '51). The present study was undertaken to ascertain the behavior of the detrusor muscle in response to unilateral stimulation of hypogastric nerves. METHODS

Adult cats, anesthetized with 20 mg. Dial (Ciba) and 50 mg. chloralosane (per kg., i. p.), were used. Following a midventral abdominal incision to expose the hypogastric and pelvic nerves the bladder was rotated so that the posterior surface was uppermost. On this surface ,vere placed small squares of white adhesive paper each bearing a small black spot in its center. The paper squares were arranged so as to divide this surface into quadrants and segments (fig. 1). By means of a Cine-kodak Special 16 mm. camera, mounted above the bladder, photographs were taken at 1 sec. intervals during the course of each observation. Subsequently, by projecting the film onto suitable paper, measurements were made and the results plotted of the activity taking place per unit length of muscle in each segment during each sec. of observation. In addition, a kymograph record was kept of the total bladder response under conditions of constant pressure (Hegre and Ingersoll, '49). A square wave stimulator (Grass) was used in all experiments with the instrument set to discharge at a frequency of 20-30 per sec., a 2 msec. delay and at a duration rate of 5 msec.

C

Fm. 1. Schematic drawing of exposed surface of bladder showing location of quadrants and segments.

182

E. H. INGERSOLL, L. L. JONES AND E. S. HEGRE

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Fm. 2. Bladder responses in cat 2, exp. 11. Unilateral stimulation of a hypogastric nerve with all nerves to the bladder intact. Intravesical pressure held constant at 14 cm. water. Figures 2-7 are graphic records of muscle activity taking place in each bladder segment in response to unilateral stimulation of hypogastric nerves. Each circle represents activity taking place during each second of observation. Onset of stimulation coincides with first circle of each curve while cessation of stimulation is indicated by an upward pointing arrow (except in fig. 7, upper curves, where period of stimulation was 59 sec.). A downward pointing arrow indicates side of bladder stimulated. A cross-bar through a nerve indicates section of that nerve. Insert: kymograph record of each observation, together with the time of stimulation. Abbreviations: H, hypogastric nerve; P, pelvic nerve; Al, A2, Bl, etc., bladder segments. RESULTS

1. Effect of iinilateral stimillation of hypogastric nerves with all nerves to the bladder intact. Unilateral stimulation resulted in a prompt diphasic response of the detrusor muscle on the corresponding side (figs. 2, 3, 4). The period of initial contraction lasted from 8 to 15 sec. and was followed immediately by relaxation in the same regions. On the contralateral side several types of responses occurred. The one most frequently observed was similar to that recorded on the stimulated side. In some instances the initial contraction was very brief and was followed by a prolonged relaxation (fig. 3, Dl, upper curve; fig. 4, Bl, upper curve). Another type of response had a latent period of 1 to 3 sec. before the onset of contraction (fig. 3,

183

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Fm. 3. Bladder responses in cat 9. Unilateral stimulation of hypogastric nerves with all nerves to the bladder intact. Upper curves, closed circles (exp. 1), right hypogastric nerve stimulated; lower curves, open circles (exp. 2), left hypogastric nerve stimulated. Intravesical pressure held constant at 16 cm. water.

Al, lower curve; fig. 4, Cl, upper curve and B2, lower curve). In some regions the detrusor muscle relaxed during this period of initial delay (fig. 2, Dl; fig. 4, 02, upper curve). In the remainder of the responses relaxation of the detrusor was pronounced and occurred without the usual initial contraction (fig. 3, Cl, Dl, lower curve; fig. 4, Bl, Cl, 02, Dl, lower curve). The amount of initial contraction per unit length of muscle, following unilateral stimulation of intact nerves, showed considerable variation. In one experiment (fig. 8, 02 No. 11) the average amount of contraction in the homolateral and contralateral halves of the viscus was about equal, while in the other studies in this series (fig. 8) marked differences were evident. In two observations from cat 9 stimulation of the right hypogastric nerve (09 No. 1) elicited a greater response than when the left nerve was excited (09 No. 2). Similar studies in cat 4 (04 No. 2, 04 No. 4) also evoked contrasting reactions. Relaxation without previous contraction was a notable feature on the contralateral side in two of these bladder studies (09 No. 2; 04 No. 4).

184

E. H. INGERSOLL, L. L. JONES AND E. S. HEGRE

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Frn. 4. Bladder responses in cat 4. Unilateral stimulation of hypogastric nerves with all nerves to the bladder intact. In upper curves, closed circles (exp. 2) left hypogastric nerve stimulated; in lower curves, open circles (exp. 4) right hypogastric nerve stimulated. Intravesical pressure held constant at 27 cm. water.

2. Effect of unilateral stimulation of intact hypogastric nerves after section of the pelvic nerves. Unilateral stimulation of an intact hypogastric nerve following section of the pelvic nerves gave a prompt and unusually vigorous response in all regions of the corresponding half of the viscus (fig. 5). On the opposite side similar responses were noted in segments Al, Dl, B2, while in the other areas contraction occurred after a short latent period. The amount of contraction per unit length of muscle was considerably greater on the stimulated side than on the opposite side (fig. 9, C9 No. 11). 3. Effect of unilateral stimulation of the distal cut end of a hypogastric nerve with the opposite hypogastric nerve intact and with the pelvic nerves sectioned. The response on the stimulated side (fig. 6) was a prompt contraction followed by relaxation. On the opposite side all portions of the detrusor muscle exhibited an initial contraction which was followed by relaxation in the same regions but most of the responses were weak or were delayed 1 to 3 sec. The average amount of contraction per unit length of muscle was much greater on the stimulated side than on the opposite side (fig. 9, C9 No. 13).

185

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4. Ejfect of unilateral stimulation of the distal cut end of a hypogastric nerve with the opposite hypogastric nerve and the pelvic nerves sectioned. The two studies (fig. 7) are from the same cat and differ from each other only in the side stimulated (right nerve, C9 No. 19; left nerve, C9 No. 16). In both observations contraction occurred in all homolateral and in many contralateral segments. This response was often delayed or was preceded by an initial relaxation on the contralateral side. The amount of contraction per unit length of muscle following stimulation of the distal cut end of the left hypogastric nerve (fig. 9, C9 No. 16) was about the same on both sides of the bladder. Stimulation of the distal cut end of the right hypogastric nerve (fig. 9, C9 No. 19), however, evoked a much greater contraction on the stimulated side than on the opposite side and, in addition, the overall contraction was more vigorous when compared to stimulation of the left nerve. DISCUSSION

Data have been presented showing that unilateral stimulation of hypogastric nerves elicited responses, not only on the corresponding side, but on the opposite

186

E. H. INGERSOLL, L. L. JONES AND E. S. HEGRE

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side of the bladder as well. On the stimulated side there always was a reasonably prompt contraction of the detrusor muscle which was followed usually by relaxation in the same regions. No particular area on the stimulated side could be said to be more active than any other region. On the contralateral side of the viscus unilateral stimulation evoked more than one type of response. Slightly over half were similar to those observed on the stimulated side. In some regions, especially near the fundus, the contractions were of extremely short duration and were usually followed by prolonged relaxation. Another type of response recorded from the contralateral side had a latent period of from 1 to 4 sec. before the onset of contraction. As a rule, the contraction when it appeared was vigorous and was followed by the customary relaxation. Sectioning of the nerves and stimulation of their distal cut ends had a tendency to delay the onset of contraction. In a few regions the initial contraction was preceded by a very brief relaxation. In other areas this relaxation persisted throughout the period of stimulation. The amount of contraction per unit length of muscle varied within wide limits in the same and different bladder studies. In one series of observations from the

187

HYPOGASTRIC NERVE STIMULATION

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same cat (C9) stimulation of the right hypogastric nerves regularly elicited a greater contraction, in both halves of the viscus, than stimulation of the hypogastric nerves on the left side. This held true following excitation of intact nerves or of their peripheral cut ends. In two studies from another cat (C4) similar results were recorded. In all of the studies, irrespective of the side stimulated, the average amount of contraction on the homolateral side always exceeded, though sometimes only slightly, the average amount of contraction obtained from the contralateral side. The least responsive areas in any single observation were always on the contralateral side, generally along the lateral margin and adjacent to, or within, the fundic portion of the viscus. One factor which was thought by many workers to influence the amount of contraction and subsequent relaxation was the intravesical pressure at the onset of stimulation. McCrea and MacDonald ('34) regularly elicited inhibition of vesical activity upon stimulation of the hypogastrics at a good level of pressure. They, as well as Mellanby and Pratt ('39), found that when the intravesical pressure was low, bladder contractions were obtained. According to the latter investigators, if the pressure was then raised and the same stimulus applied, the

188

E. H. INGERSOLL, L. L. JONES AND E. S. HEGRE

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SEQUENCE OF

SEGMENTS· CONTRALATERAL SIDE: Al,Bl,Cl,Dl,B2,C2

SEQUENCE OF

SEGMENTS- HOMOLATERAL SIDE" 83,C3,A2,B4,C4,D2

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40

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HYPOGASTRIC NERVE STIMULATION

189

initial contraction obtained was small and the subsequent relaxation large. In our experiments the amount of pressure within the bladder seemed to have little effect upon the amount of contraction and subsequent relaxation but we did obtain marked differences in the amount of contraction by stimulating different sides of the same bladder. In a previous report (Hegre and Ingersoll, '49) evidence was advanced to show that the prestimulatory volume was of greater significance than the intravesical pressure in determining the amount of contraction and resulting relaxation. The responses which have been obtained from unilateral stimulation of intact nerves and of their distal cut ends indicate a much more extensive bilateral inervation of the detrusor muscle than has been suggested heretofore. It is reasonable to assume from these data that all regions of the viscus are supplied by each hypogastric nerve. However, the richness of the supply is variable, not only to the contralateral side, but to the same side as well. SUMMARY

Unilateral stimulation of hypogastric nerves always elicited on the corresponding side a prompt contraction of all portions of the detrusor muscle which was followed immediately by relaxation in the same regions. On the opposite side slightly over one-half of the responses, following unilateral stimulation of hypogastric nerves, were similar to those observed on the stimulated side. Another group of responses had a latent period of from 1 to 4 sec. before the onset of contraction. Sectioning of the nerves and excitation of their distal cut ends had a tendency to lengthen the latent period. In the remainder of the responses elicited from the contralateral side the initial reaction was one of relaxation. In some regions this was followed by contraction and subsequent relaxation; in others, relaxation was the only response. The amount of contraction per unit length of muscle in response to unilateral stimulation varied within wide limits in the same and different bladders. Sectioning of the nerves or altering the intravesical pressure did not materially affect the result. The average amount of contraction on the homolateral side always exceeded that obtained from the opposite side. The least responsive areas in any single observation were on the contralateral side, generally along the lateral margin and adjacent to or, within, the fundic portion of the bladder. These studies indicate a much more extensive bilateral innervation of the detrusor muscle by hypogastric nerves than has been previously suggested. All areas of the bladder wall were found to be supplied by each hypogastric nerve but the richness of this innervation was quite variable, especially on the contralateral side, near the lateral margin of the viscus. REFERENCES ALPERS, B. J.: Clinical Neurology. Philadelphia: F. A. Davis Co., 1950, 2nd ed. BARRINGTON, F. J. F.: Quart. J. Exper. Physiol., 8: 33, 1915. BARRINGTON, F. J. F.: Proc. Royal Soc. Med., 25: 557, 1931. CouRTADE, D. AND GUYON, J. F.: Arch. de Physiol. norm. et path., 8: 622, 1896. DALE, H. H.: J. Physiol., 34: 163, 1906. DEBArsrnux, G.: Nevraxe, 13: 119, 1912. DrxoN, W. E.: J. Physiol., 30: 97, 1903. EDMUNDS, C. W. AND ROTH, G. B.: J. Pharm. and Exper. Therap., 15: 189, 1920. ELLIOTT, T. R.: J. Physiol., 32: 401, 1905.

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E. H. INGERSOLL, L. L. JONES AND E. S. HEGRE

ELLIOTT, T. R.: J. Physiol., 35: 367, 1907. FAGGE, C. H.: J. Physiol., 28: 304, 1902. GASKELL, W. H.: J. Physiol., 7: 1, 1886. GIANuzzI, J.: J. de la Physiol., 6: 22, 1863. GRIFFITHS, J.: J. Anat. and Physiol., 29: 61, 1894. GRUBER, C. M.: Physiol. Rev., 13: 497, 1933. HANc, A.: Archiv f. d. ges. Physiol., 73: 453, 1898. HEGRE, E. S. AND INGERSOLL, E. H.: J. Urol., 61: 1037, 1949. INGERSOLL, E. H. AND HEGRE, E. S.: J. Urol., 66: 758, 1951. KUNTZ, A. AND SAccoMANNO, G.: J. Urol., 51: 535, 1944. LANGLEY, J. N.: J. Physiol., 12: 23, 1890. LANGLEY, J. N.: J. Physiol., 27: 237, 1901. LANGLEY, J. N. AND ANDERSON, H.K.: J. Physiol., 16: 410, 1894. LANGLEY, J. N. AND ANDERSON, H.K.: J. Physiol., 19: 71, 1895. LANGWORTHY, 0. R., KoLB, L. C. AND LEWIS, L. G.: Physiology of Micturition. Baltimore: Williams and Wilkins, 1940. LANGWORTHY, 0. R. AND MURPHY, E. L.: J. Comp. Neur., 71: 487, 1939. LEWANDOWSKY, M.: Centralbl. f. Physiol., 14: 433, 1900. MACDONALD, A. D. AND McCREA, E. D.: Quart. J. Exper. Physiol., 20: 379, 1930. McCAUGHAN, J.M.: J. Missouri State Med .. Assoc., 34: 379, 1937. McCREA, E. D. AND MAcDoNALD, A. D.: Brit. J. Urol., 6: 119, 1934. MELLANBY, J. AND PRATT, C. L. G.: Proc. Royal Soc. Lond., 127: 307, 1939. Mosso, A. AND PELLACANI, P.: Arch. ital. de Biol., 1: 291, 1882. NAWROCKI, F. AND SKABITSCHEWSKY, B.: Arch. f. d. ges. Physiol., 48: 335, 1891. NussBAUM, H.: Arbeiten du Lab. du med. Faculitat i.n Warschau, 5: 120, 1879. REHFISCH, E.: Arch. f. path. Anat. u. Physiol., 150: Ill, 1897. ScABADASCH, A.: Ztschr. f. Anat. u. Entwg., 86: 730, 1928. SHERRINGTON, C. S.: J. Physiol., 13: 621, 1892. STEWART, C. C.: Am. J. Physiol., 2: 182, 1899a. STEWART, C. C.: Am. J. Physiol., 3: 1, 1899b. STEWART, J.C.: Quart. J. Exper. Physiol., 27: 193, 1938. WANG, S. AND HARRISON, F.: Am. J. Physiol., 125: 301, 1939. WLAsow, N. S.: Centralbl. f. Physiol., 18: 776, 1905. ZEISSL, M.: Arch. f. d. ges. Physiol., 53: 560, 1893.