- Email: [email protected]
Vesicourethral Motility following Acute Spinal Cord Transection in the Cat
0022-534 7/84/1312-0370$02.00/0
Vol. 131, February Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1984 by The Williams & Wilkins Co.
VESICOURETHRAL MOTILITY FOLLOWING ACUTE SPINAL CORD TRANSECTION IN THE CAT M. HASSOUNA, C. GALEANO, M. ABDEL-RAHMAN
AND
M. ELHILALI*
From the Departments of Urology and Physiology, Centre Hospitalier Uniuersitaire, Sherbrooke, Quebec, Canada
ABSTRACT
The cause of urinary retention during the phase of spinal shock is still uncertain. In the cat with intact spinal cord, reflex voiding shows a coordination between the longitudinal and circular urethral muscles, the detrusor and the periurethral striated muscles. After transection of the spinal cord in cervical and/or thoracic segments, 26 of 28 cats failed to void. An incoordination between longitudinal, circular, detrusor and periurethral striated muscles was noticed simulating a urethro-urethral and urethrovesical dyssynergia. The 2 cats that voided 6 hours after the cord section showed a return of synergism between longitudinal, circular, detrusor and periurethral striated muscles. The conventional pharmacologic manipulation used during the early period following spinal cord transection, bethanechol chloride and phentolamine, failed to achieve proper bladder emptying because it did not correct the dyssynergic pattern. The loss of the voiding reflex immediately after spinal cord injury is frequently observed. 1· 2 Despite several studies carried out on the bladder and urethra during the spinal shock phase,3· 4 the etiology of the urinary retention is still uncertain. Some authors claim that the bladder becomes hyporeflexic or areflexic:"· 6 Others attribute the failure of voiding to an increase in the outlet resistance. 7 · 8 Lack of precision about the definition of 'spinal shock' might explain some of the discrepancies. Most of these authors measured the urethral pressure by the Brown Wickham principle 9 or by a modified Enhorning technique.10 All the animals used in their experiments were studied under anesthesia. In the present study, we attempted to clarify the mechanism involved in causing urinary retention in the cat during the early phases following spinal cord transection. MATERIALS AND METHODS
Control group (intact spinal cord). A group of 12 male cats were subjected to an intercollicular decerebration. Following craniotomy under ether anesthesia, the occipital lobes of both cerebral hemispheres were removed by suction, thus revealing the corpora quadrigemina. A deliberate transection of the brain stem was done between the superior and inferior colliculi using a blunt spatula. The ether was discontinued and the edges of the scalp incision were approximated. Decerebrate rigidity was soon shown in all cats. The level of the transection was verified on sagittal brain section fixed in formol 10 per cent and stained with Luxol fast blue. Spinal transection group. Twenty-seven male and 1 female cats weighing between 3 and 4 kg. were divided into 2 groups: 11 cats with high spinal lesion (between 5th and 6th cervical segments) and 17 cats with low spinal lesion (between 5th and 7th thoracic segments). After laminectomy at the proposed level, the spinal cord was cut under visual control and a ½ centimeter segment was removed by aspiration. In group 1 with high spinal lesion, ether anesthesia was only used during the laminectomy. By the time the cat became tetraplegic, the effect of ether disappeared and the animal was awake. In group 2 with low spinal lesion, ether was used for induction and alphaAccepted for publication August 30, 1983. Supported by a grant from the Multiple Sclerosis Society of Canada and the Medical Research Council of the University of Sherbrooke. * Requests for reprints: Dept. of Urology, Centre Hospitalier Universitaire, Sherbrooke, Que., Canada JlH 5N4. 370
chloralose, 50 to 60 mg. per kg. body weight in 0.9 per cent saline solution, was used for maintenance of the anesthesia. Experimental setup. Following the decerebration and the spinal cord section in both groups, the cat was placed on its back and a midline incision was done from the xiphisternum down to the symphysis pubis. A minimal dissection was done around the penile urethra to facilitate access to the periurethral striated muscles behind the symphysis pubis. The abdomen was opened and the rectum divided as low as possible. The intestines were packed toward the upper abdomen away from the bladder. The details of the setup were previously described.11 In brief, the simultaneous motility of the longitudinal and circular urethral smooth muscles and that of the detrusor was monitored by 3 force transducers (0.3 Grass). The vesical and urethral pressures were measured by 2 pressure transducers (Statham). The bladder and urethra were continuously perfused with 2 Harvard pumps at constant rates of 1.91 and 0.19 ml. per min. respectively. The EMG activity of the periurethral striated muscles was recorded by bipolar stainless steel wire electrodes isolated except for 2 mm. at the tip. These electrodes were inserted in the periurethral tissues at about 5 to 7 cm. from the vesicourethral junction (fig. 1). The position of the electrodes was checked by EMP response to mechanical stimulation of the tip of the penis. All tracings were simultaneously recorded on 2 Grass polygraphs (model 7D EEG and model 6ES82). The tracings were followed for periods of 1 up to 8 hours after spinal cord section. The knee jerk was tested in each animal immediately after the cord section and repeated throughout the experiment when needed. In 13 cats, we additionally recorded the intraurethral pressure about 2.5 cm. from the urethrovesical junction using a 4 F catheter with 1 side hole 4 mm. from the tip. The following components of the voiding cycle were evaluated (fig. 2): the resting intravesical pressure (A) represents the intravesical pressure (IVP) between 2 consecutive cycles, the maximum IVP being the pressure at the highest point of the detrusor cycle (B). The frequency of detrusor cycles is the number of cycles per minute. We compared these parameters in the control and the spinal section group of cats. The values reported represent the mean ± S.E. Statistical methods. Student's t test was used for comparing the significance of the results. Pharmacologic studies. The effects of the parasympathomimetic and a-adrenergic blocking agents were tested during the spinal shock phase: 1) bethanechol chloride, 0.05 µg. per kg.
371
EMG
F!G. 1. Diagram of disposition of transducers ar-ound bladder, urethra and periurethral striated muscles. CIRC and DET: force transducers recording the motility of 1v11.;1cu,,rn1a1, circular urethral smooth muscles and detrusor respectively. the direction of perfusion of the bladder. IVP: intravesical pressure recording. EMG: electromyography of periurethra! striated muscles.
/pressure
I
ca,)ac:1ty reached it appeared to be distended. The riArr,,Qfl,r muscle mowas demonstrable 30 to 45 minutes after the cord section taken to set the At a volume of 15 to 20 maximum in 11 cats varied between 15 to 28 mm. Hg with a mean of 20,l mm, Hg± 3A (S.E.); the mean IVP was 13.2 mm, Hg± 0.7 (S.K) and the mean frequency detrusor contractions was 1. 77 per min, ± 0.1 Comparing the control (intact spinal and the spinal section groups, we found no significant differences between the maximum IVP. However, the resting IVP and the frequency of detrusor contractions were significantly higher in the spinal section group (table A marked incoordination was found between detrusor, longitudinal and circular urethral muscles and sometimes the periurethral striated muscles. V esicourethral dyssynergia was particularly evident, as well as a urethra-urethral dyssynergia between the longitudinal and circular layers. This multiple dyssynergia was observed in 26 cats that did not void, In 2 cats, vesicourethral synergism returned after 6 hours and the cats voided c,µ,Jwcm.,ccv 4).
--.~=-//~~-~
L.-/-=----------/-----'-IA_'- - - - ' - B- - - ~ FAGO 2. Changes in intravesical pressure during l intravesical pressure. B, maximal intravesical pressure. pressure. D, time of detrusor wave.
TYPICAL CYClE
-----~ time A, resting differential
C!RC
weight, was used in 10 cats the i.v. route; 2) phentoiamine 1 µg. per weight i.v. was used in 6 cats. At the end of the the cord was cAµv·<>cu to the level and compl,"tE,rness of cord section. RESULTS
Control (intact cord during the constant during followed simuitaneous contraction of the the circular smooth muscle as well as a contraction of the detrusor associated with rise in the IVP. The EMG the striated muscles
in the 12 cats: the 28.6 mm, ± 3.4
TABLE
No. Cat
was 1.1 The Spinal transection reflex voiding was absent in the remaining 2, voiding occurred 6 hours later. Somatic reflexes. The EMG activity of the periurethral striated muscles was preserved in all cats after cord section. On penile stimulation, EMG response was observed as early as 15 to 20 minutes after the cord section. This response is equivalent to a persistant bulbocavernosus reflex frequently tested clinically. The knee jerk was tested within a few minutes in the cats with high cord lesion. It was present in 3, absent in 6 and equivocal in 2 cats.
l
2 3 4
5 6 7 8 9
10 11
Mean
Maximurrr intrauesical pressure decerebrated (intact spinal cord) and spinal section cats Spinai Section (Retention of Urine}*
20 20 41 20 15 12 20 21 14.4 20 18 20.1 ± 7.5 (SD) ± 2.2 (SE)
No. Cat
Intact Cord (Intact Reflex Voiding)
l
36
20
2 3 4 5 6 7 8 9
10 11 12 Mean
* Max intravesical pressure at 20 ml. ** Difference statistically nonsignificant.
**
26.l 25.5 21 20 21.7 18.4 49.1 30.3 38.2 54.5 28.66 ± 12.5 (SD) ± 3.4 (SE)
372
HASSOUNA AND ASSOCIATES TABLE 2.
(Controls) Intact Spinal Cord No.= 12 cats
Spinal Section* No.= 11 Cats
X 28.6 mm. Hg ± 3.4 (SE)
X 20.1 mm. Hg± 2.2 (SE) X 13.2 mm. Hg± 0.78 (SE) X 1.17/min. ± 0.17 (SE)
Maximal intravesical pressure Resting intravesical pressure Frequency of detrusor contraction/min.
± 0.9 (SE) 1.1/min. ± 0.1 (SE)
5 mm. Hg
p p nonsignificant p < 0.05 p < 0.001
* At bladder capacity 15-20 ml.
DYSSYNERGIA
Return of SYNERGISM
B
A
EMG ~+~tt+tt LONG~~ CIRC~
Dl:f ~ DET - ~ - - - -
I V P ~
10 sec
FIG. 4. A, dyssynergia between both smooth muscle layers of urethra and bladder with result of absence of voiding during cycles. B, return of synergism 6 hours after spinal section. Arrows mark onset of voiding in same cat.
IVP SOmmHg
IUP SOmmHg
* EMG--------~---~---~--------0
10sec Effect of
URECHOLINE
rf
EKG ll!lilll'llllllll'llll!ll!!liil I IIIJ' I llll!!!rlll!ll!ll'llill I 111111111111:11111:r11111111111::i l,lllilllllH~! I I ~ II ; ; ; , ; , , I , t t tt rrI rI; I IHlmHIHHlmm
+
LONG
FIG. 6. First 3 channels show mechanogram of longitudinal (LONG), circular (CIRC), urethral muscle and detrusor (DET). Last 3 channels show intravesical (IVP), intraurethral pressure (IUP) and electromyogram (EMG) of external sphincter. Note incoordination in motility between different urethral muscle layers (LONG and CIRC) and that of detrusor muscle (DET). Note persistantly higher intraurethral pressure (IUP) than intravesical pressure (IVP). Asterisk represents position of tip of urethral catheter (4 F) measuring urethral pressure at 1 cm. difference between each 2 marks.
DISCUSSION
CIRC
DET 10 sec
FIG. 5. Effect of bethanechol chloride, 0.04 mg./kg. body weight. Note increase in contraction in longitudinal (LONG), circular (CIRC) urethral muscles as well as detrusor (DET) augmenting dyssynergia. No voiding occurred in this cycle.
In 13 cats the intraurethral pressure was recorded, and it was found to be constantly higher than that of the bladder. The anesthesia did not seem to affect vesicourethral motility as the dyssynergic pattern was present in both high spinal unanesthetized and low spinal anesthetized groups. Pharmacologic studies. 1) Cholinergic agonists: bethanechol chloride was injected 4 to 6 hours after the spinal section. In 7 out of 10 cats, there was a marked increase in detrusor and urethral motility without voiding. In the remaining 3 cats, voiding occurred as a few drops while the intravesical pressure showed a negligible rise. The dyssynergic pattern between the urethra and bladder muscles persisted in all 10 cats injected (fig. 5). 2) a-adrenergic blocker: phentolamine mesylate was injected i.v. 4 to 6 hours after the spinal section. Voiding was not possible in 5 cats and the vesicourethral smooth muscle dyssynergia also persisted. The only cat that voided showed some relaxation in the circular muscle coat of the urethra.
We employed the experimental setup described previously for study of the voiding cycle in normal cats. In this animal model, a coordinated motility was noticed between the bladder and the 2 urethral smooth muscle layers that allowed voiding in a synergic pattern. 11 Our finding in the control group (decerebrated without anesthesia) confirmed this 'synergic pattern'. The 'spinal shock' phase is the period taken for the return of the reflex activity below the level of the cord transection. 12 In the present study, certain somatic reflexes (bulbocavernosus, knee jerk) have been found within minutes after the spinal section although the bladder was still in retention. The recuperation of somatic and vegetative reflexes does not seem to occur simultaneously, but starts quite early. The state of bladder areflexia after cord injury described by many authors was attributed to bladder overdistension, infection"i or a reflex feedback causing a spasm of the striated muscles of the pelvic floor. 14 • '" We recorded detrusor motility in less than an hour as soon as the setup was completed in cats having spinal section. During this hour, the spinal shock phase might be terminating and the bladder probably regaining some activity. The changes in the IVP were similar to those cats with intact spinal cord. Thus the bladder areflexia might not be the sole reason for the absence of reflex voiding during the spinal shock stage. The higher resting IVP in the early phase after cord section associated with an increased frequency of detrusor contractions, as compared to the control group, might suggest some incoordination of the detrusor muscle bundles and/or a dysfunction of the urethral sphincteric mechanisms. We agree with most workers that anesthetic agents have a depressing effect, though sometimes minimal on the autonomic reflexes. 2 · 3 • 6 However, on comparing group 1 and 2 of the spinal
VESICOUH.ETHRAL 1V10TILITY rt~J SPI!'¾JAL Sf-IDCK
transection experiments, the anesthesia might have a negligible depressing effect but not to the extent of contributing to the lack of reflex voiding during the early phase after spinal cord transection, as both anesthetized and nonanesthetized groups failed to void. Changes in the urethral pressure profile during spinal shock were reported as normal, 13 lowered16 or unchanged. 6 The measurements of intraurethral pressure in 11 cats having the dyssynergic pattern between the urethral smooth muscles was found to be constantly higher than that of the bladder (fig. 6). The return of the synergism in 2 cats, 6 hours after the spinal section, was associated with reflex voiding. The cholinergic agonist (bethanechol chloride) and the aadrenergic blocker (phenoxybenzamine, phentolamine) have been used alone or in combination with other agents by many authors to help bladder emptying during the spinal shock phase. Tullock and Rossier 17 showed failure of bladder emptying to be due to a rise in the proximal urethral pressure after the administration of bethanechol chloride. Others 16· 18 noticed a drop in the urethral pressure after administration of a-adrenergic blocker. We showed that these drugs were inefficient to induce voiding probably because they did not enhance the coordinating mechanism of the bladder neck opening. We suggest that inability to void and urinary retention during the 'acute' period of a spinal transection is due to the disorganization of the voiding reflexes producing inefficient bladder contraction and a double dyssynergia: vesicourethral and urethro-urethral. The conventional pharmacologic manipulation did not correct the dyssynergic pattern and failed to induce voiding.
4. 5. 6. 7.
8. 9. 10. 11.
12. 13.
14.
15. 16.
REFERENCES
17.
1. Nesbit, R. M. and Lapides, J.: Tonus of the bladder during spinal
"shock." Arch. Surg., 56: 138, 1948. 2. Holmes, G.: Observations on the paralysed bladder. Brain, 56: 383, 1933. 3. Downie, J. W. and Awad, S.: The state of urethral musculature
18.
373
during the detrusor areflexia after spinal cord transection. Invest. Urol., 17: 55, 1979. Rossier, A., Fam, B. A., Dibeneditto, M. and Sarkarati, M.: Urethrovesical function during spinal shock. Urol. Res., 8: 53, 1980. DeGroat, W. C. and Ryall, R. W.: Reflexes to several parasympathetic neurones concerned with micturition in the cat. J. PhysioL, 200: 87, 1969. Jonas, U., Jones, L. W. and Tanagho, E. A.: Recovery of bladder function after spinal cord transection. J. Urol., 113: 626, 1975. Edwardsen, P.: Nervous control of urinary bladder in cats. Acta Neurol. Scand., 43: 543, 1967. Krane, R. J. and Olsson, C. A.: Phenoxybenzamine in neurogenic bladder dysfunction. II. Clinical considerations. J. Urol., 110: 653, 1973. Brown, M. and Wickham, J. E. A.: The urethral pressure profile. Brit. J. Urol., 41: 211, 1969. Tanagho, E. A., Meyers, F. H. and Smith, D. R.: Urethral resistance: its components and implications. I. Smooth muscle component. Invest. Urol., 7: 136, 1969. Abdel-Rahman, M., Galeano, C., Lamarche, J. and Elhilali, M.: A new approach to the study of the voiding cycle in the cat. Invest. Urol., 18: 475, 1981. Kuhn, R. A.: Functional capacity of the isolated human spinal cord. Brain, 73: 1, 1950. Bradley, W. E., Chou, S. and Markman, C.: Classifying neurogenic bladder dysfunction of the urinary bladder. In: The Neurogenic Bladder. Edited by: S. Boyarsky. Baltimore, The Williams & Wilkins Co., pp. 139-146, 1971. Bors, E., Commar, A. E. and Moulton, S. H.: The role of nerve blocks in management of traumatic cord bladder: spinal anesthesia, subarachnoid alcohol injection, pudenda! nerve anesthesia and vesical neck anesthesia. J. Urol., 63: 653, 1950. Bors, E. H. and Blinn, K. A.: Spinal reflex activity from the vesical mucosa paraplegic patient. Arch. Neurol. Psycho!., 78: 339, 1957. McGuire, E. J., Wagner, F. M. and Weiss, R. M.: Treatment of dysreflexia with phenoxybenzamine. J. Urol., 115: 53, 1976. Tulloch, A. G. S. and Rossier, A. B.: The action of neuropharmacologic agents on the bladder and urethra during experimental spinal shock. Invest. Urol., 14: 312, 1977. Awad, S. A., Bryniak, S. R., Downie, J. W. and Twiddy, D. A. S.: Urethral pressure profile during the spinal shock stage in man: a preliminary report. J. Urol., 117: 91, 1977.
Vol. 131, February Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1984 by The Williams & Wilkins Co.
VESICOURETHRAL MOTILITY FOLLOWING ACUTE SPINAL CORD TRANSECTION IN THE CAT M. HASSOUNA, C. GALEANO, M. ABDEL-RAHMAN
AND
M. ELHILALI*
From the Departments of Urology and Physiology, Centre Hospitalier Uniuersitaire, Sherbrooke, Quebec, Canada
ABSTRACT
The cause of urinary retention during the phase of spinal shock is still uncertain. In the cat with intact spinal cord, reflex voiding shows a coordination between the longitudinal and circular urethral muscles, the detrusor and the periurethral striated muscles. After transection of the spinal cord in cervical and/or thoracic segments, 26 of 28 cats failed to void. An incoordination between longitudinal, circular, detrusor and periurethral striated muscles was noticed simulating a urethro-urethral and urethrovesical dyssynergia. The 2 cats that voided 6 hours after the cord section showed a return of synergism between longitudinal, circular, detrusor and periurethral striated muscles. The conventional pharmacologic manipulation used during the early period following spinal cord transection, bethanechol chloride and phentolamine, failed to achieve proper bladder emptying because it did not correct the dyssynergic pattern. The loss of the voiding reflex immediately after spinal cord injury is frequently observed. 1· 2 Despite several studies carried out on the bladder and urethra during the spinal shock phase,3· 4 the etiology of the urinary retention is still uncertain. Some authors claim that the bladder becomes hyporeflexic or areflexic:"· 6 Others attribute the failure of voiding to an increase in the outlet resistance. 7 · 8 Lack of precision about the definition of 'spinal shock' might explain some of the discrepancies. Most of these authors measured the urethral pressure by the Brown Wickham principle 9 or by a modified Enhorning technique.10 All the animals used in their experiments were studied under anesthesia. In the present study, we attempted to clarify the mechanism involved in causing urinary retention in the cat during the early phases following spinal cord transection. MATERIALS AND METHODS
Control group (intact spinal cord). A group of 12 male cats were subjected to an intercollicular decerebration. Following craniotomy under ether anesthesia, the occipital lobes of both cerebral hemispheres were removed by suction, thus revealing the corpora quadrigemina. A deliberate transection of the brain stem was done between the superior and inferior colliculi using a blunt spatula. The ether was discontinued and the edges of the scalp incision were approximated. Decerebrate rigidity was soon shown in all cats. The level of the transection was verified on sagittal brain section fixed in formol 10 per cent and stained with Luxol fast blue. Spinal transection group. Twenty-seven male and 1 female cats weighing between 3 and 4 kg. were divided into 2 groups: 11 cats with high spinal lesion (between 5th and 6th cervical segments) and 17 cats with low spinal lesion (between 5th and 7th thoracic segments). After laminectomy at the proposed level, the spinal cord was cut under visual control and a ½ centimeter segment was removed by aspiration. In group 1 with high spinal lesion, ether anesthesia was only used during the laminectomy. By the time the cat became tetraplegic, the effect of ether disappeared and the animal was awake. In group 2 with low spinal lesion, ether was used for induction and alphaAccepted for publication August 30, 1983. Supported by a grant from the Multiple Sclerosis Society of Canada and the Medical Research Council of the University of Sherbrooke. * Requests for reprints: Dept. of Urology, Centre Hospitalier Universitaire, Sherbrooke, Que., Canada JlH 5N4. 370
chloralose, 50 to 60 mg. per kg. body weight in 0.9 per cent saline solution, was used for maintenance of the anesthesia. Experimental setup. Following the decerebration and the spinal cord section in both groups, the cat was placed on its back and a midline incision was done from the xiphisternum down to the symphysis pubis. A minimal dissection was done around the penile urethra to facilitate access to the periurethral striated muscles behind the symphysis pubis. The abdomen was opened and the rectum divided as low as possible. The intestines were packed toward the upper abdomen away from the bladder. The details of the setup were previously described.11 In brief, the simultaneous motility of the longitudinal and circular urethral smooth muscles and that of the detrusor was monitored by 3 force transducers (0.3 Grass). The vesical and urethral pressures were measured by 2 pressure transducers (Statham). The bladder and urethra were continuously perfused with 2 Harvard pumps at constant rates of 1.91 and 0.19 ml. per min. respectively. The EMG activity of the periurethral striated muscles was recorded by bipolar stainless steel wire electrodes isolated except for 2 mm. at the tip. These electrodes were inserted in the periurethral tissues at about 5 to 7 cm. from the vesicourethral junction (fig. 1). The position of the electrodes was checked by EMP response to mechanical stimulation of the tip of the penis. All tracings were simultaneously recorded on 2 Grass polygraphs (model 7D EEG and model 6ES82). The tracings were followed for periods of 1 up to 8 hours after spinal cord section. The knee jerk was tested in each animal immediately after the cord section and repeated throughout the experiment when needed. In 13 cats, we additionally recorded the intraurethral pressure about 2.5 cm. from the urethrovesical junction using a 4 F catheter with 1 side hole 4 mm. from the tip. The following components of the voiding cycle were evaluated (fig. 2): the resting intravesical pressure (A) represents the intravesical pressure (IVP) between 2 consecutive cycles, the maximum IVP being the pressure at the highest point of the detrusor cycle (B). The frequency of detrusor cycles is the number of cycles per minute. We compared these parameters in the control and the spinal section group of cats. The values reported represent the mean ± S.E. Statistical methods. Student's t test was used for comparing the significance of the results. Pharmacologic studies. The effects of the parasympathomimetic and a-adrenergic blocking agents were tested during the spinal shock phase: 1) bethanechol chloride, 0.05 µg. per kg.
371
EMG
F!G. 1. Diagram of disposition of transducers ar-ound bladder, urethra and periurethral striated muscles. CIRC and DET: force transducers recording the motility of 1v11.;1cu,,rn1a1, circular urethral smooth muscles and detrusor respectively. the direction of perfusion of the bladder. IVP: intravesical pressure recording. EMG: electromyography of periurethra! striated muscles.
/pressure
I
ca,)ac:1ty reached it appeared to be distended. The riArr,,Qfl,r muscle mowas demonstrable 30 to 45 minutes after the cord section taken to set the At a volume of 15 to 20 maximum in 11 cats varied between 15 to 28 mm. Hg with a mean of 20,l mm, Hg± 3A (S.E.); the mean IVP was 13.2 mm, Hg± 0.7 (S.K) and the mean frequency detrusor contractions was 1. 77 per min, ± 0.1 Comparing the control (intact spinal and the spinal section groups, we found no significant differences between the maximum IVP. However, the resting IVP and the frequency of detrusor contractions were significantly higher in the spinal section group (table A marked incoordination was found between detrusor, longitudinal and circular urethral muscles and sometimes the periurethral striated muscles. V esicourethral dyssynergia was particularly evident, as well as a urethra-urethral dyssynergia between the longitudinal and circular layers. This multiple dyssynergia was observed in 26 cats that did not void, In 2 cats, vesicourethral synergism returned after 6 hours and the cats voided c,µ,Jwcm.,ccv 4).
--.~=-//~~-~
L.-/-=----------/-----'-IA_'- - - - ' - B- - - ~ FAGO 2. Changes in intravesical pressure during l intravesical pressure. B, maximal intravesical pressure. pressure. D, time of detrusor wave.
TYPICAL CYClE
-----~ time A, resting differential
C!RC
weight, was used in 10 cats the i.v. route; 2) phentoiamine 1 µg. per weight i.v. was used in 6 cats. At the end of the the cord was cAµv·<>cu to the level and compl,"tE,rness of cord section. RESULTS
Control (intact cord during the constant during followed simuitaneous contraction of the the circular smooth muscle as well as a contraction of the detrusor associated with rise in the IVP. The EMG the striated muscles
in the 12 cats: the 28.6 mm, ± 3.4
TABLE
No. Cat
was 1.1 The Spinal transection reflex voiding was absent in the remaining 2, voiding occurred 6 hours later. Somatic reflexes. The EMG activity of the periurethral striated muscles was preserved in all cats after cord section. On penile stimulation, EMG response was observed as early as 15 to 20 minutes after the cord section. This response is equivalent to a persistant bulbocavernosus reflex frequently tested clinically. The knee jerk was tested within a few minutes in the cats with high cord lesion. It was present in 3, absent in 6 and equivocal in 2 cats.
l
2 3 4
5 6 7 8 9
10 11
Mean
Maximurrr intrauesical pressure decerebrated (intact spinal cord) and spinal section cats Spinai Section (Retention of Urine}*
20 20 41 20 15 12 20 21 14.4 20 18 20.1 ± 7.5 (SD) ± 2.2 (SE)
No. Cat
Intact Cord (Intact Reflex Voiding)
l
36
20
2 3 4 5 6 7 8 9
10 11 12 Mean
* Max intravesical pressure at 20 ml. ** Difference statistically nonsignificant.
**
26.l 25.5 21 20 21.7 18.4 49.1 30.3 38.2 54.5 28.66 ± 12.5 (SD) ± 3.4 (SE)
372
HASSOUNA AND ASSOCIATES TABLE 2.
(Controls) Intact Spinal Cord No.= 12 cats
Spinal Section* No.= 11 Cats
X 28.6 mm. Hg ± 3.4 (SE)
X 20.1 mm. Hg± 2.2 (SE) X 13.2 mm. Hg± 0.78 (SE) X 1.17/min. ± 0.17 (SE)
Maximal intravesical pressure Resting intravesical pressure Frequency of detrusor contraction/min.
± 0.9 (SE) 1.1/min. ± 0.1 (SE)
5 mm. Hg
p p nonsignificant p < 0.05 p < 0.001
* At bladder capacity 15-20 ml.
DYSSYNERGIA
Return of SYNERGISM
B
A
EMG ~+~tt+tt LONG~~ CIRC~
Dl:f ~ DET - ~ - - - -
I V P ~
10 sec
FIG. 4. A, dyssynergia between both smooth muscle layers of urethra and bladder with result of absence of voiding during cycles. B, return of synergism 6 hours after spinal section. Arrows mark onset of voiding in same cat.
IVP SOmmHg
IUP SOmmHg
* EMG--------~---~---~--------0
10sec Effect of
URECHOLINE
rf
EKG ll!lilll'llllllll'llll!ll!!liil I IIIJ' I llll!!!rlll!ll!ll'llill I 111111111111:11111:r11111111111::i l,lllilllllH~! I I ~ II ; ; ; , ; , , I , t t tt rrI rI; I IHlmHIHHlmm
+
LONG
FIG. 6. First 3 channels show mechanogram of longitudinal (LONG), circular (CIRC), urethral muscle and detrusor (DET). Last 3 channels show intravesical (IVP), intraurethral pressure (IUP) and electromyogram (EMG) of external sphincter. Note incoordination in motility between different urethral muscle layers (LONG and CIRC) and that of detrusor muscle (DET). Note persistantly higher intraurethral pressure (IUP) than intravesical pressure (IVP). Asterisk represents position of tip of urethral catheter (4 F) measuring urethral pressure at 1 cm. difference between each 2 marks.
DISCUSSION
CIRC
DET 10 sec
FIG. 5. Effect of bethanechol chloride, 0.04 mg./kg. body weight. Note increase in contraction in longitudinal (LONG), circular (CIRC) urethral muscles as well as detrusor (DET) augmenting dyssynergia. No voiding occurred in this cycle.
In 13 cats the intraurethral pressure was recorded, and it was found to be constantly higher than that of the bladder. The anesthesia did not seem to affect vesicourethral motility as the dyssynergic pattern was present in both high spinal unanesthetized and low spinal anesthetized groups. Pharmacologic studies. 1) Cholinergic agonists: bethanechol chloride was injected 4 to 6 hours after the spinal section. In 7 out of 10 cats, there was a marked increase in detrusor and urethral motility without voiding. In the remaining 3 cats, voiding occurred as a few drops while the intravesical pressure showed a negligible rise. The dyssynergic pattern between the urethra and bladder muscles persisted in all 10 cats injected (fig. 5). 2) a-adrenergic blocker: phentolamine mesylate was injected i.v. 4 to 6 hours after the spinal section. Voiding was not possible in 5 cats and the vesicourethral smooth muscle dyssynergia also persisted. The only cat that voided showed some relaxation in the circular muscle coat of the urethra.
We employed the experimental setup described previously for study of the voiding cycle in normal cats. In this animal model, a coordinated motility was noticed between the bladder and the 2 urethral smooth muscle layers that allowed voiding in a synergic pattern. 11 Our finding in the control group (decerebrated without anesthesia) confirmed this 'synergic pattern'. The 'spinal shock' phase is the period taken for the return of the reflex activity below the level of the cord transection. 12 In the present study, certain somatic reflexes (bulbocavernosus, knee jerk) have been found within minutes after the spinal section although the bladder was still in retention. The recuperation of somatic and vegetative reflexes does not seem to occur simultaneously, but starts quite early. The state of bladder areflexia after cord injury described by many authors was attributed to bladder overdistension, infection"i or a reflex feedback causing a spasm of the striated muscles of the pelvic floor. 14 • '" We recorded detrusor motility in less than an hour as soon as the setup was completed in cats having spinal section. During this hour, the spinal shock phase might be terminating and the bladder probably regaining some activity. The changes in the IVP were similar to those cats with intact spinal cord. Thus the bladder areflexia might not be the sole reason for the absence of reflex voiding during the spinal shock stage. The higher resting IVP in the early phase after cord section associated with an increased frequency of detrusor contractions, as compared to the control group, might suggest some incoordination of the detrusor muscle bundles and/or a dysfunction of the urethral sphincteric mechanisms. We agree with most workers that anesthetic agents have a depressing effect, though sometimes minimal on the autonomic reflexes. 2 · 3 • 6 However, on comparing group 1 and 2 of the spinal
VESICOUH.ETHRAL 1V10TILITY rt~J SPI!'¾JAL Sf-IDCK
transection experiments, the anesthesia might have a negligible depressing effect but not to the extent of contributing to the lack of reflex voiding during the early phase after spinal cord transection, as both anesthetized and nonanesthetized groups failed to void. Changes in the urethral pressure profile during spinal shock were reported as normal, 13 lowered16 or unchanged. 6 The measurements of intraurethral pressure in 11 cats having the dyssynergic pattern between the urethral smooth muscles was found to be constantly higher than that of the bladder (fig. 6). The return of the synergism in 2 cats, 6 hours after the spinal section, was associated with reflex voiding. The cholinergic agonist (bethanechol chloride) and the aadrenergic blocker (phenoxybenzamine, phentolamine) have been used alone or in combination with other agents by many authors to help bladder emptying during the spinal shock phase. Tullock and Rossier 17 showed failure of bladder emptying to be due to a rise in the proximal urethral pressure after the administration of bethanechol chloride. Others 16· 18 noticed a drop in the urethral pressure after administration of a-adrenergic blocker. We showed that these drugs were inefficient to induce voiding probably because they did not enhance the coordinating mechanism of the bladder neck opening. We suggest that inability to void and urinary retention during the 'acute' period of a spinal transection is due to the disorganization of the voiding reflexes producing inefficient bladder contraction and a double dyssynergia: vesicourethral and urethro-urethral. The conventional pharmacologic manipulation did not correct the dyssynergic pattern and failed to induce voiding.
4. 5. 6. 7.
8. 9. 10. 11.
12. 13.
14.
15. 16.
REFERENCES
17.
1. Nesbit, R. M. and Lapides, J.: Tonus of the bladder during spinal
"shock." Arch. Surg., 56: 138, 1948. 2. Holmes, G.: Observations on the paralysed bladder. Brain, 56: 383, 1933. 3. Downie, J. W. and Awad, S.: The state of urethral musculature
18.
373
during the detrusor areflexia after spinal cord transection. Invest. Urol., 17: 55, 1979. Rossier, A., Fam, B. A., Dibeneditto, M. and Sarkarati, M.: Urethrovesical function during spinal shock. Urol. Res., 8: 53, 1980. DeGroat, W. C. and Ryall, R. W.: Reflexes to several parasympathetic neurones concerned with micturition in the cat. J. PhysioL, 200: 87, 1969. Jonas, U., Jones, L. W. and Tanagho, E. A.: Recovery of bladder function after spinal cord transection. J. Urol., 113: 626, 1975. Edwardsen, P.: Nervous control of urinary bladder in cats. Acta Neurol. Scand., 43: 543, 1967. Krane, R. J. and Olsson, C. A.: Phenoxybenzamine in neurogenic bladder dysfunction. II. Clinical considerations. J. Urol., 110: 653, 1973. Brown, M. and Wickham, J. E. A.: The urethral pressure profile. Brit. J. Urol., 41: 211, 1969. Tanagho, E. A., Meyers, F. H. and Smith, D. R.: Urethral resistance: its components and implications. I. Smooth muscle component. Invest. Urol., 7: 136, 1969. Abdel-Rahman, M., Galeano, C., Lamarche, J. and Elhilali, M.: A new approach to the study of the voiding cycle in the cat. Invest. Urol., 18: 475, 1981. Kuhn, R. A.: Functional capacity of the isolated human spinal cord. Brain, 73: 1, 1950. Bradley, W. E., Chou, S. and Markman, C.: Classifying neurogenic bladder dysfunction of the urinary bladder. In: The Neurogenic Bladder. Edited by: S. Boyarsky. Baltimore, The Williams & Wilkins Co., pp. 139-146, 1971. Bors, E., Commar, A. E. and Moulton, S. H.: The role of nerve blocks in management of traumatic cord bladder: spinal anesthesia, subarachnoid alcohol injection, pudenda! nerve anesthesia and vesical neck anesthesia. J. Urol., 63: 653, 1950. Bors, E. H. and Blinn, K. A.: Spinal reflex activity from the vesical mucosa paraplegic patient. Arch. Neurol. Psycho!., 78: 339, 1957. McGuire, E. J., Wagner, F. M. and Weiss, R. M.: Treatment of dysreflexia with phenoxybenzamine. J. Urol., 115: 53, 1976. Tulloch, A. G. S. and Rossier, A. B.: The action of neuropharmacologic agents on the bladder and urethra during experimental spinal shock. Invest. Urol., 14: 312, 1977. Awad, S. A., Bryniak, S. R., Downie, J. W. and Twiddy, D. A. S.: Urethral pressure profile during the spinal shock stage in man: a preliminary report. J. Urol., 117: 91, 1977.