INNERVATION OF THE STRIATED MUSCLE OF THE MEMBRANOUS URETHRA OF THE MALE DOG

Purpose

To identify the functional innervation of the striated muscle layer of the post-prostatic urethra of male dogs.

Materials and Methods

Detailed anatomic dissection of the pelvic and pudendal nerves was carried out. The pressure and contractile responses to stimulation of these nerves were recorded in vivo and in vitro.

Results

Small branches of the pelvic nerve entered the membranous urethra but passed through the striated muscle to the inner smooth muscle layer. Stimulation of the nerve with 1 msec pulses at 10 Hz produced a slow contraction of the urethra which was unaffected by d-tubocurarine. Pudendal nerve branches entered the striated layer from the caudal end. Stimulation produced a rapid, visible contraction that was abolished by d-tubocurarine. Field stimulation of isolated strips of striated muscle resulted only in rapid, d-tubocurarine sensitive contractions.

Conclusions

The striated muscle of the membranous urethra is innervated exclusively by the pudendal nerve.     

Anatomic and functional studies of the male and female urethral sphincter

A total of 28 human specimens (14 male, 14 female) was used to perform macro- and microscopic studies on the morphologic basis of the urethral continence mechanism. Furthermore, functional studies were performed in six sheep, with the aim of looking at the pudendal and autonomic innervation of the urethra and the rhabdosphincter, as well as the changes of autonomic innervation after selective denervation. Transurethral ultrasound was performed in 34 continent patients, in order to visualize the contractions of the rhabdosphincter. The membranous urethra is innervated by branches of the autonomic pelvic plexus. The rhabdosphincter is an omega-shaped loop of striated muscle fibers that is innervated by the pudendal nerves. These results are supported by the results of animal experiments that show that the autonomic nerves predominantly innervate and regulate the upper part of the urethra, whereas stimulation of the pudendal nerves leads to a contraction of the lower part of the sheep urethra. In electron-microscopy, marked degeneration of the smooth muscle cells could be seen in the sheep with bilateral denervation.     

Spinal cord lesions at different levels affect either the adrenergic or vasoactive intestinal polypeptide-immunoreactive nerves in the human urethra

The urethras from 1 patient with cervical (C1-2) and 2 patients with thoracic (T10) spinal cord lesions were studied histochemically and immunohistochemically for adrenergic and vasoactive intestinal polypeptide-immunoreactive nerves. Dense vasoactive intestinal polypeptide-immunoreactive but not adrenergic nerves were found in the urethral smooth muscle, around the blood vessels and at the base of the mucosa in the patients with thoracic lesions. In contrast, adrenergic but not vasoactive intestinal polypeptide-immunoreactive nerves were found associated with the smooth muscle of the urethra and around the blood vessels in the patient with a cervical lesion. In patients with cervical or thoracic lesions neither adrenergic nor vasoactive intestinal polypeptide-immunoreactive nerves were found around striated muscle fibers of the intrinsic external urethral sphincter. The results are discussed in relation to the possible function of these nerves in the urethra of patients with autonomic dysreflexia and detrusor-sphincter dyssynergia.     

Urethral function after cystectomy: a canine in vivo experiment

Summary To study the function of the pelvic floor and the isolated urethra after removal of the bladder, 5 male and 5 female mongrel dogs were used in an acute in vivo experiment. Urethral pressure changes secondary to unilateral stimulation of the pelvic and pudendal nerves were recorded. After baseline data of the intact system were documented, the following procedures were carried out: separation of the urethra from the bladder neck (prostate), nerve-sparing cystectomy (cystoprostatectomy), and cold-knife incision through the entire length of the proximal urethra. Pressure recordings were repeated after each step of surgery. Pudendal nerve stimulation resulted in rapid and large pressure rises in the distal urethra (reaction typical of striated muscle). This response remained unchanged after all three surgical steps. Pelvic nerve stimulation provoked pressure rises within the urethra of a pattern typical of smooth muscle. The findings persisted after separation of the urethra from the bladder neck (prostate) and after cystectomy, but were not observed after urethrotomy. Contractions secondary to pudendal nerve stimulation were inhibited by curare, which did not affect the reaction to pelvic nerve stimulation. Our experiments demonstrate that in the dog the continuity of bladder and urethra is not required for the function of urethral closure mechanisms. The contractile potency of the urethral smooth muscles remains intact after nerve-sparing cystectomy. We believe that problems with the baseline continence of surrogate bladders should mainly be ascribed to a lack of surgical caution in preserving the autonomic nerves of cystectomy. A poor response to stress conditions cannot be explained by damage to the neural pathway of the striated sphincter, as the pudendal nerve is not at risk during nerve-sparing cystectomy. In our opinion mechanical malfunction of the striated muscle components secondary to scarring at the site of the anastomosis is the main reason for stress incontinence after orthotopic bladder replacement.     

Intramural ganglia in the human urethra

The urethras from five patients with a thoracic or cervical spinal cord lesion and one patient with carcinoma of the bladder were studied immunohistochemically for neuropeptide Y and vasoactive intestinal polypeptide. Autonomic ganglia, containing two to 21 nerve cell bodies, were found in the smooth and striated muscle regions of the intrinsic external urethral sphincter; they were present rarely in the distal urethra and were absent from the prostatic urethra. Neuropeptide Y immunoreactivity was observed in some of the nerve cell bodies (diameter 25 to 50 microns). Vasoactive intestinal polypeptide immunoreactivity was observed in small cells (diameter 15 to 25 microns.) in the urethral smooth muscle and in the walls of blood vessels that resembled small intensely fluorescent cells but may be nerve cell bodies. Both neuropeptide Y- and vasoactive intestinal polypeptide-immunoreactive nerve fibres were found in the smooth muscle and around blood vessels in the urethra of all patients. Both types of peptide-containing nerves were found associated with striated muscle of the intrinsic external urethral sphincter in patients with spinal cord injury, but only vasoactive intestinal polypeptide-immunoreactive nerves were found in the patient with carcinoma of the bladder in this region. The functions of the autonomic ganglia and vasoactive intestinal polypeptide- and neuropeptide Y-immunoreactive nerves in the human urethra remain to be elucidated.     

Perineal nerve and transcutaneous spinal stimulation: new methods for investigation of the urethral striated sphincter musculature

The distal motor latencies in the perineal and pudendal nerves were measured in 20 normal subjects using digitally directed pudendal nerve stimulation. The mean pudendal and perineal nerve latencies were 1.9 ms +/- 0.2 (SD) and 2.4 ms +/- 0.2 (SD) respectively. In a further eight normal subjects transcutaneous spinal stimulation was used to record the motor latency from L1 and L4 stimulation sites to the urethral striated sphincter musculature. The mean spinal nerve terminal latencies from L1 and L4 were 4.9 ms +/- 0.3 (SD) and 4.1 ms +/- 0.2 (SD) respectively. These techniques can be applied to the investigation of the nerve supply to the urethral striated musculature in stress urinary incontinence and other disorders affecting the innervation of the anterior pelvic floor musculature.     

Role of striated and smooth muscle components in the urethral pressure profile in traumatic neurogenic bladders: a neuropharmacological and urodynamic study. Preliminary report

Urodynamic investigations with urethral pressure profile, and vesical, intrarectal and anal pressure recordings were performed in 37 patients with spinal cord lesions. The recordings were done before and after phentolamine injections and/or pudendal nerve blocks to evaluate the respective contribution of sympathetic and somatic innervation to the maximum urethral closure pressure in the mid and distal portions of the membranous urethra. A pressure gradient was demonstrated in the membranous urethra with higher values in the distal than in the mid portion. These results emphasize that the interrupted withdrawal technique is superior to the continuous technique in patients with upper motor neuron bladders. Mid urethral striated and smooth muscle components were shown to represent approximately 60 and 30 per cent of the maximum urethral closure pressure, respectively. In the distal urethra striated and smooth components are more abundant than in the mid portion and contribute in equal proportion to the maximum urethral closure pressure. No substantial role was found for the vascular bed in the maximum urethral closure pressure. The greatest pressure decrease in the mid and distal urethra of patients with lower motor neuron bladders was believed to be an effect of denervation supersensitivity. The results of pudendal blocks showed sphincter dyssynergia to be mediated through pudendal nerves via spinal reflex arcs. Phentolamine effects on bladder activity suggest that blockade of alpha-adrenergic receptors inhibits primarily the transmission in vesical and/or pelvic parasympathetic ganglia and acts secondarily through direct depression of the vesical smooth muscle. Our neuropharmacological results raise strong doubts as to the existence of a sympathetic innervation of the striated urethral muscle in humans.     

Continence and some properties of the urethral striated muscle of male greyhounds

OBJECTIVE: To determine the properties of the striated muscle of the greyhound (dog) urethra and to consider its role in maintaining continence. Materials and methods The thickness of the muscle layers and the muscle types were determined by examining sections stained with haematoxylin and eosin or Masson's trichrome. These factors were correlated with the mechanical and electrical responses of muscle strips to nerve stimulation, and compared with muscle from other breeds of dog and other parts of the animal. RESULTS: The striated muscle formed approximately 70% of the membranous urethra and was predominantly (68%) type IIa muscle (i.e. fast but fatigue-resistant). The mean resting membrane potential was -74 mV; nerve stimulation produced an action potential with a mean amplitude of 97 mV and contraction lasting about 200 ms. All responses were abolished by D-tubocurarine. The contractions were well maintained with continuous or intermittent stimulation. The properties were intermediate between those of the anconeus (slow) and the extensor carpi radialis (fast) muscles. CONCLUSIONS: The distribution, fibre type and contractile characteristics would enable the striated urethral muscle to maintain tension for continence at rest and provide additional continence during sprints.     

Evidence for the existence of a urethro-urethral excitatory reflex in urethane anesthetized rats: involvement of peripheral ganglionic structures.

In urethane-anesthetized rats urethral distension with saline at the level of the external urethral sphincter elicited a series of slow phasic contractions with an amplitude between two and 18 mm. Hg. Contractions having an amplitude lower than four mm Hg were unaffected by i.v. or topical hexamethonium (HEX) or by topical tetrodotoxin (TTX). HEX or TTX transiently abolished or reduced the distension-evoked contractions having an amplitude between four and 18 mm. Hg. Administration of d-tubocurarine (d-Tc), atropine, bilateral section of pudendal nerves, spinalization (T12-S1) or bilateral removal of the major pelvic ganglia did not modify the distension-induced rhythmic urethral activity. In rats desensitized to capsaicin (four days before), both amplitude and frequency of urethral contractions did not differ from control value. In rats pretreated with atropine, administration of HEX still inhibited the distension-induced urethral contractions. Intravenous dimethylphenylpiperazinium (DMPP) triggered a rapid phasic contraction with an amplitude ranging between 15 and 25 mm. Hg. This effect was inhibited by previous administration of HEX. In accordance with histochemical studies showing spherical ganglionic cell bodies between the outermost striated muscle layer and the smooth muscular coat, present data indicate that distension of the external urethral sphincter reflexly activates urethral contractions, possibly through a local mechanism.     

Contractile properties of the proximal urethra and bladder in female pig: morphology and function

AIMS: To compare the contractile properties of proximal urethral and bladder muscle of the female pig. MATERIALS AND METHODS: In two proximal segments (I and II) of the urethra, small muscle bundles were excised to measure the force-length (maximum force) and the force-velocity (unloaded shortening velocity) relation using the stop-test. The rate of force development was calculated using phase plots. Contractile properties of urethral and bladder segments were statistically compared using the Mann-Whitney U-test. Immunohistochemical staining of whole circumference urethral cross sections was used to identify the location of smooth and striated muscle fibres. RESULTS: On isometric force development, the urethral muscle bundles revealed a fast ( approximately 0.5 sec) and a slow ( approximately 2.1 sec) time constant, whereas in bladder only a slow ( approximately 2.3 sec) component was measured. On average, isometric force was highest in bladder. The length range over which force was produced was smallest in urethral segment II, followed by urethral segment I and finally bladder. The unloaded shortening velocity was 0.15, 0.25 and 0.35 1/sec, respectively. Histological preparations showed that smooth as well as striated muscle was present in proximal urethra. In urethral muscle bundles, spontaneous contractions were measured with a frequency of 0.4 Hz. CONCLUSIONS: Differences in contractility found between urethra and bladder may be ascribed to the presence of striated muscle in the proximal urethra. The regulation of tone and spontaneous contractions may be part of the continence mechanism in the female pig urinary tract.     

Adrenergic innervation of the striated muscle of the intrinsic external urethral sphincter from patients with lower motor spinal cord lesion

The adrenergic innervation of smooth and striated muscle components of the intrinsic external urethral sphincter from patients with suprasacral lesions and detrusor-sphincter dyssynergia has been described previously, when no adrenergic nerves were found associated with striated muscle fibers. In our study the intrinsic external urethral sphincter from patients with lower motor neuron lesions and detrusor areflexia was studied histochemically using the glyoxylic acid method to visualize catecholamines. Varicose adrenergic nerves were demonstrated in the smooth muscle. Adrenergic nerve fibers also were found along the edge of individual striated muscle fibers as well as around striated muscle bundles. Blood vessels in both regions of the urethral sphincter were innervated by adrenergic nerves. We conclude that in patients with lower motor neuron lesions and detrusor areflexia there is a substantial invasion by adrenergic nerve fibers in relation to smooth and striated muscle in the urethra, although the function of the nerve fibers is not known.     

The motor nerve supply of the external urethral sphincter muscles: An electrophysiologic study

The term “intrinsic external urethral sphincter” has recently been applied to the striated muscle immediately surrounding the membranous urethra, thus distinguishing and separating it from the periurethral striated muscle which is a component of the pelvic floor. The innervation of the intrinsic external urethral sphincter is still controversial. Six male patients with a sustained spinal cord lesion above D-4 underwent electrophysiological evaluation of the reflex and direct evoked responses to stimulation of the pudendal nerve branches in the perineal region. Recording of the motor unit potentials was performed using a catheter-mounted concentric needle introduced into the intrinsic external urethral sphincter transurethrally. The results of this study indicate that the pudendal nerve, i.e., somatic, plays an important role in the innervation of the intrinsic external urethral muscle. It does not, however, exclude the possibility that the autonomic nervous system also innervates this muscle.     

Ipsilaterality of motor innervation of canine urethral sphincter

The functional activity of the sphincter muscle of the urethra is known to be controlled largely by the hypogastric and pudendal nerves. It remains unknown, however, whether innervation of the muscle by these peripheral nerves is ipsi- or bilateral. In an attempt to answer this question urethral closure pressure was determined simultaneously in the anterior, posterior, right and left portions of urethral wall in dogs. The pressure measurements were stereographed with the aid of a computer (stereo-UPP) and by this means the effect of unilateral section or electrical stimulation of hypogastric and pudendal nerves on the intraurethral pressure profile was analyzed. Unilateral section or electrical stimulation of the hypogastric nerve, distal to its division, produced a fall and a rise primarily in proximal intraurethral pressure, respectively, in all four directions. There was no significant difference in this response between the involved and uninvolved sides. Unilateral section of the pudendal nerve resulted in a fall primarily in distal intraurethral pressure in all four directions. No significant difference was present between the injured and noninjured sides. In contrast, electrical stimulation of the pudendal nerve distal to the point of its division caused a rise in intraurethral pressure in all four directions, with a significantly greater pressor response on the stimulated than on the nonstimulated side. These observations suggest decussating motor innervation of the urethra by the hypogastric nerves and also the possibility of the distal urethra being ipsilaterally innervated by the pudendal nerve.     

A histochemical and immunohistochemical study of the autonomic innervation of the lower urinary tract of the female pig. Is the pig a good model for the human bladder and urethra?

The detrusor muscle, bladder neck, proximal, middle and distal regions of the urethra of the female pig were studied by histochemical and immunohistochemical methods to localize catecholamine-containing, acetylcholinesterase-positive and peptide-containing nerves. The peptides examined included: vasoactive intestinal polypeptide, substance P, somatostatin, [Met]enkephalin, bombesin and gastrin. The greatest density of nerves was found in the smooth muscle of the distal urethra, followed by the bladder neck, middle urethra, and proximal urethra, with the least in the detrusor muscle. The greatest number of nerve fibres stained for acetylcholinesterase, followed by vasoactive intestinal polypeptide- and catecholamine-containing fibres. Substance P-immunoreactive nerve fibres were confined to the bladder neck and distal urethral regions. [Met]enkephalin-and gastrin-immunoreactive nerves were most dense in the distal urethra but absent in detrusor muscle, while somatostatin-immunoreactive nerve fibres were sparsely distributed throughout the lower urinary tract. No nerve fibres showing immunoreactivity to bombesin were found. Catecholamine-containing, acetylcholinesterase-positive, vasoactive intestinal polypeptide-, substance P-, [Met]enkephalin- and gastrin-immunoreactive nerves were also found on the adventitial-medial border of blood vessels in the pig urinary tract. In the intrinsic external urethral sphincter, located in the distal urethra, vasoactive intestinal polypeptide- and gastrin-immunoreactive nerve fibres were found bordering a small number of individual striated muscle fibres, while catecholamine-containing nerves were found predominantly in the connective tissue surrounding the striated muscle fibres. Dense populations of acetylcholinesterase-positive nerve fibres were found associated with the striated muscle fibres, with end plates on some of them. Intramural ganglia, composed of two to 30 neurones, were found in the bladder neck and middle and distal regions of the urethra. In the smooth muscle, and in the vicinity of the striated muscle regions of the intrinsic external urethral sphincter, there were small ganglia, containing two to three neurones, which were vasoactive intestinal polypeptide-, [Met]enkephalin- and somatostatin-immunoreactive. The results are compared to the autonomic innervation of the human bladder and urethra as previously described and it is concluded that the lower urinary tract of the pig is a good model for some features of the lower urinary tract of man, but a poor model for others.     

Contractile properties of urethral smooth muscles of young and aged female dogs: Morphological and pharmacological aspects

BACKGROUND: Alpha1-adrenoceptors are highly concentrated in the urethral smooth muscles and may play an important role in the contraction of this area. However, detailed examinations of age-related changes of the properties of urethral smooth muscle have rarely been undertaken. METHODS: The contractile properties of urethras from young non-parous and old parous female beagles were determined with a urethral function study, macroscopic autoradiography for urethras using [3H]-labeled tamsulosin and morphometry of the urethral muscles. RESULTS: The antagonistic effect (pA2) of prazosin for norepinephrine was 7.76+/-0.13 in young dogs and 7.62+/-0.06 in aged dogs. The specific binding of [3H]-tamsulosin (a relatively selective alpha1A-adrenoceptor antagonist) was recognized diffusely in proximal urethras with in vitro autoradiography. The density of binding in smooth muscles was approximately 60 and 40% in circular longitudinal layers, respectively, for both dogs. CONCLUSIONS: The female canine urethra had alpha1A, and alpha1L-adrenoceptors. No age-related changes were seen in the function of the proximal urethra, distribution of alpha1-adrenoceptor binding sites and smooth muscle densities.     

Urethral pressure variations in women with neurourological symptoms: II. Relationship to urethral smooth muscle

Simultaneous urethrocystometry and electromyography from the urethral striated muscle during bladder filling was performed on female patients complaining of neurourological symptoms. Their maximum urethral pressure varied between 20 and 84 cm H₂O. To study the effect of the urethral smooth muscle on the urethral pressure variations, a bilateral pudendal block was applied successfully in 12 patients. It was found that in 1 patient the urethral pressure variations were caused by the urethral striated muscle only, in 4 patients they were caused mainly by the urethral striated muscle, in 2 other patients they were caused equally by urethral striated and smooth muscle, and finally in 5 patients mainly by urethral smooth muscle. By eliminating the urethral striated muscle activity by pudendal block the maximum urethral pressure was reduced 20 to 84%.     

电刺激治疗仪治疗女性尿失禁81例

目的 探讨电刺激治疗仪在女性尿失禁治疗中的作用机制及疗效。方法 应用置于阴道内的电极探头,在不同的电流状态下,间歇刺激阴部神经,达到抑制逼尿肌收缩、增加尿道阻力,从而控制尿液渗漏,采用此法治疗81例不同程度的尿失禁患者。结果 尿失禁患者渗、漏尿事件减少47.5％,尿频次数减少46％,24h内排尿次数在10～12次之间;患者的整体的主观改善率为66％,整体的客观改善率为74.5％。结论 电刺激治疗仪在女性尿失禁治疗有明显疗效,可提高患者的生活质量。     

Effects of selective autonomic and pudendal denervation on the urethral function and development of retention in female dogs

PURPOSE: This trial is an experimental approach to the possible causes of continence and voiding problems after urethra sparing radical cystectomy and orthotopic bladder substitution in women. MATERIALS AND METHODS: Between January 1996 and January 1999 we included 24 mongrel female dogs in this 4-phase study of 6 dogs each. The effects of autonomic denervation of the urethra (phase 1) and urethral transection just distal to the bladder neck (phase 2) on the urethral pressure profile were recorded. In phase 3 the effects of autonomic denervation, urethral transection and pharmacological manipulation of the denervated transected urethra on the urethral pressure profile were studied in succession. In phase 4 the effects of pudendal nerve transection and pharmacological blockade were recorded. In the 12 phases 2 and 3 dogs the transected urethra was re-anastomosed to the bladder neck. Acute experiments were repeated after 2 and 6 months, urethrocystoscopy was done and post-void residual urine was estimated. Two of the latter dogs were sacrificed 6 months after the acute experiment and the urethras were histopathologically examined. RESULTS: Autonomic denervation resulted in a 46% to 48% decrease in mean maximal pressure in the proximal urethra in phases 1 and 3 (p <0.001) with no significant effect on the distal urethra. Urethral transection in phase 2 did not affect the urethral pressure profile. Phentolamine injection after urethral denervation and transection in phase 3 produced a further reduction of 11.3% and 46.3% in mean resting pressure in the proximal and distal urethra, respectively, while succinyl choline produced a 38.1% further decrease in the distal urethra. Unilateral and bilateral pudendal denervation reduced pressure in the distal urethra significantly but not in the proximal urethra. When phentolamine was given thereafter, a further decrease of 38% and 2.4% resulted in resting pressure values in the proximal and distal urethra, respectively. The change in distal urethral pressure was marginally significant after succinyl choline injection (p = 0.05). Results were reproducible after 2 and 6 months. The proximal urethra remained patent with no post-void residual urine after autonomic denervation. There was no significant urethral fibrosis after realignment of the transected urethra in the 2 sacrificed phases 2 and 3 dogs. CONCLUSIONS: From this study we concluded that autonomic denervation reduced pressure in the proximal urethra by less than 50%. Continuity of the urethra with the bladder is not necessary for proper urethral function. After autonomic denervation the proximal urethra remained patent with no subsequent fibrosis. In addition, no post-void residual urine was noted. Bilateral pudendal denervation did not completely block activity of the distal urethra. The nonneuromuscular components had a small role in the creation of urethral closure function.     

Vasoactive intestinal polypeptide-, somatostatin- and substance P-immunoreactive nerves in the smooth and striated muscle of the intrinsic external urethral sphincter of patients with spinal cord injury

Specimens obtained by transurethral sphincterectomy from patients with spinal cord injury and carcinoma of the bladder were studied immunohistochemically. In the smooth muscle region of the sphincter, vasoactive intestinal polypeptide-, substance P- and somatostatin-immunoreactive fluorescent, varicose nerve fibers were seen. In the striated muscle region, VIP-immunoreactive nerves were found around striated muscle fibers and bundles, while somatostatin- and substance P-immunoreactive nerves were confined to nerve bundles. In both the smooth and striated muscle regions of the intrinsic external urethral sphincter, VIP-immunoreactive nerves were seen around blood vessels. No differences were observed in the immunohistochemical localization of these peptide-containing nerves in the two groups of patients. No immunofluorescence for [Met]enkephalin, bombesin, neurotensin or serotonin was found in any nerves in the urethra.     

Perineal nerve damage in genuine stress urinary incontinence. An electrophysiological study

Twelve patients with genuine stress incontinence of urine were investigated using manometric and electrophysiological techniques. All were shown to have slowed conduction in the perineal branch of the pudendal nerve which innervates the periurethral striated sphincter muscle. The mean perineal nerve terminal motor latency in these patients was 3.9 +/- 0.8 (ms) and in 20 age and parity matched control subjects was 2.0 +/- 0.2 (ms) (P less than 0.001). These results are consistent with a neurogenic factor in patients with genuine stress incontinence of urine which may have implications regarding selection of patients for surgery to restore urethral competence.