External Urethral Sphincter Relaxation Research Articles

An innovative electrical neurostimulation approach to mimic reflexive urination control in spinal cord injury models

Neurogenic lower urinary tract dysfunction (NLUTD) is a frequent consequence of spinal cord injury (SCI), leading to symptoms that significantly impact quality of life. Although many life-saving techniques are available, current treatment strategies for managing NLUTD still exhibit limitations and drawbacks. Here, we introduce a new electrical neuromodulation strategy involving electrical stimulation of the major pelvic ganglion (MPG) to initiate bladder contraction, in conjunction with innovative programmable (IPG) electrical stimulation on the pudendal nerve (PN) to induce external urethral sphincter (EUS) relaxation in freely moving or anesthetized SCI mice. Furthermore, we conducted the void spot assay, and cystometry coupled with EUS electromyography (EMG) recordings to evaluate voiding function, and monitor bladder pressure and EUS activity. Our findings demonstrate that our novel electrical neuromodulation approach effectively triggers coordinated bladder muscle contraction and EUS relaxation, effectively counteracting SCI-induced NLUTD. Additionally, this electrical neuromodulation method enhances voiding efficiency, closely resembling natural reflexive urination in SCI mice. Thus, our study offers a promising electrical neurostimulation approach aimed at restoring physiological coordination and potentially offering personalized treatment for improving voiding efficiency in individuals with SCI-associated NLUTD.

High Prevalence of Psychological Comorbidities and Functional Neurological Symptoms in Women With Urinary Retention.

Chronic idiopathic urinary retention (CIUR) in young women is poorly understood and a probable etiology is established only in around 40%, most commonly a primary disorder of external urethral sphincter relaxation, sometimes referred to as Fowler's syndrome. A high prevalence of psychological and functional comorbidities is reported, however these have been poorly characterized. Women consecutively referred for the assessment and management of CIUR were evaluated cross-sectionally for 13 psychological/behavioral domains using a structured clinical interview: depression, anxiety, post-traumatic stress disorder (PTSD), other psychiatric history, functional neurological disorder, other functional syndromes, childhood and adult trauma, personality disorder, and self-harm (ever/current). A total of 91 women (mean age [SD]: 34 [11] years) were evaluated. Women with Fowler's syndrome (n = 69) were younger (mean age [SD]: 32 [9] vs 40 [13] years) than women without Fowler's syndrome and reported shorter mean duration of urinary symptoms (mean [SD]: 5 [6] vs 10 [9]). A high prevalence of psychiatric and psychological comorbidities was reported (97%) including current depression (77%), current anxiety (78%), and PTSD (32%). A high prevalence of functional neurological disorder (56%) and other functional symptoms (65%) was also reported. Self-harm was reported in (14%) and personality disorder in 16%. Childhood trauma was reported in 35% of women. Young women with CIUR report a high burden of psychiatric disorders, affective symptoms, trauma, PTSD, self-harm, and functional neurological disorder, particularly in those with Fowler's syndrome. These factors can undermine the engagement with health care professionals and affect management and should therefore be addressed during the urological assessment.

Sex differences in lower urinary tract function in mice with or without spinal cord injury.

We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). SCI was induced by Th8-9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6-S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme-linked immunosorbent assay. Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6-S1 DRG and NGF in the bladder could be involved in SCI-induced lower urinary tract dysfunction in both sexes of mice.

MP60-08 COMPARISON OF LOWER URINARY TRACT DYSFUNCTION AFTER SPINAL CORD INJURY (SCI) BETWEEN FEMALE AND MALE MICE

You have accessJournal of UrologyCME1 Apr 2023MP60-08 COMPARISON OF LOWER URINARY TRACT DYSFUNCTION AFTER SPINAL CORD INJURY (SCI) BETWEEN FEMALE AND MALE MICE Mamoru Hashimoto, Kang Jun Cho, Stephanie L Daugherty, PA Pittsburgh, Nobutaka Shimizu, Pradeep Tyagi, Akihide Hirayama, Hirotsugu Uemura, Jonathan M Beckel, Sergei Karnup, and Naoki Yoshimura Mamoru HashimotoMamoru Hashimoto More articles by this author , Kang Jun ChoKang Jun Cho More articles by this author , Stephanie L DaughertyStephanie L Daugherty More articles by this author , PA PittsburghPA Pittsburgh More articles by this author , Nobutaka ShimizuNobutaka Shimizu More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Akihide HirayamaAkihide Hirayama More articles by this author , Hirotsugu UemuraHirotsugu Uemura More articles by this author , Jonathan M BeckelJonathan M Beckel More articles by this author , Sergei KarnupSergei Karnup More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003318.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In humans, voiding occurs during synergic relaxation of the external urethral sphincter (EUS), and SCI induces detrusor-sphincter dyssynergia (DSD) shown by tonic EUS contraction during voiding. However, EUS bursting activity is known to be an important mechanism for efficient voiding in spinal intact (SI) and SCI rats while such data are less available in mice. Thus, we evaluated gender-specific EUS function during voiding in male and female mice with or without SCI. METHODS: C57BL/6N mice at 9-10-weeks old were used. SCI mice underwent complete transection of the Th8-9 spinal cord. Six weeks after SCI, cystometrograms (CMGs) and EUS- electromyography (EMG) were performed under an awake condition. Thereafter, L6-S1 dorsal root ganglia (DRG) were harvested to evaluate the transcripts of TRPV1 and Piezo2 using qPCR. RESULTS: In female SI mice, voiding occurred during an EUS relaxation period. Female SCI mice voided urine during notch like reductions in bladder pressure, which corresponded to EMG signal reduction periods during tonic EMG activity (DSD). On the other hand, male SI and SCI mice voided during EUS bursting activity characterized by alternating active and silent phases of EMG activity, with the longer active phase and low voiding efficiency in SCI vs. SI mice (Table and Figure). The mRNA levels of TRPV1 and Piezo2 in L6-S1 DRG were significantly higher in SCI male mice (n=4) and female mice (n=4) vs. SI mice (n=4). CONCLUSIONS: Lower urinary tract function during the voiding phase was different between male and female mice. Female SI mice, in which voiding occurs during EUS relaxation, and female SCI mice, which exhibit DSD with periodic EUS relaxations, seem to be more suitable for the study of SCI-induced EUS dysfunction in humans, compared to SI and SCI male mice that exhibit EUS bursting activity during voiding. Source of Funding: NIH R01DK129194 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e846 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mamoru Hashimoto More articles by this author Kang Jun Cho More articles by this author Stephanie L Daugherty More articles by this author PA Pittsburgh More articles by this author Nobutaka Shimizu More articles by this author Pradeep Tyagi More articles by this author Akihide Hirayama More articles by this author Hirotsugu Uemura More articles by this author Jonathan M Beckel More articles by this author Sergei Karnup More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF downloadLoading ...

Spinal interneurons of the lower urinary tract circuits.

The storage and elimination of urine requires coordinated activity between muscles of the bladder and the urethra. This coordination is orchestrated by a complex system containing spinal, midbrain and forebrain networks. Normally there is a reciprocity between patterns of activity in urinary bladder sacral parasympathetic efferents and somatic motoneurons innervating the striatal external urethral sphincter muscle. At the spinal level this reciprocity is mediated by ensembles of excitatory and inhibitory interneurons located in the lumbar-sacral segments. In this review I will present an overview of currently identified spinal interneurons and circuits relevant to the lower urinary tract and will discuss their established or hypothetical roles in the cycle of micturition. In addition, a recently discovered auxiliary spinal neuronal ensemble named lumbar spinal coordinating center will be described. Sexual dimorphism and developmental features of the lower urinary tract which may play a significant role in designing treatments for patients with urine storage and voiding dysfunctions are also considered. Spinal cord injuries seriously damage or even eliminate the ability to urinate. Treatment of this abnormality requires detailed knowledge of supporting neural mechanisms, therefore various experiments in normal and spinalized animals will be discussed. Finally, a possible intraspinal mechanism will be proposed for organization of external urethral sphincter (EUS) bursting which represents a form of intermittent EUS relaxation in rats and mice.

Spinal cord stimulation ameliorates detrusor over-activity and visceromotor pain responses in rats with cystitis.

Interstitial cystitis/painful bladder syndrome/(IC/PBS) results in recurring pain in the bladder and surrounding pelvic region caused by abnormal excitability of micturition reflexes. Spinal cord stimulation (SCS) is currently clinically used for the attenuation of neuropathic and visceral pain. The present study examined whether SCS at upper lumbar segments modulates detrusor overactivity and visceral hyperalgesia associated with cystitis in a rat model of cyclophosphamide (CYP)-induced cystitis. Cystitis was induced by intraperitoneal injection of CYP (200 mg/kg) in six adult female Sprague Dawley rats 48 h prior to urodynamic recordings. Another six rats served as-controls with saline injection. Cystometry and the external urethral sphincter (EUS) electromyography during bladder infusion were evaluated under urethane anesthesia. The visceromotor reflexes (VMR) obtained from the external abdominal oblique muscle were quantified during bladder infusion and isotonic bladder distension (IBD), respectively. After baseline recordings were taken, SCS was applied on the dorsal surface of L3 for 25 min. Urodynamic recordings and VMR during bladder infusion and IBD were repeated 2 h after SCS. CYP resulted in detrusor overactivity, stronger EUS tonic contractions, and increased VMR. SCS significantly reduced non-voiding contractions, prolonged EUS relaxation, and delayed VMR appearance during bladder infusion as well as significantly decreased VMR during IBD in cystitis rats. SCS improved bladder function and EUS relaxation during bladder infusion and significantly attenuated visceral nociceptive-related VMR during IBD in cystitis rats. SCS may have therapeutic potential for patients with hyperalgesia and IC/PBS.

The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice.

We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 wk after SCI. Female C57BL/6N mice were divided into four groups: 1) spinal intact (SI)-control, 2) SI-capsaicin pretreatment (Cap), 3) SCI-control, and 4) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition. In the Cap groups, capsaicin (25, 50, or 100 mg/kg) was injected subcutaneously 4 days before the experiments. In the SI-Cap group, 100 mg/kg capsaicin pretreatment significantly increased bladder capacity and decreased the silent period duration of EUS/EMG compared with the SI-control group. In the SCI-Cap group, 50 and 100 mg/kg capsaicin pretreatment decreased the number of nonvoiding contractions (NVCs) and the duration of reduced EUS activity during voiding, respectively, compared with the SCI-control group. In SCI mice, hexamethonium, a ganglionic blocker, almost completely blocked NVCs, suggesting that they are of neurogenic origin. Patch-clamp recordings in capsaicin-sensitive bladder afferent neurons from SCI mice showed hyperexcitability, which was evidenced by decreased spike thresholds and increased firing rate compared with SI mice. These results indicate that capsaicin-sensitive C-fiber afferent pathways, which become hyperexcitable after SCI, can modulate bladder and urethral sphincter activity in awake SI and SCI mice. Detrusor overactivity as shown by NVCs in SCI mice is significantly but partially dependent on capsaicin-sensitive C-fiber afferents, whereas the EUS relaxation during voiding is enhanced by capsaicin-sensitive C-fiber bladder afferents in SI and SCI mice.

Phasic activation of the external urethral sphincter increases voiding efficiency in the rat and the cat

ObjectiveElectrical stimulation of the pudendal nerve (PN) is a potential therapy for bladder dysfunction, but voiding efficiency (VE) produced by PN stimulation appears limited to 60–70%. We conducted experiments in rats and cats to investigate the hypothesis that introduction of artificial phasic bursting activity of the external urethral sphincter (EUS) would enhance VE under conditions where such activity was absent. Materials and methodsCystometry experiments were conducted in 17 urethane anesthetized female Sprague-Dawley rats and 4 α-chloralose anesthetized male cats. The effects of phasic stimulation of the pudendal motor branch on VE were quantified in intact conditions, following bilateral transection of the motor branch of the PN, and following subsequent bilateral transection of the sensory branch of the PN. ResultsArtificial phasic bursting activity in the EUS generated by electrical stimulation of the motor branch of the PN increased VE in both rats and cats. Subsequent transection of the sensory branch of the PN abolished the increased VE elicited by phasic stimulation in both rats and cats. ConclusionsArtificial phasic EUS bursting restored efficient voiding in rats. Introduction of artificial phasic bursting in cats, which normally exhibit EUS relaxation while voiding, was also effective in promoting efficient voiding. In both species phasic EUS activity increased voiding efficiency via activation of pudendal sensory pathways. These results provide further insight into the function of phasic EUS activity in efficient voiding and highlight a novel approach to increase VE generated by pudendal afferent nerve stimulation.

Contribution of the external urethral sphincter to urinary void size in unanesthetized unrestrained rats.

In anesthetized rats, voiding is typically associated with phasic activation (bursting) of the external urethral sphincter (EUS). During spontaneous voiding in unanesthetized, unrestrained rats, EUS bursting is the most common form of EUS activity exhibited, but it is not necessary for productive voiding to occur. The aim of the present study was to determine which aspects of EUS activity contributed to void size during bursting and non-bursting voiding in conscious, freely moving rats. Female rats were implanted with electrodes adjacent to the EUS for recording electromyographic activity (EMG). EUS EMG recordings were performed during 24-hr sessions in a metabolic cage while voided urine was continuously collected and weighed. Void size was positively correlated with the duration of the intra-burst silent and active periods and variables reflecting the overall intensity and duration of bursting, particularly at lower frequencies within the 3-10 Hz range of EUS bursting. In addition, void size was inversely related to the frequency of bursting and to the average EMG amplitude during voiding, both in voids with and without bursting. EUS bursting contributes to productive voiding when bursting is present. Lower bursting frequencies elicit more productive voiding than do higher frequencies. In the absence of bursting, the association of increased void size with smaller average EUS EMG amplitude suggests that conscious rats can perform synergic voiding (i.e., bladder contraction with EUS relaxation) that is comparable to that seen in humans and other typically non-bursting species. Neurourol. Urodynam. 35:696-702, 2016. © 2015 Wiley Periodicals, Inc.

Spinal stimulation of the upper lumbar spinal cord modulates urethral sphincter activity in rats after spinal cord injury.

After spinal cord injury (SCI), the neurogenic bladder is observed to develop asynchronous bladder and external urethral sphincter (EUS) contractions in a condition known as detrusor-sphincter dyssnergia (DSD). Activation of the EUS spinal controlling center located at the upper lumbar spinal cord may contribute to reduce EUS dyssynergic contractions and decrease urethral resistance during voiding. However, this mechanism has not been well studied. This study aimed at evaluating the effects of epidural stimulation (EpS) over the spinal EUS controlling center (L3) in combination with a serotonergic receptor agonist on EUS relaxation in naive rats and chronic (6-8 wk) T8 SCI rats. Cystometrogram and EUS electromyography (EMG) were obtained before and after the intravenous administration of 5HT-1A receptor agonist and antagonist. The latency, duration, frequency, amplitude, and area under curve of EpS-evoked EUS EMG responses were analyzed. EpS on L3 evoked an inhibition of EUS tonic contraction and an excitation of EUS intermittent bursting/relaxation correlating with urine expulsion in intact rats. Combined with a 5HT-1A receptor agonist, EpS on L3 evoked a similar effect in chronic T8 SCI rats to reduce urethral contraction (resistance). This study examined the effect of facilitating the EUS spinal controlling center to switch between urine storage and voiding phases by using EpS and a serotonergic receptor agonist. This novel approach of applying EpS on the EUS controlling center modulates EUS contraction and relaxation as well as reduces urethral resistance during voiding in chronic SCI rats with DSD.

THE USE OF BOTULINUM TOXIN IN WOMEN WITH FOWLER'S SYNDROME

<h3>Background</h3> Urinary retention in young women due to a disorder of external urethral sphincter relaxation, known as Fowler9s syndrome, is characterised by elevated urethral pressure profile (UPP) and abnormal urethral sphincter EMG. Sacral neuromodulation is the only effective treatment currently. The aim of this study was to assess the efficacy of botulinum toxin in Fowler9s Syndrome. <h3>Methods</h3> Ten women with Fowler9s Syndrome (obstructed voiding (n=5), complete urinary retention (n=5) were recruited at a tertiary referral centre. Baseline and post-treatment symptoms were assessed using the International Prostate Symptom Score (IPSS) questionnaire, and urinary flow and post-void residual volumes were measured. Patients were reviewed at weeks 1, 4 and 10 post-treatment. <h3>Results</h3> There was a significant improvement in symptom scores on the IPSS questionnaire at week 10. In women with obstructed voiding, mean flow rate improved from 8.12mls/sec (3–10) to 12.6mls/sec (6–27), whereas four women in complete retention voided spontaneously. Mean post-void residual volume decreased from 315mls (40–700) to 112 mls (0–230). No serious side effects were reported. <h3>Conclusion</h3> In this pilot study, urethral sphincter injections of Botulinum toxin was shown to be safe and effective in the management of urinary retention in women due to Fowler9s syndrome.

The ameliorating effect of dantrolene on the morphology of urinary bladder in spinal cord injured rats

In animal models of spinal cord injury (SCI), the urinary bladder can undergo significant structural and physiological alterations. Dantrolene has been shown to be neuroprotective by reducing neuronal apoptosis after SCI. Furthermore, in addition to its anti-inflammatory and antioxidant properties, it appears to have a beneficial action on voiding, once this drug acts on the external urethral sphincter relaxation. In the present study, we investigated the effects of dantrolene on urinary bladder injury that follows experimental SCI. Forty-six male Wistar rats were laminectomized at T13, and a compressive trauma was performed to induce SCI. After euthanasia, the urinary bladder was removed for gross and histological evaluation. Traumatized animals showed urinary retention with severe hemorrhagic cystitis. Injured animals treated with dantrolene had less bladder hemorrhage and inflammatory infiltrate than those treated with placebo ( p < 0.05). Our results demonstrate that dantrolene may protect against urinary bladder lesions that follow SCI. Treating spinal cord-injured patients with this agent may be a promising additional therapeutic strategy to alleviate the accompanying inflammatory process. The results of the current study show that dantrolene has protective effects on spinal cord contusion-induced urinary bladder injury. The impaired integrity of bladder morphology was ameliorated by dantrolene treatment.

Intraspinal stimulation for bladder voiding in cats before and after chronic spinal cord injury

The long-term objective of this study is to develop neural prostheses for people with spinal cord injuries who are unable to voluntarily control their bladder. This feasibility study was performed in 22 adult cats. We implanted an array of microelectrodes into locations in the sacral spinal cord that are involved in the control of micturition reflexes. The effect of microelectrode stimulation was studied under light Propofol anesthesia at monthly intervals for up to 14 months. We found that electrical stimulation in the sacral parasympathetic nucleus at S2 level or in adjacent ventrolateral white matter produced bladder contractions insufficient for inducing voiding, while stimulation at or immediately dorsal to the dorsal gray commissure at S1 level produced strong (at least 20 mmHg) bladder contractions as well as strong (at least 40 mm Hg) external urethral sphincter relaxation, resulting in bladder voiding in 14 animals. In a subset of three animals, spinal cord transection was performed. For several months after the transection, intraspinal stimulation continued to be similarly or even more effective in inducing the bladder voiding as before the transection. We speculate that in the absence of the supraspinal connections, the plasticity in the local spinal circuitry played a role in the improved responsiveness to intraspinal stimulation.

Activation of the external urethral sphincter central pattern generator by a 5-HT1A receptor agonist in rats with chronic spinal cord injury

We recently demonstrated that treatment with the 5-HT(1A/7) receptor agonist [(R)-(+)-8-hydroxy-2-di-n-propylamino]tetralin (8-OH-DPAT) increases bladder capacity in chloralose-anesthetized female cats with chronic spinal cord injury. In the current study, we investigated the effects of 8-OH-DPAT on bladder capacity and external urethral sphincter (EUS) activity in urethane-anesthetized female rats (initial body mass 175-200 g) with chronic spinal cord injury (transsection at T10). Cystometric study took place 8-12 wk posttranssection. Intravesical pressure was monitored in urethane-anesthetized rats with a transvesical catheter, and EUS activity was assessed electromyographically. Spinal cord injury disrupts phasic activity of the EUS, resulting in decreased voiding efficiency and increased residual volume. 8-OH-DPAT induced a dose-dependent decrease in bladder capacity (the opposite of its effect in chronic spinal cord-injured cats) with an increase in micturition volume and decrease in residual volume resulting from improvement in voiding efficiency. The unexpected improvement in voiding efficiency can be explained by the 8-OH-DPAT-induced emergence of phasic EUS relaxation. Phasic EUS relaxation was also altered by 8-OH-DPAT in spinally intact rats, whereas the 5-HT(1A) receptor antagonist N-tert-butyl-3-[4-(2-methoxyphenyl)-piperazin-1-yl]-2-phenylpropanamide (WAY-100635), on its own, was without effect. It remains to be determined when phasic relaxation is restored after spinal cord injury, and indeed whether it is ever truly lost or is only temporarily separated from excitatory input.

Barrington's nucleus in the guinea pig (Cavia porcellus): Location in relation to noradrenergic cell groups and connections to the lumbosacral spinal cord

Micturition is largely controlled by Barrington's nucleus in the dorsolateral tegmentum of the pons. This nucleus coordinates simultaneous bladder contraction and external urethral sphincter relaxation, by means of a specific pattern of projections to the lumbosacral spinal cord. The most widely used small animal model in neurourological research is the rat. However, urodynamic studies suggest that, in sharp comparison to rat, guinea pig micturition is very similar to human micturition. Therefore, the present study, using retrograde and anterograde tracing and double immunofluorescence, was designed to investigate the location of Barrington's nucleus in the guinea pig, to identify Barrington's nucleus projections to the spinal cord and to clarify the relationship of Barrington's nucleus to pontine noradrenergic cell groups. Results show that Barrington's nucleus is located in the dorsolateral pons, projects to the intermediolateral and intermediomedial cell groups of the lumbosacral spinal cord and is clearly distinct from the pontine noradrenergic cell groups. These results show that the neuroanatomical circuitry in the spinal cord and brainstem that controls micturition in the guinea pig is similar to that in rat. This means that the differences between rat and guinea pig micturition on a behavioral level are not the result of different neuroanatomical connections in these parts of the central nervous system. These results provide a neuroanatomical basis for further neurourological studies in guinea pig.

Passive Biaxial Mechanical Properties of the Rat Bladder Wall After Spinal Cord Injury

Changes in the mechanical properties of the bladder wall after spinal cord injury can alter bladder compliance and wall tension, leading to changes in afferent nerve activity and to abnormal reflex mechanisms. To our knowledge we report the first application of biaxial mechanical testing to the normal bladder wall and demonstrate how these properties change after spinal cord injury. Whole bladders were harvested from mature female Sprague-Dawley rats weighing 250 to 300 gm. Test group animals underwent complete spinal cord transection at the T9 to T10 level and normal animals comprised the control group. The bladders were cut open longitudinally, the trigone and apex were removed and the remaining tissue was trimmed to a square of 9 to 13 mm. per side. Mechanical properties of the tissue sample were tested using planar biaxial testing, in which a stress was applied in the circumferential and longitudinal (base-apex) directions, and resulting axial strains were measured. In normal and spinal cord injured rats bladder wall tissue demonstrated isotropic mechanical behavior when equal stress levels were applied in anatomical directions. However, under nonequi-biaxial loading bladder specimens were not truly isotropic but displayed anisotropic-like behavior. Spinal cord injured tissues were consistently more compliant than normal controls. Biaxial mechanical testing can detect differences in normal control and hypertrophied rat bladders 10 and 14 days after spinal cord injury. These changes represent an important component of the bladder response to spinal cord injury.

Influences of external urethral sphincter relaxation induced by alpha-bungarotoxin, a neuromuscular junction blocking agent, on voiding dysfunction in the rat with spinal cord injury

Objectives. To determine whether external urethral sphincter (EUS) relaxation induced by alpha-bungarotoxin, a highly selective neuromuscular junction blocking agent, could ameliorate voiding dysfunction after spinal cord injury (SCI) in rats. Methods. The effects of intravenous alpha-bungarotoxin (333 μg/kg) were evaluated during cystometry in decerebrate, unanesthetized female Sprague-Dawley rats (250 to 300 g) with spinal cords chronically transected at T7-9 (n = 7) or with normal spinal cords (NSC) (n = 7). Parameters measured included voided volume (VV), residual volume (RV), volume threshold for inducing micturition (VT), voiding efficiency (VE), micturition pressure (MP), pressure threshold for inducing micturition (PT), bladder contraction duration (BCD), and compliance (CP). Results. In SCI rats, treatment with alpha-bungarotoxin improved voiding. The toxin increased VE (31%) and reduced RV (42%), MP (52%), BCD (14%), and VT (31%). VV, PT, and CP were not altered. In NSC rats, alpha-bungarotoxin decreased VE (23%), increased RV (63%), and decreased MP (36%), VV (38%), and VT (20%) but did not change BCD and CP. Conclusions. The results of our study demonstrated that alpha-bungarotoxin improved voiding in SCI rats by reducing urethral outlet resistance. However, in NSC rats, the toxin reduced voiding, probably by suppressing high-frequency phasic sphincter activity, necessary for efficient urine elimination in normal animals. The present results provide further support for the view that drugs that depress striated muscle activity can be useful in the treatment of voiding dysfunction after SCI.

Urodynamic dysfunction in infants with vesicoureteral reflux

Vesicoureteral reflux (VUR) may result from inadequate length of the intravesical ureteric tunnel and from urodynamic dysfunction. VUR and symptomatic urinary tract infection (UTI) are both more common in male infants and may be related to urodynamic dysfunction and functional intravesical obstruction. We therefore conducted urodynamic studies in 75 infants with primary VUR and retrospectively evaluated their voiding cystourethrogram (VCUG) for evidence of inadequate sphincteric relaxation. High voiding detrusor pressure (>70 cm H(2)O), increased postvoid residual (>2 mL/kg body weight), or detrusor-sphincter dyssynergy were observed in 79% of infants with primary VUR without significant differences between male and female infants or in infants with or without UTI. Infants with bilateral grade IV-V VUR showed a higher prevalence of detrusor hyper-reflexia and higher voiding detrusor pressure than infants with lower grades of VUR or unilateral grade IV-V VUR. On VCUG, inadequate external urethral sphincter relaxation during voiding was noted in 10 of 47 male infants. The findings suggest that high intravesical pressures contribute to the development and severity of VUR, and that high voiding detrusor pressure in some infants with primary VUR may be related to inadequate relaxation of the external urethral sphincter.