External Urethral Sphincter Electromyogram Research Articles

Effects of low-intensity extracorporeal shock wave on bladder and urethral dysfunction in spinal cord injured rats.

To investigate the effects of low-intensity extracorporeal shock wave therapy (LiESWT) on bladder and urethral dysfunction with detrusor overactivity and detrusor sphincter dyssynergia (DSD) resulting from spinal cord injury (SCI). At 3 weeks after Th9 spinal cord transection, LiESWT was performed on the bladder and urethra of adult female Sprague Dawley rats with 300 shots of 2Hz and an energy flux density of 0.12mJ/mm2, repeated four times every 3 days, totaling 1200 shots. Six weeks postoperatively, a single cystometrogram (CMG) and an external urethral sphincter electromyogram (EUS-EMG) were simultaneously recorded in awake animals, followed by histological evaluation. Voiding efficiency significantly improved in the LiESWT group (71.2%) compared to that in the control group (51.8%). The reduced EUS activity ratio during voiding (duration of reduced EUS activity during voiding/EUS contraction duration with voiding + duration of reduced EUS activity during voiding) was significantly higher in the LiESWT group (66.9%) compared to the control group (46.3%). Immunohistochemical examination revealed that fibrosis in the urethral muscle layer was reduced, and S-100 stained-positive area, a Schwann cell marker, was significantly increased in the urethra of the LiESWT group. LiESWT targeting the urethra after SCI can restore the EUS-EMG tonic activity during voiding, thereby partially ameliorating DSD. Therefore, LiESWT is a promising approach for treating bladder and urethral dysfunction following SCI.

Therapeutic effects of a soluble guanylate cyclase activator, BAY 60-2770, on lower urinary tract dysfunction in mice with spinal cord injury.

We aimed to evaluate the effects of a soluble guanylate cyclase (sGC) activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury (SCI). Mice were divided into the following three groups: spinal cord intact (group A), SCI + vehicle (group B), and SCI + BAY 60-2770 (group C). SCI mice underwent Th8-Th9 spinal cord transection and treatment with BAY 60-2770 (10 mg/kg/day) once daily for 2-4 wk after SCI. We evaluated urodynamic parameters using awake cystometry and external urethral sphincter electromyograms (EMG); mRNA levels of mechanosensory channels, nitric oxide (NO)-, ischemia-, and inflammation-related markers in L6-S1 dorsal root ganglia, the urethra, and bladder tissues; and protein levels of cGMP in the urethra at 4 wk after SCI. With awake cystometry, nonvoiding contractions, postvoid residual, and bladder capacity were significantly larger in group B than in group C. Voiding efficiency (VE) was significantly higher in group C than in group B. In external urethral sphincter EMGs, the duration of notch-like reductions in intravesical pressure and reduced EMG activity time were significantly longer in group C than in group B. mRNA expression levels of transient receptor potential ankyrin 1, transient receptor potential vanilloid 1, acid-sensing ion channel (ASIC)1, ASIC2, ASIC3, and Piezo2 in the dorsal root ganglia, and hypoxia-inducible factor-1α, VEGF, and transforming growth factor-β1 in the bladder were significantly higher in group B than in groups A and C. mRNA levels of neuronal NO synthase, endothelial NO synthase, and sGCα1 and protein levels of cGMP in the urethra were significantly lower in group B than in groups A and C. sGC modulation might be useful for the treatment of SCI-related neurogenic lower urinary tract dysfunction.NEW & NOTEWORTHY This is the first report to evaluate the effects of a soluble guanylate cyclase activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury.

Beneficial effect of Bletilla striata extract solution on zymosan-induced interstitial cystitis in rat.

Interstitial cystitis (IC) is a chronic pain syndrome that is characterized by suprapubic pain upon bladder filling. Bletilla striata, a well-known traditional Chinese herb with established efficacy in wound healing and anti-inflammation, was hypothesized to improve the symptoms of IC possibly though forming a physical barrier that could isolate the bladder tissue from irritants. This study was conducted to evaluate the beneficial effects of intravesical treatment with B. striata extract solution (BSES) on visceral pain and bladder function of rats with zymosan-induced IC. Thirty female rats were randomly divided into control group, zymosan-induced cystitis rats treated with normal saline (Z + NS), and zymosan-induced cystitis rats treated with BSES (Z + BSES). All rats underwent evaluation for abdominal withdrawal reflex (AWR) scores to assess visceral hypersensitivity, cystometrography, and electromyogram (EMG) of both external urethral sphincter and bladder detrusor. Data were analyzed by one way analysis of variance. The Z + NS group had an increased visceral hypersensitivity as compared to control group. Rats treated with BSES (Z + BSES group) had decreased AWR scores and amplitude of bladder detrusor-EMG. Besides, BSES treatment improved overactive bladder with significant effects on the extend of micturition interval and increase of storage of urine. Intravesical instillation of BSES can significantly alleviate zymosan-induced visceral hypersensitivity and bladder overactivity associated with IC. This study suggested that intravesical instillation with BSES might be a promising treatment for IC.

Improvement of lower urinary tract function by a selective serotonin 5-HT1A receptor agonist, NLX-112, after chronic spinal cord injury

Spinal cord injury (SCI) above the lumbosacral level results in lower urinary tract dysfunction, including (1) detrusor hyperreflexia, wherein bladder compliance is low, and (2) a lack of external urethral sphincter (EUS) control, leading to detrusor-sphincter dyssynergia (DSD) with poor voiding efficiency. Experimental studies in animals have shown a dense innervation of serotonergic (5-HT) fibers and multiple 5-HT receptors in the spinal reflex circuits that control voiding function. Here, we investigated the efficacy of NLX-112 (a.k.a. befiradol or F13640), in regulating lower urinary tract function after T8 contusive SCI in rats. NLX-112 is a very potent, highly-selective, and fully efficacious 5-HT1A receptor agonist, which has been developed for the treatment of L-DOPA-induced dyskinesia in Parkinson's disease patients. We performed urodynamics tests and external urethral sphincter electromyogram recordings to assess lower urinary tract function while NLX-112 was infused through the femoral vein in rats with chronic complete SCI or contusive SCI. The dose response studies indicated that NLX-112 was able to improve voiding behavior by regulating both detrusor and EUS activity. These included improvements in voiding efficiency, reduction of detrusor hyperactivity, and phasic activity of EUS during the micturition period. In addition, the application of a selective 5-HT1A receptor antagonist, WAY100635, reversed the improved detrusor and EUS activity elicited by NLX-112. In summary, the current data suggest that pharmacological activation of 5-HT1A receptors by NLX-112 may constitute a novel therapeutic strategy to treat neurogenic bladder after SCI.

Effect of 5-HT2A receptor antagonist ketanserin on micturition in male rats

ObjectivesThis study aimed to investigate the effects of ketanserin on micturition mediated via the 5-HT2A receptor in the motoneuron nucleus of the Lumbosacral cord, as reflected in high frequency oscillations (HFOs) of intravesical pressure and the external urethral sphincter electromyogram (EUS-EMG) in anesthetized male rats. Methods：Male Sprague-Dawley rats were used. Cystometry and EUS-EMG were performed in all rats under urethane anesthesia to examine the variations after successive intrathecal (i.t.) administration of various doses of ketanserin into the lumbosacral cord. Immunofluorescence staining and Western blotting were made to observe the distribution of 5-HT2 A and −2C receptors in the lumbosacral cord motor neurons. ResultsCompared to the controls, ketanserin-treated rats showed a declined trend of dose-dependent manner in the HFOs, in accordance with the variation of EUS-EMG, while decreased micturition volume, voiding efficiency, and increased post-void residual volume was only observed at the dose of 0.1 mg/kg. The effects of ketanserin on the HFO and EUS-EMG activity were partially or completely reversed by the 5-HT2A/2C receptor agonist, DOI. Meanwhile, immunofluorescence staining and Western blot analysis showed that immunoreactivity of 5-HT2A receptor was higher than that of 5-HT2C, labeling in the lumbosacral cord motoneurons. ConclusionsThe intrathecally administrated 5-HT2A receptor antagonist ketanserin can weaken the EUS bursting activity, decrease HFOs, and reduce voiding efficiency as dose dependently. The effects of ketanserin on micturition may be mainly mediated via the 5-HT2A receptors in the motoneuron nucleus of the lumbosacral cord.

I-Tiao-Gung extract through its active component daidzin improves cyclophosphamide-induced bladder dysfunction in rat model.

We explored the therapeutic potential of intragastric administration traditional Chinese medicine Glycine tomentella Hayata (I-Tiao-Gung, ITG) extract and its active component Daidzin on cyclophosphamide (CYP)-induced cystitis and bladder hyperactivity in rats. Female Wistar rats were divided into control, CYP (200 mg/kg), CYP + ITG (1.17 g/kg/day), CYP + Daidzin (12.5 mg/kg/day), and 1 week of ITG preconditioning with CYP (ITG + CYP) groups. We determined the trans cystometrogram associated with external urethral sphincter electromyogram, and the expression of M2 and M3 muscarinic and P2 × 2 and P2 × 3 purinergic receptors by Western blot in these animals. ITG extract contains 1.07% of Daidzin and 0.77% of Daidzein by high-performance liquid chromatography. Daidzin was more efficient than Daidzein in scavenging H2 O2 activity by a chemiluminescence analyzer. CYP induced higher frequency, shorter intercontraction interval, lower maximal voiding pressure, lower threshold pressure, and Phase-2 emptying contraction with a depressed external urethral sphincter electromyogram activity, and hemorrhagic cystitis in the bladders. The altered parameters by CYP were significantly improved in CYP + ITG, CYP + Daidzin, and ITG + CYP groups. The P2 × 2 and P2 × 3 expressions were significantly upregulated in CYP group, but were depressed in CYP + ITG, CYP + Daidzin, and ITG + CYP groups. The M2 expression was not significantly different among these five groups. The M3 expression was significantly upregulated in CYP group, but was significantly depressed in CYP + ITG, CYP + Daidzin, and ITG + CYP groups. These data suggest that ITG extract through its active component Daidzin effectively improved CYP-induced cystitis by the action of restoring Phase 2 activity and inhibiting the expressions of P2 × 2, P2 × 3, and M3 receptors.

Relaxin-2 therapy reverses radiation-induced fibrosis and restores bladder function in mice.

To determine the efficacy of human relaxin-2 (hRLX2) in reversing radiation-induced bladder fibrosis and lower urinary tract dysfunction (LUTD). Radiation cystitis is a consequence of radiotherapy for pelvic malignancies. Acutely, irradiation leads to reactive oxygen/nitrogen species in urothelial cells, apoptosis, barrier disruption, and inflammation. Chronically, this results in collagen deposition, bladder fibrosis, and attenuated storage and voiding functions. In severe cases, cystectomies are performed as current therapies do not reverse fibrosis. We developed a mouse model for selective bladder irradiation (10 Gray; 1 Gy = 100 rads) resulting in chronic fibrosis within 6 weeks, with decreased bladder compliance, contractility, and overflow incontinence. Seven weeks post-irradiation, female C57Bl/6 mice were continuously infused with hRLX2 (400 μg/kg/day/14 days) or vehicle (saline) via subcutaneous osmotic pumps. Mice were evaluated in vivo using urine spot analysis, cystometrograms and external urethral sphincter electromyograms; and in vitro using length-tension measurements, Western blots, histology, and immunohistochemistry. hRLX2 reversed fibrosis, decreased collagen content, improved bladder wall architecture, and increased bladder compliance, detrusor smooth muscle Cav1.2 expression and detrusor contractility in mice with chronic radiation cystitis. hRLX2 treatment outcomes were likely caused by the activation of RXFP1/2 receptors which are expressed on the detrusor. hRLX2 may be a new therapeutic option for rescuing bladders with chronic radiation cystitis.

Targeting p75 neurotrophin receptors ameliorates spinal cord injury-induced detrusor sphincter dyssynergia in mice.

To determine the role of p75 neurotrophin receptor (p75NTR ) and the therapeutic effect of the selective small molecule p75NTR modulator, LM11A-31, in spinal cord injury (SCI) induced lower urinary tract dysfunction (LTUD) using a mouse model. Adult female T8 -T9 transected mice were gavaged daily with LM11A-31 (100 mg/kg) for up to 6 weeks, starting 1 day before, or 7 days following injury. Mice were evaluated in vivo using urine spot analysis, cystometrograms (CMGs), and external urethral sphincter (EUS) electromyograms (EMGs); and in vitro using histology, immunohistochemistry, and Western blot. Our studies confirm highest expression of p75NTRs in the detrusor layer of the mouse bladder and lamina II region of the dorsal horn of the lumbar-sacral (L6 -S1 ) spinal cord which significantly decreased following SCI. LM11A-31 prevented or ameliorated the detrusor sphincter dyssynergia (DSD) and detrusor overactivity (DO) in SCI mice, significantly improving bladder compliance. Furthermore, LM11A-31 treatment blocked the SCI-related urothelial damage and bladder wall remodeling. Drugs targeting p75NTRs can moderate DSD and DO in SCI mice, may identify pathophysiological mechanisms, and have therapeutic potential in SCI patients.

Prototype Deep Brain Stimulation System with Closed-Loop Control Feedback for Modulating Bladder Functions in Traumatic Brain Injured Animals

Traumatic brain injury (TBI) typically causes permanent brain tissue damage, which leads to permanent severe voiding dysfunction. Urinary retention is often refractory to standard therapies, and most patients require self-catheterization, which results in frequent urinary tract infections and reduces quality of life. Deep brain stimulation (DBS) might be a feasible alternative approach for treating bladder disorders in patients with TBI. In this study, we developed a DBS system with a closed-loop control strategy and determined the feasibility of this DBS system for improving bladder voiding function in a TBI animal model. A prototype of the DBS system was designed, fabricated and integrated with a closed-loop control algorithm based on the real-time external urethral sphincter-electromyogram feedback. A series of animal experiments was conducted to determine whether the feedback algorithm accurately detects the bladder status during cystometric measurements. Subsequent animal experiments were conducted to implement this DBS system and determine the performance of the closed-loop strategy for improving bladder functions in the TBI animal model. We successfully implemented a closed-loop algorithm for DBS control, and the accuracy of the bladder voiding phase detection was > 90%. Our system significantly improved the voiding efficiency in TBI rats from 22 to 74%. Although the prototype of the DBS feedback system was fabricated with surface-mounted device components and mounted on a 3D printed circuit board, the design principles and animal experience gathered from this research can serve as a basis for developing a new implantable bladder controller in the future.

Stimulation of the pelvic nerve increases bladder capacity in the prostaglandin E2 rat model of overactive bladder.

Overactive bladder (OAB) syndrome is a highly prevalent condition that may lead to medical complications and decreased quality of life. Emerging therapies focusing on selective electrical stimulation of peripheral nerves associated with lower urinary tract function may provide improved efficacy and reduced side effects compared with sacral neuromodulation for the treatment of OAB symptoms. Prior studies investigating the effects of pelvic nerve (PelN) stimulation on lower urinary tract function were focused on promoting bladder contractions, and it is unclear whether selective stimulation of the PelN would be beneficial for the treatment of OAB. Therefore our motivation was to test the hypothesis that PelN stimulation would increase bladder capacity in the prostaglandin E2 (PGE2) rat model of OAB. Cystometry experiments were conducted in 17 urethane-anesthetized female Sprague-Dawley rats. The effects of intravesical PGE2 vs. vehicle and PelN stimulation after intravesical PGE2 on cystometric parameters were quantified. Intravesical infusion of PGE2 resulted in decreased bladder capacity and increased voiding efficiency without a change in bladder contraction area under the curve, maximum contraction pressure, or contraction duration. Bladder capacity was also significantly decreased compared with vehicle (1% ethanol in saline) confirming that the change in bladder capacity was mediated by PGE2 PelN stimulation reversed the PGE2-induced change in bladder capacity and increased the external urethral sphincter electromyogram activity at a specific stimulation condition (amplitude of 1.0 times threshold at 10 Hz). These results confirm that the urodynamic changes reported in conscious rats are also observed under urethane anesthesia and that PelN stimulation is a novel and promising approach for the treatment of the symptoms of OAB.

Effect of orchiectomy and testosterone replacement on lower urinary tract function in anesthetized rats.

Lower urinary tract (LUT) symptoms (LUTS), including frequency, urgency, incomplete voiding, and slow stream, are common in both men and women with advancing age. The most common cause for LUTS in aging men is benign prostatic hyperplasia. Some studies have also revealed an inverse association of serum testosterone levels with LUTS; however, the underlying mechanisms by which gonadal hormones affect the LUT have not been clarified. In the present study, we examined the effect of orchiectomy and testosterone replacement on LUT function in adult male Sprague-Dawley rats. Six weeks after bilateral orchiectomy or sham operations and 3 wk after injection of long-acting testosterone undecanoate (100 mg/kg im), transvesical cystometry and external urethral sphincter electromyogram (EUS EMG) recordings were performed under urethane anesthesia. The micturition reflex was elicited in both sham and orchiectomized animals. In orchiectomized rats, volume threshold for inducing micturition decreased by 47.6%; however, contraction amplitude, duration, and voiding efficiency were similar in sham and orchiectomized rats. The active period during EUS EMG bursting was lengthened during micturition in orchiectomized animals. Testosterone treatment, which normalized plasma testosterone levels, reversed these changes but also increased the duration of EUS EMG bursting. Orchiectomy also reduced mean voiding flow rate estimated from the duration of EUS EMG bursting, an effect that was not reversed by testosterone. The results indicate that orchiectomy affects both the active and passive properties of the bladder and urethra, and that many, but not all, of the changes can be reversed by testosterone.

Chronic pudendal neuromodulation using an implantable microstimulator improves voiding function in diabetic rats

AbtractObjective. Few studies have investigated the feasibility of using chronic pudendal neuromodulation for improving voiding function in patients with diabetes who are also experiencing urinary retention. The present study investigated the effects of chronic electrical stimulation (ES) of the sensory branch of the pudendal nerve on voiding function in diabetic rats. Approach. A custom-made implantable microstimulation system was designed and manufactured for chronic implantation in normal control (NC) and diabetic rats. After three or six weeks of pudendal neuromodulation, the intravesical pressure, external urethral sphincter electromyograms (EUS-EMGs), and urine flow rate (UFR) of all rats were simultaneously recorded to assess the effects of chronic pudendal ES on voiding function. Morphological changes in pudendal axons were assessed through hematoxylin and eosin (H&E) staining. Results. Abnormal cystometric measurements, including an increased volume threshold, contraction amplitude, and residual volume (RV) as well as a decreased burst period (BP) indicated voiding dysfunction in the diabetic rats with sham ES for three or six weeks. However, real ES for three or six weeks reversed these abnormal results; these parameters became similar to those of the NC rats and, consequently, voiding efficiency (VE) increased significantly from 17%–45% to 51%–57%. The cross-sectional area and axonal density of the pudendal nerve decreased in all the diabetic rats with sham ES for six weeks; however, these values increased significantly after real ES for six weeks. Significance. This study demonstrated the feasibility of using chronic pudendal neuromodulation for improving voiding function in diabetic rats. These results may facilitate the development of an advanced neural prosthesis for restoring bladder function in clinical settings.

Urodynamic function during sleep-like brain states in urethane anesthetized rats

The aim was to investigate urodynamic parameters and functional excitability of the periaqueductal gray matter (PAG) during changes in sleep-like brain states in urethane anesthetized rats. Simultaneous recordings of detrusor pressure, external urethral sphincter (EUS) electromyogram (EMG), cortical electroencephalogram (EEG), and single-unit activity in the PAG were made during repeated voiding induced by continuous infusion of saline into the bladder.The EEG cycled between synchronized, high-amplitude slow wave activity (SWA) and desynchronized low-amplitude fast activity similar to slow wave and ‘activated’ sleep-like brain states. During (SWA, 0.5–1.5Hz synchronized oscillation of the EEG waveform) voiding became more irregular than in the ‘activated’ brain state (2–5Hz low-amplitude desynchronized EEG waveform) and detrusor void pressure threshold, void volume threshold and the duration of bursting activity in the external urethral sphincter EMG were raised. The spontaneous firing rate of 23/52 neurons recorded within the caudal PAG and adjacent tegmentum was linked to the EEG state, with the majority of responsive cells (92%) firing more slowly during SWA. Almost a quarter of the cells recorded (12/52) showed phasic changes in firing rate that were linked to the occurrence of voids. Inhibition (n=6), excitation (n=4) or excitation/inhibition (n=2) was seen. The spontaneous firing rate of 83% of the micturition-responsive cells was sensitive to changes in EEG state. In nine of the 12 responsive cells (75%) the responses were reduced during SWA.We propose that during different sleep-like brain states changes in urodynamic properties occur which may be linked to changing excitability of the micturition circuitry in the periaqueductal gray.

Peripheral Nerve Transplantation Combined with Acidic Fibroblast Growth Factor and Chondroitinase Induces Regeneration and Improves Urinary Function in Complete Spinal Cord Transected Adult Mice.

The loss of lower urinary tract (LUT) control is a ubiquitous consequence of a complete spinal cord injury, attributed to a lack of regeneration of supraspinal pathways controlling the bladder. Previous work in our lab has utilized a combinatorial therapy of peripheral nerve autografts (PNG), acidic fibroblast growth factor (aFGF), and chondroitinase ABC (ChABC) to treat a complete T8 spinal cord transection in the adult rat, resulting in supraspinal control of bladder function. In the present study we extended these findings by examining the use of the combinatorial PNG+aFGF+ChABC treatment in a T8 transected mouse model, which more closely models human urinary deficits following spinal cord injury. Cystometry analysis and external urethral sphincter electromyograms reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved bladder and external urethral sphincter histology, and significantly enhanced LUT function, resulting in more efficient voiding. Treated mice’s injured spinal cord also showed a reduction in collagen scaring, and regeneration of serotonergic and tyrosine hydroxylase-positive axons across the lesion and into the distal spinal cord. Regeneration of serotonin axons correlated with LUT recovery. These results suggest that our mouse model of LUT dysfunction recapitulates the results found in the rat model and may be used to further investigate genetic contributions to regeneration failure.

Coital Urinary Incontinence Induced by Impairment of the Dorsal Nerve of the Clitoris in Rats

We determined the effect of chronic bilateral neurectomy of the dorsal nerve of the clitoris on urinary parameters and sexual behavior of conscious female rats. A total of 18 anesthetized virgin female Wistar rats were used in this study, including 11 that underwent bilateral neurectomy of the dorsal nerve of the clitoris and 7 that underwent sham surgery. Urinary parameters were determined in awake animals preoperatively, and 3 and 10days postoperatively. Sexual behavior was tested 14 days postoperatively to determine whether the females expelled urine during sexual encounters. After male ejaculation the females were anesthetized with urethane to record external urethral sphincter electromyogram activity in response to clitoris, perigenital skin and vaginal stimulation. Neurectomy was corroborated anatomically. Sham surgery did not significantly modify urinary parameter values. However, bilateral neurectomy of the dorsal nerve of the clitoris significantly increased voiding frequency and voiding duration (p <0.05). It did not significantly affect the flow rate, voided volume or voiding interval. Of females that underwent bilateral neurectomy of the dorsal nerve of the clitoris 67% expelled urine just after male ejaculation. These results suggest that the pudendal nerve is an important neural pathway in the convergence and crosstalk of female urogenital neural circuits, and genital deafferentation may be a causal factor of coital urinary incontinence. Rats with bilateral transection of the dorsal nerve of the clitoris may serve as an animal model of coital incontinence.

MP1-14 POST-STIMULATION INHIBITION OF BLADDER ACTIVITY INDUCED BY TIBIAL NERVE STIMULATION IN RATS

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 2014MP1-14 POST-STIMULATION INHIBITION OF BLADDER ACTIVITY INDUCED BY TIBIAL NERVE STIMULATION IN RATS Yosuke Matsuta, James Roppolo, William de Groat, Osamu Yokoyama, and Changfeng Tai Yosuke MatsutaYosuke Matsuta More articles by this author , James RoppoloJames Roppolo More articles by this author , William de GroatWilliam de Groat More articles by this author , Osamu YokoyamaOsamu Yokoyama More articles by this author , and Changfeng TaiChangfeng Tai More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.112AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Tibial nerve stimulation (TNS) is useful to treat overactive bladder symptoms. The efficacy of TNS has been reported to be same as antimuscarinics, however, currently the possible mechanisms underlying TNS are not fully understood. The purpose of this study is to develop an animal model for the investigation of the neural mechanisms underlying TNS. METHODS Experiments were conducted in 29 female Sprague-Dawley rats under urethane anesthesia (1.2 g/kg). A catheter was placed into the bladder to perform cystometrogram (CMG). A cuff electrode was placed around right tibial nerve for stimulation. In 24 rats, 3-5 CMGs were performed initially as control CMGs followed by one CMG with simultaneous TNS (5 Hz, 0.2 ms pulse width) at 2 to 4 times the threshold intensity for inducing an observable toe movement. Then, the rats were divided into 2 groups. In the treated group (n=12), TNS was applied for 30 minutes with the bladder empty. In the control group (n=12), the rats were rested for 30 minutes without TNS. Following the 30-minute treatment, 5 CMGs were performed without TNS to evaluate the post-stimulation effect. Bladder capacity (BC), voiding efficacy (VE), maximum voiding pressure (MVP), contraction duration (CD) and bladder compliance were measured. In 5 rats, electromyogram (EMG) was recorded during CMGs to investigate the effect of TNS on external urethral sphincter (EUS) activity. The base-line and the maximal amplitude of EMG activity, bursting duration and frequency during micturition contraction were measured from the EMG recordings. RESULTS TNS applied during CMG had no acute effect on micturition reflex. However, 30-minute-TNS induced significant post-stimulation effects including a 30-40% increase in BC and a 20-30% increase in bladder compliance during the 5 CMGs following the termination of TNS. There was no change in MVP, CD or VE during the following 5 CMGs. TNS did not induce significant changes of EUS EMG activity either during the stimulation or during the post-stimulation period. CONCLUSIONS These results suggest that TNS in rats has no acute effect but has significant post-stimulation inhibitory effect on micturition reflex. TNS has no effect on EUS activity. This animal model will be useful to further investigate the mechanisms underlying the TNS. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e6 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yosuke Matsuta More articles by this author James Roppolo More articles by this author William de Groat More articles by this author Osamu Yokoyama More articles by this author Changfeng Tai More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Effects of agonists for estrogen receptor α and β on ovariectomy-induced lower urinary tract dysfunction in the rat

The postmenopausal hypoestrogen status induces various lower urinary tract dysfunctions. Ovariectomized (OVX) rats exhibit voiding abnormalities, including increased postvoiding residual urine (PVR), decreased voiding efficiency (VE), and altered coordination between the detrusor and external urethral sphincter (EUS). Estradiol replacement partially normalizes voiding function in OVX rats. We determined if selective agonists for estrogen receptor (ER)α and/or ERβ can reverse lower urinary tract dysfunction in OVX rats. Cystometry and EUS electromyograms (EMGs) were recorded 6 wk after bilateral OVX in urethane-anesthetized female Sprague-Dawley rats. Animals received daily subcutaneous injections of selective ERα [propylpyrazole triol (PPT)] or ERβ [diarylpropionitrile (DPN)] agonists or vehicle for 1 wk starting on the fifth week after OVX. PPT (1 mg·kg(-1)·day(-1)) decreased PVR, improved VE, and shortened the EUS EMG active period (AP) during voiding. DPN (2 or 5 mg·kg(-1)·day(-1)) did not alter cystometric parameters or EUS EMG activity. Combined PPT + DPN treatment elicited changes in PVR, VE, and AP, similar to those induced by PPT alone, but also increased the EUS EMG silent period and volume threshold for triggering micturition. PPT increased uterine weight fourfold and decreased body weight by 11%. DPN increased uterine weight 30-45% but decreased body weight by 3-5%. Reduced voiding efficiency in OVX rats can be reversed by 1-wk drug treatment that selectively targets ERα and reduces AP during EUS bursting. Combined pharmacological activation of ERα and ERβ further enhanced EUS bursting by increasing the EUS EMG silent period and also facilitated bladder storage mechanisms by increasing the volume threshold.

2272 PREOPERATIVE DETRUSOR OVERACTIVITY IS A PREDICTOR OF EARLY URINARY INCONTINENCE AFTER ROBOT-ASSISTED LAPAROSCOPIC PROSTATECTOMY

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Urodynamics Testing1 Apr 20132272 PREOPERATIVE DETRUSOR OVERACTIVITY IS A PREDICTOR OF EARLY URINARY INCONTINENCE AFTER ROBOT-ASSISTED LAPAROSCOPIC PROSTATECTOMY Akihiro Yanagiuchi, Hideaki Miyake, Kazushi Tanaka, and Masato Fujisawa Akihiro YanagiuchiAkihiro Yanagiuchi Kobe, Japan More articles by this author , Hideaki MiyakeHideaki Miyake Kobe, Japan More articles by this author , Kazushi TanakaKazushi Tanaka Kobe, Japan More articles by this author , and Masato FujisawaMasato Fujisawa Kobe, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2201AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To investigate changes in the bladder and urethral function and to detect preoperative parameters have an impact on early urinary incontinence after robot-assisted laparoscopic prostatectomy (RALP). METHODS This study included 60 consecutive patients who underwent RALP for clinically localized prostate cancer. Urodynamic study (UDS), including filling cystometry, pressure flow study, electromyogram of external urethral sphincter and urethral pressure profile, were performed in the patients before and 3 months after RALP. In this series, continence was defined as free for pad against urinary incontinence. International prostate symptom score (I-PSS), QOL index, and OABSS were also examined before and at 1 and 3 months after RALP. RESULTS All Patients included in this series could void spontaneously before RALP. On UDS, maximum cystometric capacity (MCC) and bladder compliance after RALP were significantly reduced than those before RALP. The degree of obstructive symptoms was markedly improved postoperatively, resulting in the significant decrease in maximum detrusor pressure 3 months after surgery; however, detrusor contractility was significantly deteriorated postoperatively. Furthermore, maximum urethral closure pressure (MUCP) and functional length (FL) after RALP were significantly decreased compared with those before RALP. In patients with postoperative incontinence, preoperative MUCP and FL were significantly lower than those in patients without incontinence. On multivariable analysis, detrusor overactivity was preoperative independent predictor of stress incontinence at 1M after RALP. CONCLUSIONS These findings suggest that both bladder contraction and external urethral sphincter function were not sufficiently recovered 3 months after RALP, and preoperative detrusor overactivity is a predictor of early stress incontinence after RALP. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e931-e932 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akihiro Yanagiuchi Kobe, Japan More articles by this author Hideaki Miyake Kobe, Japan More articles by this author Kazushi Tanaka Kobe, Japan More articles by this author Masato Fujisawa Kobe, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats

Effects of urethane on lower urinary tract function were examined in decerebrate unanesthetized rats. During single slow infusion (0.04 ml/min) cystometrograms (CMGs), urethane (0.3 g/kg) increased micturition pressure threshold (PT) by 73%, postvoid residual volume (RV) by 425%, and decreased voiding efficiency (VE) by 57%, but did not change maximal voiding pressure (MVP), closing peak pressure (CPP), bladder compliance, bladder contraction duration (BCD), or volume threshold (VT) for inducing micturition. Lower doses (0.01-0.1 g/kg) did not alter any parameter. During continuous fast infusion (0.21 ml/min) CMGs, urethane at doses of 0.6-1.2 g/kg (iv) markedly decreased CPP by 69-85%, whereas only the largest dose (1.2 g/kg iv) decreased MVP and external urethral sphincter electromyogram activity by 42 and by 80%, respectively. Doses of 0.001-0.6 g/kg did not alter the intercontraction interval and BCD. Taken together, these results suggest that urethral activity, which is essential for efficient voiding, is more sensitive to the suppressive effect of urethane than afferent or efferent mechanisms controlling the bladder. The threshold dose of MK-801 (0.3 mg/kg), an NMDA antagonist, required to decrease MVP and increase VT in urethane (1.2 g/kg)-anesthetized rats, only increased VT in rats treated with a subanesthetic dose of urethane (0.3 g/kg), suggesting a higher sensitivity of the afferent vs. efferent limb of the micturition reflex pathway to urethane-MK-801 interactions. Because effects of urethane persisted after removal of the forebrain, they must be mediated by actions on the brain stem, spinal cord, or peripheral nervous system.

Bladder dysfunction changes from underactive to overactive after experimental traumatic brain injury

Although bladder dysfunction is common after traumatic brain injury (TBI), few studies have investigated resultant bladder changes and the detailed relationship between TBI and bladder dysfunction. The goal of this study was to characterize the effects of TBI on bladder function in an animal model. Fluid-percussion injury was used to create an animal model with moderate TBI. Female Sprague–Dawley rats underwent TBI, sham TBI or were not manipulated (naïve). All rats underwent filling cystometry while bladder pressure and external urethral sphincter electromyograms were simultaneously recorded 1day, 1week, 2weeks, and 1month after injury. One day after injury, 70% of the animals in the TBI group and 29% of the animals in the sham TBI group showed no bursting activity during urination. Compared to naïve rats, bladder function was mainly altered 1day and 1week after sham TBI, suggesting the craniotomy procedure affected bladder function mostly in a temporary manner. Compared to either naïve or sham TBI, bladder weight was significantly increased 1month after TBI and collagen in the bladder wall was increased. Bladder function in the TBI group went from atonic 1day post-TBI to overactive 1month post-TBI, suggesting that TBI significantly affected bladder function.