Vaginal Distension Research Articles

1592 EFFECT OF NBQX, A NON-COMPETITIVE α-AMINO-3-HYDROXY-5-METHYLISOXAZOLE-4-PROPIONIC ACID RECEPTOR ANTAGONIST, ON THE SNEEZE-INDUCED, ACTIVE URETHRAL CONTINENCE REFLEX IN RATS

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Incontinence - Evaluation & Therapy II1 Apr 20101592 EFFECT OF NBQX, A NON-COMPETITIVE α-AMINO-3-HYDROXY-5-METHYLISOXAZOLE-4-PROPIONIC ACID RECEPTOR ANTAGONIST, ON THE SNEEZE-INDUCED, ACTIVE URETHRAL CONTINENCE REFLEX IN RATS Naoki Kawamorita, Yasuhiro Kaiho, Mabumi Matsushita, Shinichi Yamashita, Hideaki Izumi, Minoru Miyazato, Haruo Nakagawa, and Yoichi Arai Naoki KawamoritaNaoki Kawamorita More articles by this author , Yasuhiro KaihoYasuhiro Kaiho More articles by this author , Mabumi MatsushitaMabumi Matsushita More articles by this author , Shinichi YamashitaShinichi Yamashita More articles by this author , Hideaki IzumiHideaki Izumi More articles by this author , Minoru MiyazatoMinoru Miyazato More articles by this author , Haruo NakagawaHaruo Nakagawa More articles by this author , and Yoichi AraiYoichi Arai More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1370AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urinary continence during stress conditions such as sneezing or coughing is mediated by activation of Onuf′s nucleus in the sacral spinal cord, which induces contractions of striated muscles of the urethral sphincter and pelvic floor. Previous studies have demonstrated that the active urethral closure mechanism during sneezing is enhanced by the activation of noradrenergic and serotonergic systems in rats. However, the effect of glutametergic pathways, which are known to be the major excitatory system controlling the lower urinary tract system, on urethral continence reflex during sneezing has not been clarified. To clarify the role of glutamine pathways on the sneeze-induced urethral closure reflex in rats, we investigated the effects of NBQX, a non-competitive α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor inhibitor, and nisoxetine, a noradrenergic re-uptake inhibitor. METHODS Normal female rats and rats with stress urinary incontinence induced by vaginal distension (VD) were used. Sneezes were induced by a rat′s whisker that was cut and inserted into the nostril. We examined the urethral responses during sneezing caused by active reflex contractions of the mid-urethra. Sneeze-induced leak point pressure (S-LPP) measurements and urethral microtip transducer catheter methods that measured the amplitude of the urethral response during sneezing (A-UPR) and urethral baseline pressure (UBP) were performed. The effects of intrathecal (i.t.) application of NBQX and intravenous (i.v.) injection of nisoxetine (1 mg/kg) on the sneeze-induced continence reflex were examined. RESULTS NBQX dose-dependently inhibited (1, 10, 50, and 100 nmol) A-UPR by approximately 60% without affecting UBP. Nisoxetine increased both A-UPR and UBP; however, following application of NBQX (i.t.) inhibited A-UPR without affecting UBP. In accordance with the change in the microtip transducer catheter method, sneeze-LPPs in VD rats were decreased by NBQX. CONCLUSIONS NBQX (i.t) attenuated the active urethral closure reflex during sneezing. In the presence of NBQX (i.t.), the enhancement of the sneeze-induced reflex after nisoxetine injection at the spinal level was abolished. Taken together, glutamatergic pathways play a crucial role at the spinal level in the active urethral closure mechanism during sneezing. Sendai, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e615-e616 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naoki Kawamorita More articles by this author Yasuhiro Kaiho More articles by this author Mabumi Matsushita More articles by this author Shinichi Yamashita More articles by this author Hideaki Izumi More articles by this author Minoru Miyazato More articles by this author Haruo Nakagawa More articles by this author Yoichi Arai More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1666 ELECTRICAL STIMULATION OF THE PUDENDAL NERVE INCREASES THE EXPRESSION OF NEUROTROPHINS IN ONUF'S NUCLEUS FOLLOWING SIMULATED CHILDBIRTH INJURY

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Female Urology II1 Apr 20101666 ELECTRICAL STIMULATION OF THE PUDENDAL NERVE INCREASES THE EXPRESSION OF NEUROTROPHINS IN ONUF'S NUCLEUS FOLLOWING SIMULATED CHILDBIRTH INJURY Hai-Hong Jiang, Bradley Gill, Levilester Salcedo, Paul Zaszczurynski, Brian Balog, Dan Li Lin, and Margot Damaser Hai-Hong JiangHai-Hong Jiang More articles by this author , Bradley GillBradley Gill More articles by this author , Levilester SalcedoLevilester Salcedo More articles by this author , Paul ZaszczurynskiPaul Zaszczurynski More articles by this author , Brian BalogBrian Balog More articles by this author , Dan Li LinDan Li Lin More articles by this author , and Margot DamaserMargot Damaser More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1490AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A combinatorial injury occurs during childbirth, involving the urethra and pudendal nerve, which can result in stress urinary incontinence (SUI). We have previously demonstrated that dual simulated childbirth injury, consisting of pudendal nerve crush (PNC) and vaginal distension (VD), results in slowed recovery of both continence function & pudendal nerve function, as well as decreased expression of brain derived neurotrophic factor (BDNF). Electrical stimulation has been shown to upregulate BDNF in motor neurons after injury. In this study, we electrically stimulated the pudendal nerve proximal to the crush site to determine if this upregulates BDNF in Onuf's nucleus as a potential treatment to facilitate nerve recovery after childbirth. METHODS Sprague-Dawley female rats were assigned to 3 groups; dual injury (n=5), sham injury (n=5), and intact control (n=5), respectively. Rats in the dual injury group received 4 hours of VD immediately followed by bilateral PNC. Rats in the sham injury group underwent sham procedures. All rats received 1 hour of electrical stimulation (20 Hz, 0.3mA, 0.1 ms duration) of the left pudendal nerve and sham stimulation of the right pudendal nerve immediately after dual or sham injury. The lumbosacral spinal cord was harvested 2 days after stimulation and was flash frozen, sectioned at L6/S1, and laser dissected to isolate Onuf's nucleus (dorsolateral motoneurons in rats). BDNF mRNA expression in Onuf's nucleus was determined by real-time RT-PCR and was normalized to expression of S-18. RESULTS Two days after dual injury, BNDF expression in Onuf's nucleus was significantly decreased in both stimulated and sham stimulated groups compared to that of intact or sham injury. BNDF expression was significantly increased on the stimulated (left) side compared to the sham stimulated (right) side 2 days after dual injury, indicating that electrical stimulation upregulates BDNF expression in Onuf's nucleus. CONCLUSIONS BDNF expression becomes deficient in Onuf's nucleus after a dual childbirth simulation injury. Electrical stimulation of the pudendal nerve proximal to the crush immediately after dual injury upregulated BDNF expression in Onuf's nucleus, suggesting that it will improve recovery after injury. Future work will be aimed at optimizing and developing electrical stimulation to facilitate recovery of the pudendal nerve after childbirth as a preventative paradigm for SUI. Cleveland, OH© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e643-e644 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hai-Hong Jiang More articles by this author Bradley Gill More articles by this author Levilester Salcedo More articles by this author Paul Zaszczurynski More articles by this author Brian Balog More articles by this author Dan Li Lin More articles by this author Margot Damaser More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats

To clarify the role of spinal serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of intrathecal (it) application of 8-OH-DPAT (a 5-HT(1A) agonist), mCPP (a 5-HT(2B/2C) agonist), and fluoxetine (a serotonin reuptake inhibitor) using a rat model that can examine the neurally evoked continence reflex during sneezing. Amplitudes of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, 8-OH-DPAT decreased A-URS by 48.9%, whereas mCPP increased A-URS by 33.6%. However, A-URS was not changed after fluoxetine. 8-OH-DPAT, mCPP, or fluoxetine did not alter UBP. The effect of 8-OH-DPAT and mCPP was antagonized by WAY-100635 (it), a selective 5-HT(1A) antagonist, and RS-102221 (it), a selective 5-HT(2C) antagonist, respectively. Fluoxetine in the presence of WAY-100635 did not change either A-URS or UBP, but fluoxetine in the presence of RS-102221 decreased A-URS. In VD rats, S-LPP was decreased by 14.6 cmH2O after 8-OH-DPAT, whereas it was increased by 12.8 cmH2O after mCPP. However, S-LPP was not changed after fluoxetine. These results indicate that activation of 5-HT(2C) receptors enhances the active urethral closure reflex during sneezing at the spinal level, whereas 5-HT(1A) inhibits it and that no apparent changes in the sneeze-induced continence reflex after fluoxetine treatment are due to coactivation of excitatory 5-HT(2C) receptors and inhibitory 5-HT receptors other than the 5-HT(1A) subtype. Thus, activation of excitatory 5-HT receptor subtypes such as 5-HT(2C) could be effective for the treatment of SUI.

Recovery of Continence Function following Simulated Birth Trauma Involves Repair of Muscle and Nerves in the Urethra in the Female Mouse

BackgroundThe natural history and the mechanisms behind the alteration of vaginal distension (VD) in a mouse model are not clear. ObjectiveWe examined the temporal sequelae of VD and pudendal nerve transection (PNT) on leak-point pressure (LPP) and the muscular and nerve components of the urethra in mice. Design, setting, and participantsSeventy-two virgin female C57BL/6 mice were equally distributed into three groups. The VD group underwent VD for 1h. The PNT group received bilateral PNT. A control group underwent sham VD. InterventionEach group was divided into four subgroups of six mice for measurement of LPP at 0, 4, 10, and 20 d after VD or PNT. MeasurementsLPP was measured. Morphology and neurofilament-immunoreactive nerve of the urethra were assessed. Results and limitationsLPP was decreased at 0, 4, and 10 d but not at 20 d after VD. Decreased LPP persisted to 20 d in the PNT group. The external urethral striated muscle appeared disrupted and/or wavy in two mice at 0 d, in three mice at 4 d, in one mouse at 10 d, and in one mouse in 20 d after VD. The density of neurofilament-immunoreactive nerve in the urethra was reduced at 4 and 10 d after VD, but not at 20 d, and at 4, 10, and 20 d after PNT compared with the corresponding values of the sham VD group. The limitation of this animal model is that the pelvic floor structure of the mouse is different from that of female humans. Therefore, results of this study should be carefully applied to human subjects. ConclusionsVD causes reversible stress urinary incontinence in female mice. Recovery of continence function following VD is associated with repair of the external urethral sphincter and reinnervation of the urethra. This mouse model will be useful for mechanistic investigation and targeting of therapeutic intervention by taking advantage of genetic manipulation.

Dual simulated childbirth injury delays anatomic recovery

A dual childbirth injury model, including vaginal distension (VD) and pudendal nerve crush (PNC), may best represent the injuries seen clinically. The objective of this study was to investigate urethral function, anatomy, and neurotrophin expression after several simulated childbirth injuries. Groups of 140 rats underwent PNC, VD, PNC+VD, or neither (C). Four days after injury, all injury groups had significantly decreased leak-point pressure (LPP) compared with C rats. Ten days after injury, LPP in PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, LPP in all injury groups had recovered to C values. Histological evidence of injury was still evident in the external urethral sphincter (EUS) after VD and PNC+VD 10 days after injury. Three weeks after injury, the EUS of PNC+VD rats remained disrupted. One day after VD, brain-derived neurotrophic factor (BDNF) expression in the EUS was reduced, while neurotrophin-4 (NT-4) and nerve growth factor (NGF) expression was unchanged. BDNF, NT-4, and NGF expression was dramatically upregulated in the EUS after PNC. After PNC+VD, NGF expression was upregulated, and BDNF and NT-4 expression was upregulated somewhat but not to the same extent as after PNC. Ten days after injury, PNC+VD had the least number of normal nerve fascicles near the EUS, followed by PNC and VD. Twenty-one days after injury, all injury groups had fewer normal nerve fascicles, but without significant differences compared with C rats. PNC+VD therefore provides a more severe injury than PNC or VD alone.

Electrophysiological function during voiding after simulated childbirth injuries

During vaginal delivery dual injuries of the pudendal nerve and the external urethral sphincter (EUS), along with other injuries, are correlated with later development of stress urinary incontinence. It is not known how combinations of these injuries affect neuromuscular recovery of the micturition reflex. We investigated the EUS electromyogram (EMG) and the pudendal nerve motor branch potentials (PNMBP) during voiding 4 days, 3 weeks or 6 weeks after injury; including vaginal distension (VD), pudendal nerve crush (PNC), both PNC and VD (PNC + VD), and pudendal nerve transection (PNT); and in controls. Pudendal nerve and urethral specimens were excised and studied histologically. No bursting activity was recorded in the EUS EMG during voiding 4 days after all injuries, as well as 3 weeks after PNC + VD. Bursting activity demonstrated recovery 3 weeks after either VD or PNC and 6 weeks after PNC + VD, but the recovered intraburst frequency remained significantly decreased compared to controls. Bursting results of PNMBP were similar to the EMG, except bursting in PNMBP 4 days after VD and the recovered intraburst frequency was significantly increased compared to controls after PNC and PNC + VD. After PNT, neither the EUS nor the pudendal nerve recovered by 6 weeks after injury. Our findings indicate bursting discharge during voiding recovers more slowly after PNC + VD than after either PNC or VD alone. This was confirmed histologically in the urethra and the pudendal nerve and may explain why pudendal nerve dysfunction has been observed years after vaginal delivery.

Simulated childbirth injuries in an inbred rat strain

Vaginal distension (VD) in outbred rats has been shown to decrease urethral resistance, as well as increase the expression of the stem cell-homing chemokine, monocyte chemotactic factor 3 (MCP-3), but not stromal derived factor 1 (SDF-1). The aim of this study was to determine if similar responses are induced by VD in an inbred rat strain. Forty female Lewis rats underwent VD or sham VD followed by leak point pressure (LPP) testing 4 or 10 days later. Ten additional rats served as controls. The urethra and vagina were then dissected for histology. To examine chemokine expression, eight additional rats underwent VD with organs harvested immediately or 1 day after the procedure for reverse transcriptase polymerase chain reaction (RT-PCR) of MCP-3 and SDF-1. Four age-matched rats served as controls. Four days after VD, LPP was significantly lower in VD rats (14.3 +/- 1.6 cm H(2)O) than controls (18.7 +/- 1.3 cm H(2)O). Ten days after VD, LPP in both VD (19.7 +/- 2.6 cm H(2)O) and sham (18.4 +/- 1.3 cm H(2)O) groups was not significantly different from controls. Urethral histology demonstrated marked disruption and atrophy of smooth and striated muscle in VD rats compared to shams and controls. RT-PCR yielded a 25-fold significant increase in expression of urethral MCP-3 immediately following VD. SDF-1 was significantly decreased in the urethra and vagina immediately after VD and in the bladder 24 hr after VD. VD in Lewis rats produces functional, histological and molecular results similar to that of outbred rats. This model could be utilized in future studies investigating cellular transplant methods of improving urethral function.

Dual Simulated Childbirth Injuries Result in Slowed Recovery of Pudendal Nerve and Urethral Function

Pelvic floor muscle trauma and pudendal nerve injury have been implicated in stress urinary incontinence (SUI) development after childbirth. In this study, we investigated how combinations of these injuries affect recovery. Sixty-seven female Sprague-Dawley rats underwent vaginal distension (VD), pudendal nerve crush (PNC), PNC and VD (PNC + VD), pudendal nerve transection (PNT), or served as unmanipulated controls. Four days, 3 weeks, or 6 weeks after injury, we simultaneously recorded pudendal nerve motor branch potentials (PNMBP), external urethral sphincter electromyography (EUS EMG), and transurethral bladder pressure under urethane anesthesia. The presence of a guarding reflex (increased frequency and amplitude of PNMBP or EUS EMG activity) during leak point pressure (LPP) testing was determined. Controls consistently demonstrated a guarding reflex. Four days after VD, EUS EMG activity was eliminated, but PNMBP activity reflected the guarding reflex; EUS EMG activity recovered after 3 weeks. Four days after PNC, both EUS EMG and PNMBP activity were eliminated, but demonstrated significant recovery at 3 weeks. Four days after PNC + VD both EUS EMG and nerve activity were eliminated, and little recovery was observed after 3 weeks with significant recovery of the guarding reflex 6 weeks after injury. Little recovery was observed at all time points after PNT. LPP results mirrored the reduction in EUS EMG activity. Functional recovery occurs more slowly after PNC + VD than after either PNC or VD alone. Future work will be aimed at testing methods to facilitate neuroregeneration and recovery after this clinically relevant dual injury.

Effect of Prolonged Vaginal Distention and Sphincter Transection on Physiologic Function of the External Anal Sphincter in an Animal Model

Peirce, Colin MB; Healy, Ciaran F. MD; O’Herlihy, Colm MD; O’Connell, P Ronan MD; Jones, James F. X. PhD Author Information

Effect of Prolonged Vaginal Distention and Sphincter Transection on Physiologic Function of the External Anal Sphincter in an Animal Model

Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center Dallas, Dallas, Texas (Wai) ProPath Laboratories, Inc., Dallas, Texas (Miller) Divisions of Urogynecology and Reconstructive Pelvic Surgery and Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center Dallas, Dallas, Texas (Word)

Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse

Matrix metalloprotease (MMP) activity is increased in the postpartum vagina of wild-type (WT) animals. This degradative activity is also accompanied by a burst in elastic fiber synthesis and assembly. The mechanisms that precipitate these changes are unclear. The goals of this study were to determine how vaginal distention (such as in parturition) affects elastic fiber homeostasis in the vaginal wall and the potential significance of these changes in the pathogenesis of pelvic organ prolapse. Vaginal distention with a balloon simulating parturition resulted in increased MMP-2 and MMP-9 activity in the vaginal wall of nonpregnant and pregnant animals. This was accompanied by visible fragmented and disrupted elastic fibers in the vaginal wall. In nonpregnant animals, the abundant amounts of tropoelastin and fibulin-5 in the vagina were not increased further by distention. In contrast, in pregnant animals, the suppressed levels of both proteins were increased 3-fold after vaginal distention. Distention performed in fibulin-5-deficient (Fbln5(-/-)) mice with defective elastic fiber synthesis and assembly induced accelerated pelvic organ prolapse, which never recovered. We conclude that, in pregnant mice, vaginal distention results in increased protease activity in the vaginal wall but also increased synthesis of proteins important for elastic fiber assembly. Distention may thereby contribute to the burst of elastic fiber synthesis in the postpartum vagina. The finding that distention results in accelerated pelvic organ prolapse in Fbln5(-/-) animals, but not in WT, indicates that elastic fiber synthesis is crucial for recovery of the vaginal wall from distention-induced increases in vaginal protease activity.

Cytokine Expression After Vaginal Distention of Different Durations in Virgin Sprague-Dawley Rats

We investigated the effect of the duration of vaginal distention on the differential expression of stem cell homing, tissue repair cytokines and cytokine receptors to identify the factors most important for recovery from injury. A total of 20, 10-week-old virgin Sprague-Dawley rats were divided into 4 groups, including 1, 4 and 6-hour vaginal distention, and anesthetized sham operation. The vagina, bladder, urethra and rectum were harvested immediately after vaginal distention. Real-time polymerase chain reaction was used to determine the relative expression of cytokines and receptors of interest. Mixed models analysis was used to determine associations between expression levels and vaginal distention duration. Positive associations between vaginal distention duration and the urethral expression level were found for 1 of the receptors of monocyte chemotactic protein-3, CCR1 (p = 0.0001) as well as for monocyte chemotactic protein-3 (p = 0.025), CCR5 (p = 0.032) and hypoxia inducible factor-1alpha (p = 0.023). A positive relationship between vaginal distention duration and monocyte chemotactic protein-3 expression was also observed in rectal tissue (p = 0.035). Urethral expression of CCR2, another receptor for monocyte chemotactic protein-3, approached significance (p = 0.066). An inverse relationship between vaginal distention duration and interleukin-8 expression was found in the bladder (p = 0.0008). No association was noted between vaginal distention duration and the expression of stromal derived factor-1, CXCR4, CCR3 and vascular endothelial growth factor in any pelvic organs. These data support a relationship between vaginal distention duration and the subsequent expression of monocyte chemotactic protein-3 and 1 of its associated receptors, CCR1, in the urethra immediately following vaginal distention. The increase in hypoxia-inducible factor1alpha expression in the urethra with prolonged vaginal distention suggests a limited role of tissue ischemia in the immediate response of pelvic organs to vaginal distention.

Malignant pericardial effusion and cardiac tamponade originating from uterine carcinosarcoma

Cardiac tamponade caused by gynecologic malignancies are extremely rare. A 56-year-old woman was referred to our hospital with vaginal bleeding and abdominal distension. Computed tomography showed massive peritoneal fluid, peritoneal dissemination, swelling of the paraaortic lymph nodes and liver metastasis. Endometrial biopsy showed an admixture of both carcinomatous and sarcomatous elements. The final pathological diagnosis was uterine carcinosarcoma, homologous type. After four cycles of chemotherapy consisting of ifosfamide, adriamycin, and cisplatin, we performed laparotomy, and then two additional courses of chemotherapy were administered postoperatively. Eight months after chemotherapy, echocardiography demonstrated massive pericardial effusion with features of tamponade such as diastolic compression of the right ventricle. Cytological examination of the pericardial fluid showed two different cellular patterns, epithelial and non-epithelial components. Although cardiac tamponade is rare and has a poor prognosis, it is important for physicians to consider this possibility in the course of treating of uterine carcinosarcoma.

Recovery of External Anal Sphincter Contractile Function After Prolonged Vaginal Distention or Sphincter Transection in an Animal Model

To estimate the effect of prolonged vaginal distention and anal sphincter transection on contractile properties of the external anal sphincter as a function of time. One hundred thirty-nine young female virginal rats were randomly assigned into four treatment groups (sham, vaginal distention, transection of anal sphincter plus repair, or combined distention and transection plus repair). After 3 days, 3 months, or 6 months, the anal sphincter complex was analyzed for peak force of twitch tension, peak tetanic force, fatigue, and maximal responses to electrical field stimulation. Statistical analysis was performed using analysis of variance (Student-Neuman-Keuls). After 3 days, vaginal balloon distention, anal sphincter transection with repair, and combined distention and transection plus repair resulted in compromise of maximal tetanic contraction and electrical field stimulated force generation. Twitch tension, and resistance to fatigue were also significantly decreased in animals with anal sphincter disruption and repair with and without vaginal distention at 3 days. Contractile function of the external anal sphincter, however, was fully recovered by 3 months and was sustained at 6 months in all treatment groups. The time course of repair was slower in animals with sphincter laceration. Anal sphincter transection with or without antecedent prolonged vaginal distention results in severe compromise of external anal sphincter function in the immediate period after injury. In this animal model, complete recovery of external anal sphincter function occurs 3 months after initial insult.

Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on sneeze-induced urethral continence reflex in rats

We investigated the effect of duloxetine, a norepinephrine (NE) and serotonin (5-HT) reuptake inhibitor, on the neurally evoked urethral continence reflex induced by sneezing in rats. To clarify the role of noradrenergic and serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we examined the effect of duloxetine followed by intrathecal (it) methiothepin maleate (5-HT receptor and alpha1-adrenoceptor antagonist) or terazosin or idazoxan (selective alpha1- and alpha2-adrenoceptor antagonists, respectively). Amplitude of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal adult female rats and rats with SUI induced by vaginal distension (VD). In normal and VD rats, intravenous application of duloxetine (1 mg/kg) increased A-URS by 35% and 34% and UBP by 21% and 34%, respectively. Sneezing-induced fluid leakage from the urethral orifice was observed in VD rats but not in normal rats. S-LPP was increased from 39.1 to 92.2 cmH2O by intravenous duloxetine in incontinent VD rats. Duloxetine-mediated enhancement of A-URS was inhibited by terazosin but not methiothepin maleate (it). In addition, simultaneous intrathecal application of methiothepin and terazosin induced a reduction in A-URS during sneezing, which was not increased by intravenous duloxetine. However, the reduced A-URS after intrathecal application of methiothepin and terazosin returned to the control level when duloxetine (iv) was applied after intrathecal idazoxan administration. These results indicate that duloxetine can prevent SUI by facilitating noradrenergic and serotonergic systems in the spinal cord to enhance the sneeze-induced active urethral closure mechanism.

Effect of Prolonged Vaginal Distention and Sphincter Transection on Physiologic Function of the External Anal Sphincter in an Animal Model

To estimate the effect of prolonged vaginal distention and anal sphincter transection on contractile properties of the external anal sphincter. Young female virgin rats were randomly assigned to four treatment groups (sham, vaginal distention, transection of anal sphincter plus repair, or combined distention and transection plus repair). After 3 weeks, the anal sphincter complex was analyzed for twitch tension, maximal tetanic force, fatigue, and maximal responses to electrical field stimulation. Each sphincter was serially cross-sectioned and stained with hematoxylin and eosin to evaluate sphincter integrity. Statistical evaluation was performed using analysis of variance (Student-Newman-Keuls) and chi2 analysis. The function of a transected and repaired anal sphincter is compromised significantly after 3 weeks. Vaginal distention alone did not alter function of the sphincter. Further, prolonged vaginal distention together with sphincter transection did not result in statistically significant differences in sphincter function compared with transection alone. In an animal model, there is a major effect on external anal sphincter function in vitro 3 weeks after laceration with repair. Although prolonged vaginal distention had no significant effect alone and minimal adverse effects on the lacerated anal sphincter, laceration of the sphincter has major adverse effects on its morphology and function. II.

The electromyographic activity of the external and internal urethral sphincters and urinary bladder on vaginal distension and its role in preventing vaginal soiling with urine during sexual intercourse

We investigated the hypothesis that external (EUS) and internal (IUS) urethral sphincters and urinary bladder (UB) respond to penile thrusting (PT) of vagina in a way that prevents urinary leakage during coitus. Vaginal condom was inflated with air in increments of 50-300 ml and EMG of EUS and IUS and vaginal pressure were recorded; test was repeated after anesthetization of vagina, UB, EUS, and IUS. Vaginal distension effected reduction of vesical pressure but increase of IUS EMG until the 150 ml distension was reached, beyond which more vaginal distension caused no further effect; EUS EMG showed no response. Vaginal distension while vagina, UB, EUS, and IUS had been separately anesthetized, produced no change. Vaginal balloon distension appears to effect vesical relaxation and increased IUS tone. This seems to provide a mechanism to avoid urine leakage during coitus and to occur through a reflex we term 'vagino-urethrovesical reflex'.

Vesicovaginal Reflux Mimicking Obstructive Hydrocolpos

The purpose of this study was to describe a series of cases of hydrocolpos that proved to be due to vesicovaginal reflux. Cases with a diagnosis of hydrocolpos or a fluid-filled vagina identified from our ultrasound database were retrospectively reviewed. The results from sonographic and fluoroscopic studies were reviewed, along with demographic and clinical data. Four patients had sonographic findings mimicking obstructive hydrocolpos that resolved after voiding. Fluoroscopic studies showed abnormal urethral morphologic characteristics in all 4, diminished bladder capacity in 3, and vesicovaginal reflux in 3. No anatomic abnormalities were identified. Vesicovaginal reflux can produce vaginal distension that is sonographically identical to obstructive hydrocolpos. This may be due to dysfunctional voiding issues. Postvoid sonography allows proper diagnosis.

The effect of vaginal distension on the female urinary bladder and urethral sphincters

A mention of effect of vaginal distension, as induced by penile thrusting at coitus, on urinary bladder (UB) and urethral sphincters could not be traced in literature. We investigated the hypothesis that, upon vaginal distension, UB undergoes inhibited activity, while external and internal urethral sphincters (IUS) exhibit increased activity in order to guard against urine leakage during coitus. Response of UB and external and IUS to vaginal balloon distension was recorded in 28 healthy women (age 35.6+/-3.3 years). A vaginal condom was inflated with air in increments of 50 up to 200 ml, and vesical pressure as well as electromyographic (EMG) activity of external and IUS were registered. The test was repeated after separate anaesthetisation of vagina, UB and external and IUS. On vaginal distension, vesical pressure was reduced in the ratio of expansion of vaginal volume up to a certain capacity, beyond which vesical pressure ceased to decline when distending volume was augmented. Similarly, IUS EMG activity increased progressively on incrementally added vaginal distension up to 150-ml distension, beyond which any further vaginal distension did not produce an additional increase of EMG activity; the external urethral sphincter (EUS) EMG activity showed no response. Vaginal distension, while the vagina, UB and external and IUS had been separately anaesthetised, produced no significant change. Vaginal balloon distension seems to effect vesical wall relaxation and increase IUS tone. This appears to provide a mechanism that prevents urine leak during coitus. Vesical and IUS response to vaginal distension are suggested to be mediated through a reflex we term 'vagino-vesicosphincteric reflex', which seems to be evoked by vaginal distension during penile thrusting. The reflex may prove of diagnostic significance in sexual disorders.

A mouse model of simulated birth trauma induced stress urinary incontinence

To facilitate future applications of transgenic or knockout technologies in studies of simulated birth trauma induced stress urinary incontinence (SUI), we aimed to create a mouse model of SUI and explore the possible pathogenesis of this condition. Thirty female C57BL/6 mice were randomly distributed into five groups. Four groups underwent vaginal distention (VD) for 1 hr, using a modified 6-Fr. Foley catheter with a balloon dilated to 0.3, 0.2, or 0.1 ml or sham distention. Four days after VD, all mice underwent leak-point pressure (LPP) measurement via an implanted suprapubic tube (SPT). The normal control group only had SPT placement and LPP measurement. After sacrifice, the urethras of the mice were harvested for routine histological examination and nerve staining. LPPs were significantly lower in groups after VD with 0.3- or 0.2-ml balloon than in control and sham distention groups (10.29 +/- 6.70, 14.65 +/- 6.51, 37.78 +/- 5.10, and 30.30 +/- 5.30 cm H(2)O, respectively). There were no significant differences in LPP between control and sham groups. Histology showed no significant differences in urethral striated muscle among the five groups. The density of immunoreactive neurofilaments in the urethra decreased after VD with 0.3- or 0.2-ml balloon. As a model of birth trauma, VD can induce SUI in female mice, the severity of which is related to intravaginal balloon size. Partial urethral denervation plays a plausible role in the pathogenesis of SUI. This novel mouse model could be used for further mechanistic studies of female SUI.