Detrusor Contraction Research Articles

Urodynamic efficacy of fesoterodine for the treatment of neurogenic detrusor overactivity and/or low compliance bladder.

ObjectiveTo examine the urodynamic effects of fesoterodine on neurogenic detrusor overactivity and/or low compliance bladder.MethodsA total of 77 patients (52 men, 25 women; aged 61.6 ± 20.3 years) were given fesoterodine 4–8 mg/day and prospectively followed for 12 weeks. The primary end‐point variable was change in the maximum cystometric capacity on urodynamic study. The secondary end‐point was to assess the number of patients whose neurogenic detrusor overactivity disappeared, and the changes in the urodynamic parameters, lower urinary tract symptoms questionnaires and the 3‐day frequency volume chart parameters after the treatment.ResultsA total of 13 patients (16.9%) withdrew because of adverse events (dry mouth or blurred vision), and four patients dropped out for unknown reasons. Finally, 60 patients completed the study. Bladder capacity at first desire to void, maximum cystometric capacity and bladder compliance increased by 29.2 mL, 79.9 mL and 22.2 mL/cm H2O, respectively, showed statistical significance (P = 0.026, P < 0.001 and P < 0.001). Neurogenic detrusor overactivity disappeared in 12 of 51 patients (23.5%), and a significant increase was observed in bladder capacity at first involuntary contraction (P < 0.001), and a significant decrease was observed in maximum detrusor contraction (P < 0.001). In patients with low compliance bladder (with detrusor underactivity without neurogenic detrusor overactivity; n = 9), maximum cystometric capacity and bladder compliance increased significantly (P = 0.003 and P = 0.006, respectively). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire–Short Form, most items of King’s Health Questionnaire, and the number of urgency episodes and leaks in a day decreased significantly after treatment.ConclusionsFesoterodine seems to be a valid treatment option for neurogenic detrusor overactivity and/or low compliance bladder in neurogenic bladder patients.

Voiding dynamics in women with urinary incontinence but without voiding symptoms.

To describe the voiding pattern (VP) of women with urinary incontinence but without voiding symptoms and compare their clinical and urodynamic features between those voiding with and without a measurable detrusor contraction (DET-cont). Retrospective analysis of a prospectively built database of female urodynamic studies (UDS). Women with voiding symptoms and having medical history of different factors that could alter the lower urinary tract function were excluded. All UDS were performed following the ICS guidelines. DET-cont and abdominal straining (ABD-strain) were defined as an increase ≥10 cm H2 O over the baseline for pdet and pabd at Qmax , respectively. A total of 186 women were included in the analysis. Mean age was 58 ± 10.7 years (24-83). Most women showed a VP with DET-cont (77.4%), with or without ABD-strain. When compared to women voiding without DET-cont, those with DET-cont were younger (P = .004), more likely to have detrusor overactivity (P = .035) and better urinary sphincter competency in the UDS (P = .018). On multivariate analysis, the presence of DET-cont was associated with age ≤50 years (P = .004) and the absence of urodynamic stress urinary incontinence (SUI) or SUI with abdominal leak point pressure ≥100 cm H2 O (P = .008). Most women without voiding symptoms show a VP characterized by a measurable detrusor contraction, with or without ABD-strain. The results suggest that the VP may vary independently with aging and with changes in the state of the urinary sphincter, emphasizing that for the interpretation of micturition in women different aspects must be considered.

Long-term urological assessment and management of cloaca patients: A single tertiary institution experience

PurposePreserving renal function and achieving urinary continence are the most important urological goals in the management of cloaca patients. Many prognostic factors have been described, such as the length of the common channel (CC) and urethra, the presence of spinal dysraphism, and associated urological anomalies. The aim of this study was to analyze urinary continence status and need for reconstructive procedures and their correlation with urological risk factors in a series with a long-term follow-up. Material and methodsThe institutional database of patients with anorectal malformations was reviewed. Patients with cloaca who underwent cloacal reconstructive surgery at our institution between January 1995 and May 2015 and who had a minimum postoperative follow-up of 5 years with complete urological care were included.Urologic and spinal anomalies, length of the CC, renal function, urodynamic study patterns, continence status, and urologic reconstructive surgeries were assessed. A CC was defined as long CC when its measure was longer than 3 cm in the cloacogram and then confirmed by cystoscopy. Descriptive statistical analysis was performed. ResultsFifty-five cloaca patients with a mean follow-up of 12 years (5–20) were included. A long CC was documented in 38 patients (69%). The sacral ratio (SR) was <0.4 in the AP projection in 30 (54.5%). Urodynamic evaluation revealed an inadequate detrusor contraction pattern in 65.4% of the cases. A CC >3 cm and SR <0.4 were significantly correlated with this urodynamic finding. A total of 50 patients (91%) achieved urinary continence, but only 30.9% had volitional voiding and 56% needed major urological reconstructive surgeries. Eighteen patients (32.7%) were in stage 2 or more of chronic kidney disease (<90 ml/min/1.73 m2) at the last follow-up visit. ConclusionCloacal management requires a multidisciplinary and long-term follow-up. Early assessment of prognostic urological factors and accurate stratification of each patient are essential to avoid renal impairment and achieve urinary continence in the future. The length of the common channel and the presence of spinal dysraphism were correlated with the presence of neurovesical dysfunction specifically an abnormal bladder contraction efficiency. A significant number of these patients will need catheterization and reconstructive urinary tract surgeries to attain urinary continence. Type of studyRetrospective study. Level of evidenceLevel 3. Retrospective comparative study.

Artifacts and abnormal findings may limit the use of asymptomatic volunteers as controls for studies of multichannel urodynamics.

Multichannel urodynamics is the gold standard for the evaluation of lower urinary tract symptoms (LUTS). When performing studies to validate new adjuncts to urodynamic testing with control patients undergoing urodynamic investigation, there is difficulty in the interpretation of urodynamic results in the asymptomatic patient due to artifacts and the invasive nature of the procedure. The purpose of this investigation was to examine urodynamics in asymptomatic volunteers in order to better understand the role of control participants in urodynamic research studies. Asymptomatic volunteers with no LUTS were recruited to undergo standard urodynamic testing as a comparison group in a study evaluating novel urodynamic techniques. To be eligible, participants had to report no LUTS, score ≤1 on all symptom questions of the International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIq-OAB) survey, have no medical conditions or to undergo any medications that affect bladder function. The urodynamics was done according to ICS standards. All tracings were evaluated by an expert neuro-urologist. Data were analyzed categorically for the presence or absence of low compliance (<30 mL/cmH<inf>2</inf>0), detrusor overactivity, bladder outlet obstruction (Bladder Outlet Obstruction Index [BOOI]>40), weak contractility (bladder contractility index [BCI]<100), straining to void, poorly sustained detrusor contraction, uncoordinated EMG activity, and intermittent flow. A total of 24 participants completed the study including 10 men and 14 women. All participants had at least 1 urodynamic abnormality/artifact with an average of 4.43±1.28 abnormalities/participant. The most common abnormalities included uncoordinated electromyography (EMG) activity (87.50%), straining to void (79.17%), and intermittent flow (70.83%). There were no significant differences for sex, age, Body Mass Index. This study demonstrated that healthy, asymptomatic volunteers have high rates of abnormal urodynamic findings, suggesting that asymptomatic participants are not the ideal controls in research studies that involve urodynamic testing.

129 - Inhibition of cholinergic, neurogenic, and non-cholinergic/non-neurogenic detrusor contractions by the Rac inhibitor EHT1864

129 - Inhibition of cholinergic, neurogenic, and non-cholinergic/non-neurogenic detrusor contractions by the Rac inhibitor EHT1864

Dysfunctional bladder neurophysiology in urofacial syndrome Hpse2 mutant mice.

Urofacial syndrome (UFS) is an autosomal recessive disease characterized by detrusor contraction against an incompletely dilated outflow tract. This dyssynergia causes dribbling incontinence and incomplete voiding. Around half of individuals with UFS have biallelic mutations of HPSE2 that encodes heparanase 2, a protein found in pelvic ganglia and bladder nerves. Homozygous Hpse2 mutant mice have abnormal patterns of nerves in the bladder body and outflow tract, and also have dysfunctional urinary voiding. We hypothesized that bladder neurophysiology is abnormal Hpse2 mutant mice. Myography was used to study bladder bodies and outflow tracts isolated from juvenile mice. Myogenic function was analyzed after chemical stimulation or blockade of key receptors. Neurogenic function was assessed by electrical field stimulation (EFS). Muscarinic receptor expression was semi-quantified by Western blot analysis. Nitrergic nerve-mediated relaxation of precontracted mutant outflow tracts was significantly decreased vs littermate controls. The contractile ability of mutant outflow tracts was normal as assessed by KCl and the α1-adrenoceptor agonist phenylephrine. EFS of mutant bladder bodies induced significantly weaker contractions than controls. Conversely, the muscarinic agonist carbachol induced significantly stronger contractions of bladder body than controls. The Hpse2 model of UFS features aberrant bladder neuromuscular physiology. Further work is required to determine whether similar aberrations occur in patients with UFS.

Obesity and Overactive Bladder: Is It a Matter of Body Weight, Fat Distribution or Function? A Preliminary Results

ObjectiveTo determine the relationship between subcutaneous fat, visceral fat surface area (VFA), bladder wall fat distribution, and visceral adiposity index (VAI) as risk factors for overactive bladder (OAB) occurrence. Patients and MethodsA cross-sectional study involved 157 participants was conducted. The participants were divided into 2 groups; study group (87 patients diagnosed with OAB) and control group (70 healthy participants). All participants were evaluated for OAB using short-form OABSS version. Physical examination including waist circumference (WC) measurement in addition to metabolic laboratory investigations (eg, High density lipoprotein (HDL), cholesterol, etc) were done. Study group underwent urodynamic testing. Using noncontrast spiral CT abdomen and pelvis, trunkal fat measurements and bladder wall fat distribution were detected. VAI was calculated for both females and males. Univariate and multivariate analyses were done to detect risk factors for OAB occurrence. Correlation between all factors and total OABSS and urodynamics was done. ResultsThe mean age ± SD was 40.4 ± 9 years. In multivariate analysis, increased VFA, higher cholesterol level, increased VAI and focal fat distribution at bladder wall were associated with 9.4, 1.98, 5.5, and 1.6 times higher risk for OAB occurrence. VAI and VFA were strongly correlated with total OABSS, DLPP, amplitude, and frequency of bladder detrusor contractions. On the other hand, WC and body mass index were not correlated significantly. ConclusionBody mass index and WC are crude inaccurate methods correlated with OAB presence. Focal bladder wall fat distribution, higher VAI, higher VFA are novel risk factors for OAB occurrence. Both VAI and VFA are correlated significantly to total OABSS and urodynamics findings in patients with OAB.

The sphingosine-1-phosphate/RhoA/Rho associated kinases/myosin light chain pathway in detrusor of female rats is down-regulated in response to ovariectomy.

BackgroundDysuria is one of the main symptoms of genitourinary syndrome of menopause, which causes serious disruption to the normal life of peri-menopausal women. Studies have shown that it is related to decrease of detrusor contractile function, but the exact mechanism is still poorly understood. Previous results have suggested that the sphingosine-1-phosphate (S1P) pathway can regulate detrusor contraction, and this pathway is affected by estrogen in various tissues. However, how estrogen affects this pathway in the detrusor has not been investigated. In this study, we detected changes of the S1P/RhoA/Rho associated kinases (ROCK)/myosin light chain (MLC) pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.MethodsThirty-six female Sprague-Dawley rats were randomly divided into SHAM (sham operation), OVX (ovariectomy), and E groups (ovariectomy + estrogen), with 12 rats in each group. We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting, respectively. We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay. Finally, we compared results between the groups with one-way analysis of variance.ResultsThe components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased, as compared with SHAM group. The percent decreases of the components in the S1P pathway were as follows: sphingosine kinase 1 (mRNA: 39%, protein: 45%) (both P < 0.05), S1P (21.73 ± 1.09 nmol/g vs. 18.86 ± 0.69 nmol/g) (P < 0.05), and S1P receptor 2/3 (S1PR2/3) (mRNA: 25%, 27%, respectively) (P < 0.05). However, the protein expression levels of S1PR2/3 and the protein and mRNA levels of SphK2 and S1PR1 did not show significant differences between groups (P > 0.05). The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows: ROCK2 (protein: 41%, mRNA: 36%) (both P < 0.05), p-MYPT1 (protein: 54%) (P < 0.05), and p-MLC20 (protein: 47%) (P < 0.05), but there were no significant differences in the mRNA and protein levels of RhoA, ROCK1, MYPT1, and MLC20 (all P > 0.05). In addition, all of the above-mentioned decreases could be reversed after estrogen supplementation (E group vs. SHAM group) (all P > 0.05).ConclusionIn this study, we confirmed that ovariectomy is closely associated with the down-regulation of the S1P/RhoA/ROCK/MLC pathway in the rat detrusor, which may be one mechanism of dysuria caused by decreased contractile function of the female detrusor during peri-menopause.

Continuous Monitoring of Detrusor Pressure in Patients With a Reflex Urinary Bladder After Spinal Cord Injury

In spinal cord injury, the detrusor pressure, as a parameter of urinary bladder dysfunction, is related to incontinence and renal complications. In order to determine the intraindividual variation of maximum pressure and duration of detrusor contractions, in patients with a spinal reflex bladder, the detrusor pressure was registered during 24 hours of physiological filling in 16 patients. Between the bladder contractions the detrusor pressure was low in all patients, indicating high bladder complicance. During contractions the maximum detrusor pressure and its duration varied both inter- and intraindividually. In individual patients, however, mean values during the initial 12 hours correlated with mean values during the final 12 hours. Thus, mean values of a series of contractions appear to be characteristic of each patient and useful in describing the voiding pressure in spinal reflex bladder.

Detrusor pressure in cystometry compared to physiological filling in patients with a reflex urinary bladder after spinal cord injury

The maximum detrusor pressure and the duration of detrusor contractions in 10-50 ml/min fill cystometry were compared to the corresponding measurements during 12 hours of physiological filling, in 18 patients with a reflex urinary bladder after spinal cord injury. In four consecutive cystometries with 10 min intervals the intraindividual variation of the maximum detrusor pressure and the duration of detrusor contractions were similar to the variation during physiological filling. The mean pressure values in cystometries of each patient correlated well with the mean values in registration during physiological filling. In cystometry, there was no significant difference between mean values in 50 ml/min filling compared to 10 ml/min filling nor between mean values in first and second cystometries compared to third and fourth cystometries. Thus, mean values from a series of 10 ml/min or 50 ml/min fill cystometries appear to be as useful as registrations during physiological filling to describe the mean maximum detrusor pressure and the mean duration of contractions in a patient with a spinal reflex bladder.

Ambulatory urodynamic monitoring assessment of dorsal genital nerve stimulation for suppression of involuntary detrusor contractions following spinal cord injury: a pilot study.

A prospective interventional pilot study using within-individual comparisons. To assess the effect of dorsal genital nerve stimulation (DGNS) on urine-storage parameters in participants with spinal cord injury (SCI) and neurogenic detrusor overactivity (NDO) during natural bladder filling. The London Spinal Cord Injuries Centre at the Royal National Orthopaedic Hospital, Stanmore, UK. Ambulatory urodynamic monitoring (AUM) was carried out with and without DGNS, before and after a week of using DGNS at home. DGNS was applied on-demand by four participants with bladder sensation, and both continuously and intermittently by one participant with absent sensation. A Wilcoxon sign-rank test was used to test paired results of changes within an AUM session. Urodynamic outcomes were improved using DGNS. Bladder capacity was increased from 244 ± 59 to 346 ± 61 ml (p = 0.0078), a mean change of 46 ± 25%. Maximum detrusor pressure was decreased from 58 ± 18 to 47 ± 18 cmH2O (p = 0.0156), a change of 17 ± 13%, and average peak detrusor pressure was decreased from 56 ± 16 to 31 ± 128 cmH2O (p = 0.0156), a mean reduction of 50 ± 19%. There was an increase in the number of detrusor contractions from the first involuntary detrusor contraction to a strong desire, urgency or incontinence, from 1.5 ± 1.4 to 4.3 ± 1.7, and an increase in time of 23 ± 22 min. There were no changes in baseline outcomes following home use of DGNS. DGNS may be applied on-demand, intermittently or continuously, to increase bladder capacity, decrease storage pressures and provide extra time. Improvements were made in addition to existing antimuscarinic medication regimes.

Comparison Study of Urinary Retention Incidence in Assisted Vaginal Delivery Case with and without 24-Hour Catheterization

Background: Urinary retention is a condition commonly seen after vaginal delivery, especially in the highrisk cases, such as assisted vaginal delivery, grade 3-4th perineal rupture, or another high risk. Urinary retention caused by unsynchronized between the contraction of the bladder detrusor. Urinary catheterization is one of the preventions of urinary retention. It gives a time for perineal trauma to relieve and no longer edema, so that urethra can be fully relaxed. Therefore, 24-hour catheterization expected to prevent bladder overdistention. It also prevents the bladder from becoming atonia. Objective: This research aims to study the incidence of urinary retention in assisted vaginal delivery with and without 24-hour catheterization. Method: This study used randomized control trials that compared two groups with 24-hour catheterization and without 24-hour catheterization. This study was conducted on 40 women in each group who experienced assisted vaginal birth at Dr Soetomo Hospital, Indonesia. Result: Six women (15%) experienced urinary retention with 24-hour catheterization and six women (15%) had urinary retention without catheterization. There was no significant difference in the incidence of urinary retention with 24-hour catheterization and without 24-hour catheterization (p-value = 1.00). Also, there was no significant interference of urinary retention in the normal and prolonged second stage of labor (p-value = 0.736), and there was no significant risk factor contributing to urinary retention. Conclusion: No significant difference in urinary retention occurred in assisted vaginal delivery with and without 24-hour catheterization

Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766

IntroductionLower urinary tract symptoms (LUTS) due to overactive bladder (OAB) are caused by spontaneous detrusor contractions. Medical treatment with muscarinic receptor antagonists or β3-adrenoceptor agonists aims to inhibit detrusor contractions, but overall results are unsatisfactory. Consequently, improved understanding of bladder smooth muscle contraction and identification of novel compounds for its inhibition are needed to develop alternative options. A role of the GTPase Rac1 for smooth muscle contraction has been reported from the prostate, but is unknown in the human detrusor. Here, we examined effects of the Rac inhibitors NSC23766, which may also antagonize muscarinic receptors, and EHT1864 on contraction of human detrusor tissues.MethodsFemale and male human detrusor tissues were obtained from radical cystectomy. Effects of NSC23766 (100 µM) and EHT1864 (100 µM) on detrusor contractions were studied in an organ bath.ResultsElectric field stimulation induced frequency-dependent contractions of detrusor tissues, which were inhibited by NSC23766 and EHT1864. Carbachol induced concentration-dependent contractions. Concentration response curves for carbachol were shifted to the right by NSC23766, reflected by increased EC50 values, but unchanged Emax values. EHT1864 reduced carbachol-induced contractions, resulting in reduced Emax values for carbachol. The thromboxane analog U46619 induced concentration-dependent contractions, which remained unchanged by NSC23766, but were reduced by EHT1864.ConclusionsNSC23766 and EHT1864 inhibit female and male human detrusor contractions. NSC23766, but not EHT1864 competitively antagonizes muscarinic receptors. In addition to neurogenic and cholinergic contractions, EHT1864 inhibits thromboxane A2-induced detrusor contractions. The latter may be promising, as the origin of spontaneous detrusor contractions in OAB is noncholinergic. In vivo, both compounds may improve OAB-related LUTS.

MP31-09 HOW DO WE DIAGNOSE DETRUSOR UNDERACTIVITY? THE POTENTIAL OF PARAMETERS CALCULATED WITH WATTS FACTOR

INTRODUCTION AND OBJECTIVE: Detrusor underactivity (DU) increases with age. The International Continence Society definition of DU contains two different pathophysiological causes, namely weak detrusor contraction force and abnormally short detrusor contractions. Urodynamic studies have attempted to define DU, but no precise definition is widely accepted. Widely used measurements of bladder contractility are bladder contractility index (BCI) and the Watts factor (WF). Impaired bladder contraction represent not only decreased the peak of WF, but also poorly sustained contractions. From this point of view, the maximum height of the resulting curve (Wmax) and its pattern should be discussed separately. In the present study, we compare several contemporary urodynamic criteria and parameters calculated with WF. METHODS: Thirty five patients with pre and post radical prostatectomy were evaluated. The urodynamic parameters included the maximum flow rate (Qmax), postvoid residual volume (PVR), detrusor pressure at maximum flow (Pdet at Qmax), Wmax, W (Qmax), BCI (bladder contractility index; Pdet Qmax + 5Qmax), rV (Wmax), Line (W), W80-W20 were examined. (Each definition was shown in figure; see figure below) RESULTS: After radical prostatectomy, Qmax increased significantly (pre: 13.6 ± 6.7, post: 18.0 ± 7.0 ml/min; P < 0.01), whereas PdetQmax and PVR decreased significantly (50.6 ± 21.0 and 29.9 ± 16.9 cmH2O, 51.3 ± 61.9 and 15.1 ± 28.6 ml; P < 0.05). BCI, Wmax and W (Qmax) did not change significantly after radical prostatectomy (123.7 ± 36.0 and 114.0 ± 19.9, 11.5 ± 2.8 and 11.1 ± 3.0 W/m2, 8.8 ± 2.6 and 9.7 ± 2.9 W/m2), but rV(Wmax), Line(W), W80 – W20 decreased significantly (0.47 ± 0.3 and 0.20 ± 0.20, −0.0016 ± 0.01 and −0.010 ± 0.01 W/m2/mL, −0.4 ± 2.0 and −2.1 ± 2.6 W/m2; P < 0.05). Wmax and W (Qmax) represents the maximum power of bladder contraction at a particular point in time, whereas rV(Wmax) Line(W), W80 – W20 can be used to detect whole detrusor contraction pattern. The commonly used threshold values for the definition of DU are BCI < 100 or W max < 7 W/m2. In our current study, we couldn’t detect DU using these criteria. However, parameters calculated with WF detect subtle change or pattern of micturition. CONCLUSIONS: The parameters calculated with Watts factor provides some insight into the diagnosis of DU.Source of Funding: none

PD24-10 NICOTINIC RECEPTORS ON NERVE TERMINALS INDUCE ACETYLCHOLINE RELEASE IN CANINE BLADDER

INTRODUCTION AND OBJECTIVE: Carbachol, a mixed muscarinic and nicotinic agonist similar to acetylcholine, is often used for in-vitro bladder contraction with the implicit assumption that it causes contraction by only activating bladder smooth muscle muscarinic receptors. We sought to determine whether nicotinic receptors may also be involved in canine detrusor muscle contractions in- vitro. METHODS: Mucosa denuded canine bladder muscle strips from sham operated animals were used from a larger study of nerve transfer for bladder reinnervation. Strips were fixed between force transducers and positioners and suspended in Tyrode's solution bubbled with 95% O2/5% CO2 at 37 C. After stretching to a length of optimal force production, maximal responses to 120 mM KCl were determined then various agents were added for 20 minutes before inducing contraction with the nicotinic agonists epibatidine and nicotine. RESULTS: Epibatidine induced contractions that were approximately 40% of the maximal response to 120 mM KCl whereas nicotine only induced contractions that were 20% of KCl. The muscarinic receptor antagonist atropine (10 uM) completely blocked 10 uM epibatidine or 1 mM nicotine induced contractions but desensitization of purinergic receptors with 10 uM α,β methylene ATP only blocked these contractions by 40%. Blocking sodium channels with 1 uM tetrodotoxin (TTX) had no statistically significant inhibitory effect on epibatidine or nicotine induced contractions. The α7 nAChR-selective agonist AR-R17779 had no effect and the α7 selective antagonist MLA had no effect at α7 selective concentrations on epidbatidine induced contractions. The α4β2 selective agonist TC2559 also had no effect whereas the α3β4 selective agonist NS3861 and the non-selective ganglionic receptor agonist DMPP induced small contractions. Also, the α3β4 selective antagonist SR-16584 (1-3 uM) blocked eipibatidine induced contractions by 50% . At relatively high concentrations, the skeletal muscle neuromuscular junction nicotinic receptor antagonists atracurium besylate (5 uM) and tubocurarine (0.1 uM) blocked epibatidine induced contractions. At concentrations reported to be selective for ganglionic nicotinic receptors, the neuronal nicotinic receptor antagonists hexamethonium (100 uM) and mecamylamine (10uM) blocked epibatidine induced contractions. CONCLUSIONS: Because of atropine blockade but only minor blockade by α,β methylene ATP desensitization, the nicotinic agonists induce bladder contractions indirectly by releasing predominately acetylcholine from intramural nerve terminals. Because TTX was ineffective, these nicotinic receptors do not need to induce action potentials and thus are likely located near the neuromuscular junction. Based on the pharmacological data, the α3β4 receptor subtype is likely involved in contraction of the canine bladder. Source of Funding: NINDS R01NS070267

Reduced Ca2+ spark activity contributes to detrusor overactivity of rats with partial bladder outlet obstruction.

We tested whether or not altered Ca2+ spark activity accounted for detrusor overactivity (DO) of Wistar rats after partial bladder outlet obstruction (PBOO). We constructed a DO model through PBOO and studied the Ca2+ spark activity of detrusor. By way of using confocal microscopy and the patch-clamp technique, Ca2+ sparks and spontaneous transient outward currents (STOCs) in detrusor myocytes were measured respectively. Our results indicated that Ca2+ spark activity and STOCs were significantly reduced in the DO detrusor myocytes compared to unafflicted control cells, and both of these had levels that were remarkably increased by applications of caffeine (10 μM), a RyR agonist, in DO myocytes. In addition, measures of detrusor contractions were also recorded by using freshly isolated detrusor strips. These results indicated that the spontaneous contraction of DO detrusor was significantly enhanced, and that the effect of caffeine (10 μM) upon detrusor contractions was reversed by applications of iberiotoxin (100 nM) which is a BK channel blocker. Western blotting (WB) analyses indicated that the levels of expression of ryanodine receptor type 2 (RyR2) and FK506 binding protein 12.6 (FKBP12.6) in bladder muscle were respectively decreased and increased in the samples from DO rats. Thus, we considered in the rat DO model wherein PBOO, the reduced Ca2+ spark activity in detrusor myocytes partly contributed to overactive detrusor contractions. The impaired Ca2+ spark activity may have resulted from decreased RyR2 expression and increased FKBP12.6 expression. Such novel findings in our research might help to provide means for better treatment outcomes for patients afflicted by bladder dysfunction.

Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders

Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from purinergic efferent nerves in the detrusor muscle. In afferent nerves, BoNT-A injection markedly reduces the urothelial ATP release and increases nitric oxide (NO) release from the urothelium. BoNT-A injection in the urethra or bladder has been developed in the past few decades as the treatment method for detrusor sphincter dyssyndergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders, including bladder hypersensitivity, overactive bladder, and interstitial cystitis/chronic pelvic pain syndrome. Although the FDA only approved BoNT-A injection treatment for neurogenic detrusor overactivity and for refractory overactive bladder, emerging clinical trials have demonstrated the benefits of BoNT-A treatment in functional urological disorders. Cautious selection of patients and urodynamic evaluation for confirmation of diagnosis are crucial to maximize the successful outcomes of BoNT-A treatment.

Urodynamics mixed type urinary incontinence with advanced pelvic organ prolapse, management and outcomes

Patients with pelvic organ prolapse (POP) often have accompanying lower urinary tract symptoms. Symptoms such as stress urinary incontinence(SUI-UD) and detrusor overactivty(DO) would co-exist in a number of patients. Management entails relieving the obstructive element. To determine the clinical outcome of patients with urodynamics mixed type urinary incontinence(MUI-U) after vaginal pelvic reconstructive surgery(PRS), a retrospective study was conducted. MUI-U was defined as having urodynamic findings of both of DO/DOI (derusor overactivity incontinence) and SUI-UD. Main outcome measures: Objective cure- absence of involuntary detrusor contraction on filling cystometry and no demonstrable leakage of urine during increased abdominal pressure; Subjective cure- assessment index score of <1 on UDI-6 question #2 and #3. Of the 82 patients evaluated, 14 underwent vaginal PRS with concomitant mid-urethral sling(MUS) insertion while 68 had vaginal PRS alone. Pre-operatively, 49(60%) patients had stage III and 33(40%) had stage IV prolapse. Post-operatively, 1-year data shows an objective cure of 56% (46/82) and subjective cure of 54% (44/82). MUI-U was significantly improved. Improvement of SUIUD and results of the 1-hour pad test were more pronounced in patients with concomitant MUS insertion. Ergo, vaginal PRS cures symptoms of MUI-U in >50% of patients and concomitant MUS can be offered to SUI predominant MUI.

Clinical urologic and urodynamic outcomes in patients with anorectal malformation and absent vagina after vaginal replacement

Introduction and objectivesAnorectal malformations (ARMs) represent a complex spectrum of anorectal and genitourinary anomalies and a paucity of evidence is available on long-term urologic outcomes in all ARM subtypes. It was our subjective bias from being a referral center for ARM patients that the subtype of rectovestibular fistula and absent vagina had higher risk of renal and bladder abnormalities than typical rectovestibular fistula patients. Therefore, to confirm or refute our clinical suspicions, the purpose of this study was to review this specific cohort of ARM patients and describe both the clinical urological and urodynamic outcomes. MethodsA retrospective cohort study was performed for 120 patients who were treated for ARM and vaginal replacement at our institution between 1991 and 2017. Fifteen patients with rectovestibular fistula and absent vagina were included in our review. Demographic and clinical data were abstracted from their medical records, including urodynamic findings, need for clean intermittent catheterization (CIC), urinary continence, and renal function. ResultsVaginal replacement surgery was undertaken concomitantly with ARM repair in 10 of the 15 patients (67%). One patient was lost to follow up, and mean follow up postoperatively was 39 months. In all but one patient, rectum or colon was used as the substrate for vaginal replacement. Of the 15 patients, 13 had continence data available. A total of 10 patients (77%) were able to achieve social continence. Overall six patients used CIC to manage their bladder and 40% of continent patients used CIC. Urinary continence outcomes in patients who had partial vaginal replacement compared to those with total vaginal replacement did not reveal a clinically significant difference. Continence was achieved in 3/4 patients (75%) with a history of tethered cord compared to 7/9 patients (78%) without a history of tethered cord release. Urodynamics were performed postoperatively in 7 of the 157 patients (47%). Uninhibited detrusor contractions (UDCs) were present in 3 out of 7 patients, and a cystometric capacity greater than expected was noted in 4 patients. Additionally, 2 patients had end filling detrusor pressure greater than 40 cm H2O. GFR data were available for 13 of the 15 patients and (85%) were classified as chronic kidney disease (CKD) stage I or not having any significant loss of renal function. ConclusionsIn this cohort of rectovestibular fistula and absent vagina, 77% reported achieving urinary continence. However CIC was employed in 40% of the patients which is higher than prior published noncloaca female ARM patient population. Urodynamic abnormalities were noted when performed and led to change in bladder management. Renal function measured with GFR was normal in 85%. Patients with rectovestibular fistula and absent vagina benefit from urologic screening given higher rates of lower urinary tract dysfunction that can require CIC to protect the upper urinary tract and achieve urinary continence. Type of studyCase series. Level of evidenceLevel IV.

Association between bladder fibrosis and oxidative stress in elderly diabetic patients

Objective To investigate the association between bladder fibrosis and oxidative stress in elderly diabetic patients. Methods In this study, 30 elderly patients with bladder fibrosis related diabetes treated in our hospital from June 2017 to December 2017 were selected as the research object (observation group, n=30), and the healthy population (control group 1, n=30) and non bladder fibrotic senile diabetes mellitus (control group 2, n=30) in our hospital during the same period were used as control. Fasting blood glucose, postprandial 2H blood glucose and glycosylated hemoglobin were detected. Bladder dysfunction, urodynamic indexes and oxidative stress indexes were compared between the three groups. Multivariate logistic regression analysis was used to analyze the correlation between serum oxidative stress index and bladder fibrosis in elderly diabetic patients. Results The fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin of control group 2 and observation group were higher than those of control group 1 (P 0.05). The incidence of unstable bladder, low compliance bladder and bladder depression in the observation group was higher than that in the control group 1 and the control group 2 (P<0.05). The maximal urine flow rate and detrusor contraction pressure in the observation group were lower than those in the control group 1 and the control group 2, and the residual urine volume was higher than that in the control group 1 and the control 2 group (P<0.05). The maximum bladder volume, initial urinary bladder capacity and average bladder capacity in the observation group were higher than those in the control group 1 and the control group 2 (P<0.05). The expression level of CAT and SOD in the observation group was lower than that of the control group 1 and the control 2 groups (P<0.05). The expression level of MDA was higher than that of the control group and the control group (P<0.05), and the expression level of CAT and SOD in the control group was lower than that of the control group (P<0.05), and the level of MDA expression was higher than that of the control group 2 (P<0.05). Multivariate logistic regression analysis showed that the expression levels of CAT, SOD and MDA were correlated with the incidence of bladder fibrosis related senile diabetes mellitus (P<0.05). Conclusions Bladder dysfunction in elderly patients with bladder fibrosis has some obstacles, abnormal urodynamic indexes and abnormal expression of oxidative stress indicators. Key words: Diabetes Mellitus; Aged; Urinary Bladder; Fibrosis; Oxidative Stress