Improving Bladder Storage Research Articles

Unilateral and Bilateral Transcutaneous Tibial Nerve Stimulation in Women With Overactive Bladder Syndrome: A Randomized Controlled Study (UBTTNS-OAB Study).

The efficacy of unilateral versus bilateral Transcutaneous Tibial Nerve Stimulation (TTNS) for women with Overactive Bladder Syndrome (OAB) remains uncertain. To compare the efficacy of unilateral and bilateral TTNS in the tibial region in women with OAB. This randomized, controlled, triple-blind clinical trial included women with OAB or urgency-predominant urinary incontinence (UUI). Participants were randomized (1:1) into the Unilateral Tibial Group or Bilateral Tibial Group. Before treatment, they underwent a pre-assessment including peripheral sensitivity examination and completion of sociodemographic data and seven validated questionnaires on urinary symptoms, quality of life, sleep, and psycho-emotional aspects. TTNS interventions were administered twice weekly (12 sessions, 30 min each). Posttreatment, participants underwent another physical examination and completed the same questionnaires, with a 30-day follow-up. Categorical variables were analyzed using Chi-square or Fisher's Exact Test, while numerical variables were assessed with the Mann-Whitney test. Group comparisons over time utilized intention-to-treat ANOVA (p < 0.05). Thirty-five women participated: 17 in the unilateral group and 18 in the bilateral group. Mean ages were 55.1 (±14.7) years and 52.7 (±12.6) years, respectively (p = 0.680). Initial OAB severity (ICIQ-OAB) did not differ significantly between groups (p = 0.561). Both groups showed significant improvement in ICIQ-OAB scores: unilateral group from 10.1 (±3.4) to 5.8 (±3.4) (p < 0.001), bilateral group from 9.3 (±3.3) to 5.1 (±4) (p < 0.001), with no intergroup difference (p = 0.395). Improvement in UUI symptoms was observed: unilateral group from 2.2 (±1.4) to 0.7 (±1.5), bilateral group from 1.5 (±1.9) to 0.2 (±0.5), without significant intergroup difference (p = 0.645). Quality of life scores improved similarly between groups (p = 0.055). TTNS appears to be effective in improving bladder storage and UUI symptoms in women with OAB, with no difference between unilateral and bilateral applications. Brazilian Registry of Clinical Trials (REBEC) (RBR: 96f2fgkn).

Nitric oxide‐mediated signal transmission in bladder vasculature underlies the therapeutic actions of PDE5 inhibitors in the rat

Background and PurposeWhile the bladder vasculature is considered as a target of PDE5 inhibitors to improve bladder storage dysfunctions, its characteristics are largely unknown. Thus, the functional and morphological properties of arteries/arterioles of the bladder focusing on the NO‐mediated signal transmission were explored.Experimental ApproachDiameter changes in rat bladder arteries/arterioles were measured using a video‐tracking system. Intercellular Ca2+ dynamics in pericytes or smooth muscle cells (SMCs) of suburothelial arterioles were visualised using transgenic mice expressing GCaMP6 under control of the NG2‐ or parvalbumin‐promoter. The perivascular innervation was investigated using fluorescence immunohistochemistry.Key ResultsIn rat suburothelial arterioles and vesical arteries, tadalafil (100 nM) attenuated nerve‐evoked sympathetic vasoconstrictions. In both vascular segments, tadalafil‐induced inhibition of sympathetic vasoconstriction was prevented by N ω‐propyl‐l‐arginine hydrochloride (l‐NPA, 1 μM), an nNOS inhibitor or N ω‐nitro‐l‐arginine (l‐NA, 100 μM). Both vascular segments were densely innervated with nNOS‐positive nitrergic nerves in close apposition to tyrosine hydroxylase‐immunoreactive sympathetic nerves. In pericyte‐covered pre‐capillary arterioles of the mouse bladder where sympathetic nerves were absent, nerve stimulation evoked transient reductions in pericyte Ca2+ levels that were shortened by l‐NPA and abolished by l‐NA. In SMC‐containing arterioles, tadalafil (10 nM) caused a l‐NPA‐sensitive suppression of sympathetic Ca2+ transients. In mice, nitrergic perivascular nerves were distributed in the arterioles and the pre‐capillary arterioles.Conclusion and ImplicationsBoth nitrergic nerve and nerve‐evoked endothelial NO release appear to be involved in vasodilatory signal transmission in bladder vasculature. The NO‐mediated signal transmission is a potential target for PDE5 inhibitor therapy in bladder dysfunctions.

Improvements in Bladder Function Following Activity-Based Recovery Training With Epidural Stimulation After Chronic Spinal Cord Injury.

Spinal cord injury (SCI) results in profound neurologic impairment with widespread deficits in sensorimotor and autonomic systems. Voluntary and autonomic control of bladder function is disrupted resulting in possible detrusor overactivity, low compliance, and uncoordinated bladder and external urethral sphincter contractions impairing storage and/or voiding. Conservative treatments managing neurogenic bladder post-injury, such as oral pharmacotherapy and catheterization, are important components of urological surveillance and clinical care. However, as urinary complications continue to impact long-term morbidity in this population, additional therapeutic and rehabilitative approaches are needed that aim to improve function by targeting the recovery of underlying impairments. Several human and animal studies, including our previously published reports, have documented gains in bladder function due to activity-based recovery strategies, such as locomotor training. Furthermore, epidural stimulation of the spinal cord (scES) combined with intense activity-based recovery training has been shown to produce volitional lower extremity movement, standing, as well as improve the regulation of cardiovascular function. In our center, several participants anecdotally reported improvements in bladder function as a result of training with epidural stimulation configured for motor systems. Thus, in this study, the effects of activity-based recovery training in combination with scES were tested on bladder function, resulting in improvements in overall bladder storage parameters relative to a control cohort (no intervention). However, elevated blood pressure elicited during bladder distention, characteristic of autonomic dysreflexia, was not attenuated with training. We then examined, in a separate, large cross-sectional cohort, the interaction between detrusor pressure and blood pressure at maximum capacity, and found that the functional relationship between urinary bladder distention and blood pressure regulation is disrupted. Regardless of one’s bladder emptying method (indwelling suprapubic catheter vs. intermittent catheterization), autonomic instability can play a critical role in the ability to improve bladder storage, with SCI enhancing the vesico-vascular reflex. These results support the role of intersystem stimulation, integrating scES for both bladder and cardiovascular function to further improve bladder storage.

Роль фезотеродина в лечении синдрома гиперактивного мочевого пузыря

The muscarinic receptors have been used as target in treatment of overactive bladder (OAB) for a long time. These patients have complaints of urgency, increased urinary frequency and nocturia, sometimes with urinary incontinence (involuntary urine leakage which is associated with abrupt and strong desire to void). Fesoterodine is a prodrug that is structurally and functionally associated with tolterodine and it is the novel drug for OAB treatment. As a result of fesoterodine cleavage by non-specific esterase, the active metabolite 5-hydroxymethyl tolterodine (5-HMT) is formed. Like other antimuscarinic drugs, fesoterodine allows to improve bladder storage function (reducing the frequency of urination) and urgency. For assessing an improvement of the quality of life after treatment by fesoterodine the KHQ questionnaire was used.

Inhibitory effects of tibial nerve stimulation on bladder neurophysiology in rats.

Tibial nerve stimulation (TNS) is a form of peripheral neuromodulation which has been found effective in treating overactive bladder symptoms, with lesser side effects than first line pharmacotherapy. Despite its widespread clinical use, the underlying mechanism of action is not fully understood. Our aim was to study its effect on the bladder neurophysiology and the trigger mechanism of voiding in the overactive detrusor, simulated by acetic acid (AA) instillation. In urethane anaesthetized male Wistar rats, the tibial nerve was stimulated for 30 min at 5 Hz, pulse width 200 µs and amplitude approximately three times the threshold to induce a slight toe movement. The pressure at which a voiding contraction was triggered (pthres) did not change significantly between the pre- and post-TNS measurements in AA induced detrusor overactivity. It was found that TNS significantly reversed the effects of AA irritation by increasing the bladder compliance and the bladder volume at pthres, as well as suppressed the threshold afferent nerve activity. The slope of the linear relationship between pressure and the afferent activity increased after AA instillation and decreased significantly after stimulation. In addition to its well-known central inhibitory mechanisms, this study has demonstrated that TNS improves bladder storage capacity by delaying the onset of voiding, via an inhibitory effect on the bladder afferent signaling at the peripheral level.

114 INHIBITION OF PERIPHERAL FATTY ACID AMIDE HYDROLASE AMELIORATES BLADDER OVERACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research (II)1 Apr 2013114 INHIBITION OF PERIPHERAL FATTY ACID AMIDE HYDROLASE AMELIORATES BLADDER OVERACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS Giorgio Gandaglia, Fabio Benigni, Roberta Buono, Francesco Mistretta, Alessandro Nini, Fabio Castiglione, Francesco Montorsi, and Petter Hedlund Giorgio GandagliaGiorgio Gandaglia Milan, Italy More articles by this author , Fabio BenigniFabio Benigni Milan, Italy More articles by this author , Roberta BuonoRoberta Buono Milan, Italy More articles by this author , Francesco MistrettaFrancesco Mistretta Milan, Italy More articles by this author , Alessandro NiniAlessandro Nini Milan, Italy More articles by this author , Fabio CastiglioneFabio Castiglione Milan, Italy More articles by this author , Francesco MontorsiFrancesco Montorsi Milan, Italy More articles by this author , and Petter HedlundPetter Hedlund Milan, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1493AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Fatty acid amide hydrolase (FAAH) that degrades endocannabinoids and related fatty acid amides has been located to the urinary bladder mucosa. Peripheral and central nervous FAAH are suggested to regulate distinct functions. Although intravesical FAAH inhibition counteracted bladder overactivity (BO) in female rats, a site of action in the central nervous system could not be excluded. We therefore aimed to study the effect on urodynamics of URB-937, a FAAH inhibitor that does not pass the blood-brain-barrier (BBB), in spontaneously hypertensive rats (SHR) with bladder overactivity (BO). METHODS After ethical approval, 7 SHR and 7 age-matched Wistar Kyoto (WKY) control rats underwent bladder catheter implantation. Three days later, bladder function and effects of intravenous (IV) URB-937 administration (1mg/kg) were assessed during cystometries in awake rats. Values are mean±SEM. For comparisons, paired and unpaired T-test was used. RESULTS SHR exhibited BO with increased frequency and decreased bladder capacity and compliance compared to WKY (p<0.01-0.05). In SHR, whereas basal pressure (BP), threshold pressure (TP) and maximum pressure (MP) were unaffected by IV URB-937, flow pressure (FP) decreased from 22.8±1.9 to 20.6±1.8 cmH2O (p<0.05). Moreover, micturition interval (MI), volume (MV) and bladder capacity (BC) increased 19.8%±7.8% from 2.48±0.38 to 2.89±0.4 min, 67.5%±21.8% from 0.29±0.06 to 0.45±0.06 ml and 21.2%±8% from 0.41±0.06 to 0.48±0.06 ml, respectively (all p<0.05), and residual volume (RV) decreased from 0.11±0.04 to 0.03±0.01 ml (p=0.07). In addition, URB-937 increased compliance at flow from 0.02±0.001 to 0.04±0.001 ml/cmH2O (p<0.05). In WKY, after URB-937 administration, MI increased from 6.7±1 to 7.7±0.9 min (p=0.08), MV increased from 1.08±0.17ml to 1.22±0.15ml (p<0.05), and BC increased from 1.13±0.17ml to 1.29±0.15ml (p=0.07). However, no effects were observed on pressures or compliance. CONCLUSIONS Systemic administration of URB-937 reduces frequency and RV, and improves bladder storage capacity and compliance in SHR with BO. Considering that URB-937 does not pass the BBB, the present results support a peripheral function of FAAH in regulation of micturition, and may suggest elevated activity of the endocannabinoid system in this model of BO versus control rats. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e46 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giorgio Gandaglia Milan, Italy More articles by this author Fabio Benigni Milan, Italy More articles by this author Roberta Buono Milan, Italy More articles by this author Francesco Mistretta Milan, Italy More articles by this author Alessandro Nini Milan, Italy More articles by this author Fabio Castiglione Milan, Italy More articles by this author Francesco Montorsi Milan, Italy More articles by this author Petter Hedlund Milan, Italy More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Efficacy of Silodosin for Relieving Benign Prostatic Obstruction: Prospective Pressure Flow Study

We investigated the effect of the new sympathetic α1A-adrenoceptor antagonist silodosin for relieving benign prostatic obstruction by pressure flow study. In this open, nonblinded, prospective study we administered 8 mg silodosin daily for 4 weeks in 60 patients with lower urinary tract symptoms associated with benign prostatic enlargement. As a primary outcome measure, we assessed changes in bladder function and benign prostatic obstruction using pressure flow study. As secondary outcome measures, changes in subjective symptoms and quality of life were assessed by the International Prostate Symptom Score. Objective changes in urination status were also assessed by free uroflowmetry in terms of maximum flow rate and post-void residual urine volume. A total of 57 patients were enrolled for analysis. In the storage phase of the pressure flow study bladder capacity at first desire to void increased significantly with no significant change in maximum cystometric capacity. Of 24 patients 14 (58.3%) with uninhibited detrusor contractions before administration showed apparent improvement in detrusor overactivity after administration, including 6 in whom uninhibited contractions disappeared. In the voiding phase mean detrusor pressure at maximum flow significantly decreased from 72.5 to 51.4 cm H(2)O. The mean bladder outlet obstruction index decreased significantly from 60.6 to 33.8. Obstruction grade assessed by the Schaefer nomogram improved in all except 1 patient. Total symptom and quality of life scores, maximum flow rate and post-void residual urine volume on free uroflowmetry significantly improved. Silodosin improved lower urinary tract symptoms by improving bladder storage function and relieving benign prostatic obstruction.

Long‐term administration of prazosin improves bladder storage function: Results from a study in spontaneously hypertensive rats

To investigate the effects of long-term administration of the α(1) -adrenoceptor antagonist prazosin on afferent inputs from the lower urinary tract (LUT). Twenty female spontaneously hypertensive rats (SHR) were randomized to receive a 4-week course of prazosin (0.12 mg/kg per day) or vehicle; 10 female Wistar-Kyoto (WKY) rats were given vehicle. Prazosin or vehicle was administered via an osmotic pump. The effect of prazosin on urodynamic parameters was determined by continuous cystometry in conscious animals. After cystometry, rats were killed and c-fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. The bladder contraction interval was significantly shorter in untreated SHR compared with WKY rats (2.36 ± 0 vs 4.27 ± 0.12 min, respectively; P < 0.05) and cystometric capacity was decreased significantly in SHR compared with WKY rats. L6 spinal cord c-Fos expression was also significantly greater in SHR than WKY rats. The administration of prazosin significantly increased the micturition interval (4.07 ± 0.58 min; P < 0.05) and bladder capacity, but it did not affect micturition pressure. In SHR, the number of c-Fos-positive neurons was significantly lower following the administration of prazosin compared with vehicle. Increased afferent input from the LUT may induce an increase in urinary frequency in SHR. Furthermore, long-term administration of prazosin can exert inhibitory effects on afferent pathways from the LUT during the storage phase. Reductions of afferent input can result in increased bladder capacity and increased micturition interval.

1975 LONG-TERM EFFICACY OF SILODOSIN ON THE LOWER URINARY TRACT FUNCTION IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA: ASSESSMENT ACCORDING TO PROSTATE SIZE BASED ON PRESSURE-FLOW STUDY

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Medical and Hormonal Therapy1 Apr 20111975 LONG-TERM EFFICACY OF SILODOSIN ON THE LOWER URINARY TRACT FUNCTION IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA: ASSESSMENT ACCORDING TO PROSTATE SIZE BASED ON PRESSURE-FLOW STUDY Yoshihisa Matsukawa, Ryohei Hattori, Masashi Kato, Tokunori Yamamoto, and Momokazu Gotoh Yoshihisa MatsukawaYoshihisa Matsukawa Nagoya, Japan More articles by this author , Ryohei HattoriRyohei Hattori Nagoya, Japan More articles by this author , Masashi KatoMasashi Kato Nagoya, Japan More articles by this author , Tokunori YamamotoTokunori Yamamoto Nagoya, Japan More articles by this author , and Momokazu GotohMomokazu Gotoh Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2200AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Long-term efficacy of α1-adrenoceptor (AR) antagonist in patients with large prostate is of debate. We prospectively investigated the long-term effect of silodosin on the lower urinary tract function in patients with benign prostate hyperplasia (BPH) according to prostate size, using pressure-flow study(PFS). METHODS Silodosin of 8 mg/day was administered to patients with BPH. The patients were classified into 2 groups according to prostate size; small prostate group (SP) (prostate volume <35ml) and large prostate group (LP) (>= 35 ml). Changes in parameters from baseline to 4 weeks and 1 year after administration were assessed in international prostate symptom score (IPSS), and voiding and storage function as measured by PFS. RESULTS Available data from 102 of enrolled 110 patients were analyzed. At baseline, no significant difference was observed in IPSS between LP (n=50, mean prostate volume: 54.3ml) and SP (n=52, 30.6ml). PFS revealed no significant difference in bladder capacity at first desire to void (FDV) and maximum cystometric capacity (MCC), while detrusor pressure at maximum flow rate (PdetQmax) and bladder outlet obstruction index (BOOI) were significantly higher in LP. The frequency of detrusor overactivity was also significantly higher in LP. At 4 weeks after treatment, both groups showed significant improvement in IPSS with no significant inter-group difference. At 1 year, IPSS further decreased in SP, but increased in LP. In PFS, both groups showed a significant increase in FDV and MCC at 4 weeks and further improvement at 1 year with no significant inter-group difference. Disappearance of detrusor overactivity at 4 weeks and 1 year was observed in 50.0% and 44.1% of LP, and 45.0% and 50.0% of SP, respectively. PFS during the voiding phase at 4 weeks demonstrated a significant decrease in PdetQmax and BOOI regardless of prostate size with no significant inter-group difference. However, although the improvement in PdetQmax and BOOI at 4 weeks was maintained to 1 year in SP, these parameters changed for the worse in LP. CONCLUSIONS Silodosin quickly improves bladder storage function and relieves bladder outlet obstruction, regardless of prostate size. However, in long-term administration, an improvement of bladder outlet obstruction may be reversed in patients with large prostate, despite preservation of an improvement in storage function. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e790-e791 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoshihisa Matsukawa Nagoya, Japan More articles by this author Ryohei Hattori Nagoya, Japan More articles by this author Masashi Kato Nagoya, Japan More articles by this author Tokunori Yamamoto Nagoya, Japan More articles by this author Momokazu Gotoh Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Alpha1‐Adrenoceptor Antagonists Improve Bladder Storage Function Through Reduction of Afferent Activity in Rats With Bladder Outlet Obstruction

Using a rat BOO model, we determined whether α1-adrenoceptor (AR) antagonists (silodosin, prazosin) improve the bladder storage function by reducing afferent input from the lower urinary tract. Male rats received partial bladder outlet obstruction or sham surgery were used. Four weeks following surgery, their voiding behavior was measured in a metabolic cage. BOO-rats were administered silodosin, prazosin or vehicle for 2 weeks subcutaneously using osmotic pump. At the post-drug condition, voiding behavior was measured again. The L6 spinal cord was removed and immunostained using anti c-Fos antibody. The rats were also performed continuous cystometry with saline without anesthesia or restraint at the pre- and post-drug conditions. Metabolic cage study showed the voiding behavior of BOO-rats was characterized by increase in frequency of urination and decrease in volume voided. Cystometric evaluation also showed the significant increase both in the number of successive voiding contraction and in contraction pressure. The administration of silodosin or prazosin significantly decreased urinary frequency and the number of micturition reflex but affected neither bladder contraction pressure nor residual volume. The number of c-Fos-positive cell significantly increased in BOO-rats, while significantly decreased in those receiving αl-AR antagonists. The present study demonstrates that α1-AR antagonists silodosin and prazosin have an inhibitory effect on afferent input from the lower urinary tract independently of reducing urethral resistance, and thereby reduce the storage dysfunction secondary to BOO. This result suggests that αl-AR, particularly αlA-AR, may play an important role in the activation of the afferent pathway.

Efficacy of Silodosin for Relieving Benign Prostatic Obstruction: Prospective Pressure Flow Study

We investigated the effect of the new sympathetic alpha1A-adrenoceptor antagonist silodosin for relieving benign prostatic obstruction by pressure flow study. In this open, nonblinded, prospective study we administered 8 mg silodosin daily for 4 weeks in 60 patients with lower urinary tract symptoms associated with benign prostatic enlargement. As a primary outcome measure, we assessed changes in bladder function and benign prostatic obstruction using pressure flow study. As secondary outcome measures, changes in subjective symptoms and quality of life were assessed by the International Prostate Symptom Score. Objective changes in urination status were also assessed by free uroflowmetry in terms of maximum flow rate and post-void residual urine volume. A total of 57 patients were enrolled for analysis. In the storage phase of the pressure flow study bladder capacity at first desire to void increased significantly with no significant change in maximum cystometric capacity. Of 24 patients 14 (58.3%) with uninhibited detrusor contractions before administration showed apparent improvement in detrusor overactivity after administration, including 6 in whom uninhibited contractions disappeared. In the voiding phase mean detrusor pressure at maximum flow significantly decreased from 72.5 to 51.4 cm H(2)O. The mean bladder outlet obstruction index decreased significantly from 60.6 to 33.8. Obstruction grade assessed by the Schaefer nomogram improved in all except 1 patient. Total symptom and quality of life scores, maximum flow rate and post-void residual urine volume on free uroflowmetry significantly improved. Silodosin improved lower urinary tract symptoms by improving bladder storage function and relieving benign prostatic obstruction.

Selective α1A-blocker improves bladder storage function in rats via suppression of C-fiber afferent activity

In the present study, we used animal models to investigate whether the selective α(1A)-blocker silodosin exerts inhibitory effects on detrusor overactivity by modulating C-fiber afferent activity. To desensitize C-fiber afferents, 0.3 mg/kg of resiniferatoxin (RTX) was subcutaneously injected into some female Sprague-Dawley rats 2 days before creation of each model. (1) Left middle cerebral artery occlusion was performed to create a cerebral infarction (CI) model (CI rats). The effects of intravenous (i.v.) and intrathecal (i.t.) administrations of silodosin on cystometrography parameters were evaluated in conscious rats. (2) Rhythmic bladder pressure was recorded in rats under urethane anesthesia. Prostaglandin (PG) E(2) (0.4 mg/mL) was continuously administered intraurethrally, and the effects of intra-arterial (i.a.) silodosin on the micturition reflex (MR) were investigated. (1) Silodosin (i.v.) dose-dependently increased bladder capacity (BC) in CI rats without decreasing bladder contraction pressure, but had no effects on BC in RTX-CI rats. Silodosin (i.t.) markedly increased BC in CI rats, but not in RTX-CI rats. (2) After intraurethral administration of PGE(2), the bladder contraction interval (BCI) was markedly reduced in non-RTX rats, but unchanged in RTX rats. Silodosin (i.a.) significantly prolonged BCI in non-RTX rats receiving intraurethral PGE(2). These results suggest that the α(1A)-AR subtype activates C-fiber afferents, and that consequently α(1A)-blockade can improve bladder storage function.

Clinical Efficacy of α 1‐blocker Naftopidil in Patients with Overactive Bladder Associated with Benign Prostatic Hyperplasia

Objectives: We evaluated the clinical efficacy of α1‐blocker naftopidil in patients with overactive bladder associated with benign prostatic hyperplasia (BPH).Methods: A total of 29 patients (range 50–83 years of age, mean 66.7 years) who had severe storage symptoms associated with BPH were studied. The inclusion criteria were (i) a total of seven or more points in storage symptom scores (frequency, urgency and nocturia) of the International Prostate Symptom Score (I‐PSS) and (ii) a quality of life (QOL) index of two or more. Subjective (I‐PSS and QOL index) and objective (uroflowmetry, post‐void residual and filling cystometry) parameters were evaluated before and 3 months after treatment with naftopidil.Results: Total I‐PSS significantly decreased after treatment, with significant improvement of both storage and voiding symptoms scores and QOL index. Improvement of QOL index was most correlated with the reduction of storage symptoms scores. In nine patients who had involuntary detrusor contractions during filling cystometry before treatment, bladder volume at first desire to void significantly increased (from a mean of 174 to 260 mL), and involuntary detrusor contractions disappeared in three patients after treatment.Conclusion: Naftopidil improves not only voiding symptoms, but also storage symptoms associated with BPH, and is effective for improving bladder storage function in patients with detrusor overactivity.

Improvement in Bladder Storage Function by Tamsulosin Depends on Suppression of C-Fiber Urethral Afferent Activity in Rats

Alpha(1)-blockers improve voiding symptoms by decreasing prostatic and urethral smooth muscle tone. However, to our knowledge the mechanism underlying improvements in storage symptoms is not known. Topical application of prostaglandin E(2) to the rat lower urinary tract stimulates the micturition reflex. Using an animal model we investigated whether the alpha(1)-blocker tamsulosin (Astellas Pharma, Tokyo, Japan) acts on C-fiber afferent activity and, if so, the location of this effect. To induce desensitization of C-fiber afferent activity resiniferatoxin (0.3 mg/kg) was subcutaneously injected in female Sprague-Dawley rats 2 days before experiments. Simultaneous recordings of urethral pressure and rhythmic bladder pressure were made with the rats under urethane anesthesia. Prostaglandin E(2) (0.4 mg/ml) was continuously administered intravesically or intraurethrally to rats pretreated with resiniferatoxin (resiniferatoxin rats) or rats without pretreatment (nonresiniferatoxin rats). We investigated the effects on the micturition reflex of intravenous (2.2 x 10(-1) to 2.2 x 10(3) nM/kg) or intrathecal (0.001 to 0.1 nmol) administration of tamsulosin. The bladder contraction interval was markedly decreased after intravesical or intraurethral administration of prostaglandin E(2) in nonresiniferatoxin rats but it was unchanged in resiniferatoxin rats. This effect was antagonized by the EP1 receptor antagonist ONO-8711 (6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]-5Z-hexenoic acid). Intravenous administration of tamsulosin significantly increased the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2) but it had no effect on nonresiniferatoxin rats receiving intravesical prostaglandin E(2). Intrathecal administration of tamsulosin produced a slight and insignificant increase in the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2). These results suggest that prostaglandin E(2) enhances the micturition reflex through C-fiber afferents and tamsulosin had an inhibitory effect on the C-fiber urethral afferent nerves, thereby improving bladder storage function.

Ureterocystoplasty: Videourodynamic Assessment

We evaluated bladder function outcome in children who underwent ureterocystoplasty based on preoperative and postoperative videourodynamic studies. Between 1977 and 2003, 8 patients with a median age of 6 years who had severe bladder dysfunction underwent ureterocystoplasty as a single surgical procedure. Augmentation was performed in 1 refluxing ureter in 7 patients and with a nonrefluxing megaureter in 1. All patients were evaluated urodynamically before and after augmentation using videourodynamic studies. Preoperative bladder capacity was estimated subtracting the volume trapped inside the refluxing ureter from the total amount of contrast fluid infused into the bladder. Controls included 8 patients matched in age (median 7.8 years) and diagnosis who had undergone ileocystoplasty and were studied with the same urodynamic methodology. Median age in patients with ureterocystoplasty and controls at postoperative urodynamic testing was 7.3 and 11.2 years, respectively. Median cystometric bladder capacity for age before and after ureterocystoplasty was 75% (range 10% to 92%) and 94% (range 49% to 100%), respectively. In the ileocystoplasty group cystometric bladder capacity increased significantly after augmentation (median 44% vs 118, p <0.0005). Comparison of postoperative cystometric bladder capacity between the 2 treatment groups showed significantly higher bladder volumes in the ileocystoplasty group (median 217 vs 290 ml, p <0.02). When we analyzed compliance before and after ureterocystoplasty, no statistically significant difference was found (4.09 vs 10.5 ml/cm water). The same parameter in the ileocystoplasty group was statistically significant (1.6 vs 22.5 ml/cm water, p <0.016). Our retrospective study suggests that, although ureterocystoplasty is a useful method for improving bladder storage abnormalities in properly selected patients, enterocystoplasty is associated with a better storage function outcome.

Tamsulosin: Efficacy and Safety in Patients With Neurogenic Lower Urinary Tract Dysfunction Due to Suprasacral Spinal Cord Injury

We evaluated the efficacy and safety of tamsulosin in patients with neurogenic lower urinary tract dysfunction secondary to suprasacral spinal cord lesions in a 4-week randomized controlled trial (RCT) followed by a 1-year, open label, long-term study. A total of 263 patients were randomized to 4-week double-blind therapy with placebo, or 0.4 or 0.8 mg tamsulosin once daily. Of these, 244 patients completed the RCT, 186 continued long-term tamsulosin therapy (0.4 or 0.8 mg once daily) and 134 completed 1-year treatment. The primary efficacy parameter was maximum urethral pressure (MUP). Although the mean decrease in MUP at 4 weeks in the RCT did not reach statistical significance over the placebo, it was more pronounced with 0.4 (-12.2 cm H2O or -10%) and 0.8 mg (-9.6 cm H2O or -9%) tamsulosin than placebo (-6.5 cm H2O or -3%). In the long-term study there was a statistically significant mean decrease in MUP (-18.0 cm H2O, p <0.001 or -15%) from baseline to end point. In the long-term study tamsulosin also decreased maximum urethral closure pressure, improved several cystometry parameters related to bladder storage and emptying, and increased to a statistically significantly degree, from baseline to end point, mean voided volume based on the micturition diary. There was statistically significant improvement for the International Prostate Symptom Score Quality of Life, as well as several questions about symptoms related to urinary leakage, and 1 question on bladder emptying and frequency, bother and severity of symptoms of autonomic dysreflexia. Finally, 71% of patients improved according to investigators (44% slightly and 27% much improved). Both doses were effective and well tolerated. Long-term tamsulosin treatment (0.4 and 0.8 mg once daily) seems to be effective and well tolerated in patients with neurogenic lower urinary tract dysfunction. The results suggest that it improves bladder storage and emptying, and decreases symptoms of autonomic dysreflexia.

The use of α 1-adrenoceptor antagonists in lower urinary tract symptoms: beyond benign prostatic hyperplasia

The first empirical use of α 1-adrenoceptor antagonists in urology occurred about 25 years ago in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH), or LUTS/BPH. Today, many randomized, controlled trials have provided evidence for the efficacy and tolerability of α 1-adrenoceptor antagonists in LUTS/BPH, and they are the most frequently used initial treatment option for this cause of LUTS. For many years, α 1-adrenoceptor antagonists have also been used empirically in other types of lower urinary tract dysfunction (LUTD), such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and neurogenic LUTD (NLUTD). Several investigators have shown that α 1-adrenoceptor antagonists may be useful in patients with CP/CPPS. This was recently confirmed by a 6-week, double-blind, placebo-controlled pilot study evaluating the efficacy and safety of tamsulosin in 58 CP/CPPS patients. Further well-designed and -powered research into the use of α 1-adrenoceptor antagonists in patients with CP/CPPS is currently ongoing. Several small-scale predominantly open-label studies have suggested that α 1-adrenoceptor antagonists may be of benefit in patients with NLUTD. Data from 2 recent large-scale studies with tamsulosin in patients with NLUTD caused by suprasacral spinal cord injury suggest that long-term tamsulosin treatment improves bladder storage and emptying and also reduces symptoms of autonomic dysreflexia. Tamsulosin has also shown promise in ameliorating (early) storage symptoms and urinary retention associated with transurethral microwave thermotherapy, external-beam radiotherapy, and brachytherapy. In BPH patients presenting with the ultimate form of LUTS—acute urinary retention—treatment with tamsulosin before catheter removal results in a higher success rate of catheter-free voiding. Finally, it seems that α 1-adrenoceptor antagonists may reduce the occurrence of urinary retention after (general) surgery. We can therefore conclude that α 1-adrenoceptor antagonists, such as tamsulosin, may be useful for treating men with LUTS beyond BPH.

Pharmacotherapy of Urinary Incontinence

The most effective pharmacotherapy for decreasing the strength of detrusor contractions, improving bladder storage of urine, and improving patient symptoms is the use of anticholinergic/antispasmodic agents.1 From this category, oxybutynin immediate-release (OIR), oxybutynin extended-release (OXL), tolterodine immediate-release (TIR), and tolterodine extended-release (TLA) tablets constitute first-line therapies (Table 1).2 Differences in efficacy, adverse effects, drug interactions, patient tolerability, administration convenience, and drug cost determine drug selection (Table 1).

Non‐invasive antidromic neurostimulation: A simple effective method for improving bladder storage

Patients with intractably diminished bladder storage function are encountered frequently by neurourologists, occasionally requiring reconstructive surgery for appropriate resolution. Although sacral neuromodulation is a recognized effective therapeutic modality, present techniques are technically demanding, invasive, and expensive. This study investigated the effect of non-invasive third sacral nerve (S3) stimulation on bladder activity during filling cystometry. One hundred forty-six patients underwent standard urodynamic filling cystometry that was then immmediately repeated. Patients in the study group (n = 74) received antidromic transcutaneous sacral neurostimulation during the second fill and the control group (n = 72) underwent a second fill without neurostimulation. A statistically significant increase in bladder storage capacity without a corresponding rise in detrusor pressure was observed in the neurostimulated patients. This improvement in functional capacity is an encouraging finding that further supports the use of this non-invasive treatment modality in clinical practice. Neurourol. Urodynam. 20:73–84, 2001. © 2001 Wiley-Liss, Inc.

BLADDER FUNCTION BEFORE AND AFTER SELECTIVE DORSAL RHIZOTOMY IN CHILDREN WITH CEREBRAL PALSY

Purpose Approximately a third of children with cerebral palsy are expected to present with dysfunctional voiding symptoms. Selective dorsal rhizotomy, which is indicated for managing lower extremity spasticity in children with cerebral palsy, also has the potential of affecting bladder function. We evaluate the impact of selective dorsal rhizotomy on bladder function by comparing preoperative and postoperative symptoms, and urodynamic parameters in children undergoing selective dorsal rhizotomy for spasticity. Materials and Methods We reviewed urodynamic studies in 25 boys and 15 girls with a mean age plus or minus standard deviation of 5.43 +/− 2.1 years who underwent selective dorsal rhizotomy for spasticity at our institution between January 1992 and September 1995. Urodynamics were performed preoperatively only in 22 patients, preoperative and postoperatively in 13, and postoperatively only in 5. Preoperative urodynamic studies were done within 2 weeks of surgery and postoperative studies were done at least 6 months after surgery (mean 1.32 +/− 0.65 years). Results Of the 35 patients with preoperative urodynamic studies total bladder capacity, pressure specific volumes and full resting pressure were abnormal for age in 23 (65.7%). In addition, 17 of the 23 children (74%) were completely asymptomatic. In the group that underwent preoperative and postoperative urodynamic studies there was significant improvement in total bladder capacity (p <0.005) and pressure specific volumes (p <0.005) using the paired Student t test. All children had neurological improvement postoperatively, 5 of 7 (71%) who were incontinent preoperatively became continent and none had deterioration on urodynamics. Conclusions At least half of the children with spastic cerebral palsy have clinically silent bladder dysfunction. Selective dorsal rhizotomy improves spasticity and significantly improves bladder storage characteristics. We propose that urodynamic studies be included in the evaluation of children with spastic cerebral palsy who are possible candidates for selective dorsal rhizotomy to treat lower limb spasticity.