Involuntary Bladder Contractions Research Articles

Drugs for overactive bladder.

In overactive bladder, involuntary bladder contractions due to detrusor overactivity result in urinary urgency, frequency, nocturia, and incontinence. The prevalence of the disorder increases with age. Nonpharmacologic treatment, including bladder training, urge suppression, pelvic floor muscle exercises, constipation management, modification of fluid intake, and avoidance of dietary irritants such as alcohol and caffeine, should be tried first.

Гиперактивный мочевой пузырь: уродинамические особенности гиперактивности детрузора в зависимости от причины нарушений мочеиспускания

The aim of the study was to detect features of detrusor overactivity as an urodynamic phenomenon in patients with different etiology of low urinary tract dysfunction. Materials and methods The study included 283 patients (61% females and 39% males) aged 18-82 years (49.2+/-13.5) with neurogenic overactive bladder (n=197), idiopathic overactive bladder (n=41), radiation cystitis (n=8) and chronic pelvic pain (n=37). All patients underwent an urodynamic study (UDS) in Sverdlovsk Regional Clinical Hospital in the period from 2017 to 2020. Results Detrusor overactivity was detected by UDS in 63.4% patients with idiopathic, 94.2% with neurogenic overactive bladder (OAB) and 2.7% in patients with pelvic pain. Maximal amplitude of detrusor pressure during involuntary bladder contraction was significantly higher in neurogenic dysfunction than in idiopathic (25.76+/-26.21 cm 2 and 10.1+/-3.4 cm 2 respectively, =0.003). According to the ROC-analysis, detrusor pressure amplitude has a high predictor value in the diagnosis of a neurogenic origin of overactive bladder (AUC=0.863, p=0.045). The sensitivity of pressure more than 9.5 cm 20 was 88%. Bladder volume at the time of first involuntary contraction was 137+/-120 ml and 218+/-120 ml (=0.07) for neurogenic and idiopathic OAB respectively. Neurogenic detrusor overactivity followed by urgency incontinence more often than idiopathic (59.5% vs 19.2%). Conclusion Neurogenic detrusor overactivity is characterized by larger amplitude and higher rate of urgency incontinence.

Evaluation of bladder shape using transabdominal ultrasound: Feasibility of a novel approach for the detection of involuntary detrusor contractions.

Conventional assessment of overactive bladder syndrome uses invasive pressure-measuring catheters to detect bladder contractions (urodynamics). We hypothesised that bladder shape changes detected and measured using transabdominal ultrasound scan could provide a non-invasive and clinically useful alternative investigation of bladder contractions. This feasibility study evaluated a novel transabdominal ultrasound scan bladder shape test during conventional urodynamics and physiological bladder filling. The aim was to initially evaluate and refine a non-invasive approach for detecting and quantifying bladder shape changes associated with involuntary bladder contractions. To develop measurement techniques and characterise bladder shape changes during bladder filling, healthy female volunteers (n=20) and women with overactive bladder symptoms who had previously undergone urodynamics (n=30) completed symptom questionnaires and bladder diaries. The bladder shape test protocol included consumption of 1 l water before undergoing serial transabdominal ultrasound scan imaging of the bladder during physiological bladder filling and during episodes of urgency. In a further group of women with overactive bladder (n=22), serial transabdominal ultrasound scan images were captured during urodynamics so that shape changes occurring with bladder contractions could be characterised. In both healthy volunteers and women with overactive bladder, the transverse view of the bladder provided the most reliable plane to characterise and measure bladder shape changes. A sphericity index derived from the ratio between maximum inscribed and minimum circumscribed ellipses (πac2(inner)/πac2(outer)) offered a reliable and reproducible measurement system. Of participants undergoing transabdominal ultrasound scan during urodynamics, there were significant measurable differences in sphericity index between patients with bladder contractions (n=12) and patients with acontractile bladders (p < 0.001). Bladder shape changes detected during physiological filling and urodynamics have provided preliminary evidence to support further research into bladder shape test as a non-invasive diagnostic tool to identify involuntary bladder contractions in patients with overactive bladder syndrome.

To compare the efficacy of tamsulosin and tolterodine in double-J stent-related symptoms: A prospective randomized trial

Background: Stent-related symptoms affect nearly 80% of patients with indwelling ureteral stents. Alpha blockers relieve flank pain by blocking alpha-adrenergic receptors and relaxing the smooth muscles of ureter, trigone, and prostatic urethra, thus reducing bladder outlet resistance and voiding pressure, whereas mechanism of anticholinergic drugs involves relief of involuntary bladder contractions that are mediated by muscarinic receptors. We have compared alpha blocker and anticholinergic drugs in reducing stent discomfort. Materials and Methods: The study was conducted from March 2017 to February 2018. A total of 100 patients with unilateral double-J ureteral stenting were randomized, postoperatively into two groups: tamsulosin 0.4mg daily (Group I) and tolterodine 4mg daily (Group II). Results: The mean age was 39.1 years in Group I and 38.0 years in Group II. The male:female ratio in Group I and Group II was 1.38:1 and 1:1, respectively. There was statistically significant difference in urinary symptom score, pain score, and general health score between the two groups in favor of Group I (tamsulosin 0.4mg) at 1week post-stenting and 4 weeks (at stent removal). Conclusion: Oral medication, with uroselective alpha blockers, in patients with indwelling stents reduces stent-related symptoms and negative impact on quality of life.

Efficacy of Peripheral Lidocaine Application (Neural Therapy) in the Treatment of Neurogenic Detrusor Overactivity in Multiple Sclerosis Patients

Aims Many agents and treatments are used in the treatment of neurogenic detrusor overactivity (NDO) in MS patients, but no study has been conducted on the use of peripheric lidocaine (neural therapy-NT) on MS patients. We evaluated the effects of local administration of lidocaine on NDO in Multiple Sclerosis (MS) patients. Methods For each patient local anesthetic lidocaine was injected at each session. Sessions were held once a week for 5 weeks. At each session, Th 10-L1, urogenital segment intradermal injections, Frankenhauser, and sacral epidural injections were given. The patients had clinical and urodynamic assessment 1 month before and 3, 9, and 12 months after NT. In addition, multiple sclerosis quality of life inventory (MSQL-54) and bladder control scale (BLCS) was performed for patients. Results Twenty-eight patients were included in the study (8 males, 20 females). The patients' average age was 31.7 ± 8.1 years. The injection therapy significantly improved volume at first involuntary bladder contraction (FCV), maximal detrusor pression during filling (P det. max.), maximal cystometric bladder capacity (MCC) after 3 months. Also, the MSQL-54 and BLCS scores were improved with treatment. However, these improvements reached a maximum 3 months after treatment, but from the 9 month a regression was seen in the parameters, and after 12 months the findings were seen to be slightly above their basal levels. Conclusions These results suggest that NDO treatment in MS patients could be an effective treatment which is easy and has very few side effects, and is cost effective.

Efficacy of peripheral lidocaine application (neural therapy) in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients.

Many agents and treatments are used in the treatment of neurogenic detrusor overactivity (NDO) in MS patients, but no study has been conducted on the use of peripheric lidocaine (neural therapy-NT) on MS patients. We evaluated the effects of local administration of lidocaine on NDO in Multiple Sclerosis (MS) patients. For each patient local anesthetic lidocaine was injected at each session. Sessions were held once a week for 5 weeks. At each session, Th 10-L1, urogenital segment intradermal injections, Frankenhauser, and sacral epidural injections were given. The patients had clinical and urodynamic assessment 1 month before and 3, 9, and 12 months after NT. In addition, multiple sclerosis quality of life inventory (MSQL-54) and bladder control scale (BLCS) was performed for patients. Twenty-eight patients were included in the study (8 males, 20 females). The patients' average age was 31.7 ± 8.1 years. The injection therapy significantly improved volume at first involuntary bladder contraction (FCV), maximal detrusor pression during filling (P det. max.), maximal cystometric bladder capacity (MCC) after 3 months. Also, the MSQL-54 and BLCS scores were improved with treatment. However, these improvements reached a maximum 3 months after treatment, but from the 9 month a regression was seen in the parameters, and after 12 months the findings were seen to be slightly above their basal levels. These results suggest that NDO treatment in MS patients could be an effective treatment which is easy and has very few side effects, and is cost effective.

Botulinum toxin injections for treating neurogenic detrusor overactivity.

Neurogenic detrusor overactivity (NDO) is a disorder that can cause high intravesical pressure, decreased capacity, decreased bladder compliance, and upper urinary system damage. The current treatment options for NDO are established on the basis of agents that block parasympathetic innervation of the detrusor and inhibit involuntary bladder contractions. Several side effects, such as dryness of mouth, constipation, dyspepsia, changes in visual accommodation, somnolence, and being unable to obtain consistently favorable results, caused by anticholinergic agents, which are frequently used for this purpose, decrease the patient's compliance to treatment. Procedures such as neuromodulation, auto-augmentation, and enterocystoplasty are surgical options, and they could be used as the last alternative. Thus, botulinum toxin (BTX) injections to the detrusor have been commonly performed in recent years and lead to satisfactory results. The mechanism of action of BTX in NDO is based on the principal of smooth muscle relaxation in the bladder by the transient inhibition of neuromuscular nerve signals. The aim is to decrease acetylcholine secretion by blocking presynaptic vesicles in the neuromuscular junction. When studies were evaluated, it was observed that BTX injections to the detrusor muscle are a necessary and effective option in patients with incontinence caused by NDO. This treatment option could be indicated in situations where anticholinergic agents are not effective or could not be tolerated, and it could be a valuable alternative to major surgical treatments. In this review, we evaluated the effectiveness and reliability of BTX in patients with NDO.

Vesico-ureteral reflux in women with idiopathic high-pressure detrusor overactivity: prevalence, bladder function, and effect on the upper urinary tract.

To assess the prevalence of vesico-ureteral reflux (VUR) and upper urinary tract damage in women with idiopathic high-pressure detrusor overactivity (IHPDO) and to characterize their bladder function. A retrospective chart review of women diagnosed with IHPDO (detrusor pressures > 40 cm H2O during involuntary bladder contractions) from 2007 to 2010 was conducted. Women were assessed for VUR by X-ray voiding cysto-urethrogram. Renal ultrasound or CT urogram, serum BUN/creatinine, and urinalyses were performed if reflux reached the renal pelvices. Cystometric and voiding pressure study data were reviewed for detrusor overactivity pressure and volume, voiding dysfunction, urethral relaxation, compliance, and bladder outlet obstruction. Sixty-five women were diagnosed with IHPDO, and 50 completed an X-ray voiding cysto-urethrogram. The median (range) detrusor overactivity pressure was 65 (41-251) cm H2O. Four (8.0%) women had IHPDO; none had upper urinary tract deterioration. The majority of women exhibited urethral relaxation with voiding, impaired compliance, and bladder outlet obstruction. Women with IHPDO are at risk of low-grade vesico-ureteral reflux. However, most women with IHPDO are likely protected from reflux by intermittent exposure to high detrusor pressures and the ability to decompress the bladder by urethral relaxation.

Mirabegron for Male Lower Urinary Tract Symptoms

Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in men. Patients with BPH often present with a combination of obstructive and overactive bladder (OAB) symptoms. It is postulated that bladder outlet obstruction (BOO) from BPH results in concomitant OAB symptoms through ischemic induced variations in the response to neurotransmitters of both the detrusor and the urothelium. This altered response leads to the pathologic activation of the micturition reflex, generating sensory dysfunction and involuntary bladder contractions. Alpha-1 adrenoceptor antagonists (alpha-blockers) and 5-alpha reductase inhibitors (5-ARIs) are commonly used to treat the BOO caused by BPH. Anticholinergic agents are frequently used to treat concurrently OAB symptoms caused by the BOO. Unfortunately, anticholinergic medications demonstrate bothersome side effects and a theoretical risk of urinary retention. Basic science and clinical research has led to the development of a new class of pharmaceuticals for the treatment of overactive bladder with diminished risk of urinary retention and lacking many anticholinergic side effects. This novel compound, mirabegron (Mybertriq, Astellas Pharma US, Inc.), is a β₃-adrenoceptor agonist and represents a promising new class of oral agents designed for the treatment of OAB symptoms, with minimal effect on voiding.

Oxybutynin: past, present, and future

Oxybutynin chloride is primarily indicated for the treatment of overactive bladder syndrome (OAB). It remains the most widely prescribed compound for OAB in the world. OAB is defined as the presence of urinary urgency, usually accompanied by daytime urinary frequency and nocturia, with or without urgency urinary incontinence, in the absence of infection or other identifiable etiology. This is a significant problem for men and women said to affect over 33 million adults in the USA, with the prevalence increasing with age. These symptoms can alter quality of life, with both physical and psychological impairment, as well as cause significant financial burden including the cost of sanitary supplies and decreased work productivity. Both pharmacological and non-pharmacological methods may be employed to aid in the treatment of OAB. The mainstay of treatment for OAB relies on pharmacological management, most specifically treatment with antimuscarinic medications. These medications are thought to prevent involuntary bladder contractions and/or urgency by inhibiting the muscarinic receptors within the urothelium and detrusor muscle. Currently, there are six different medications approved by the US Food and Drug Administration (FDA) for the treatment of OAB, with more than nine formulations including immediate- and extended-release tablets, transdermal patch and gel, vaginal ring, and suppository. This review will focus specifically on oxybutynin chloride, which has been used to treat OAB for four decades in numerous formulations.

Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients

Neurogenic detrusor overactivity (NDO) is common in patients who suffer from multiple sclerosis (MS). When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A) injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor), improvement, or total failure (urge incontinence and overactive detrusor). 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001), maximum cystometric capacity (p = 0.0035), maximum detrusor pressure (p = 0.0000001). 46% of the patients were in the "full success" group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015). Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anti cholinergic drugs fail to reduce NDO.

Botulinum toxin therapy for nonneurogenic overactive bladder: first experience

The paper presents early experience in the treatment of 20 patients with botulinum toxin injections into the detrusor muscle for the treatment of non-neurogenic overactive bladder (OAB) resistant to anticholinergic drugs. Background. Botulinum toxin, a presynaptic neuromuscular blocking agent, reduces the involuntary bladder contractions that cause urgency, frequency and urge incontinence. We present our early experience with Dysport® injections into the detrusor for the treatment of non–neurogenic overactive bladder (OAB) resistant to anticholinergic drugs. Materials and methods. Using intravenous anaesthesia, 20 patients (18 female and 2 male) with non-neurogenic OAB were injected with botulinum toxin A (Dysport®250 IU diluted in 4 ml normal saline) under cystoscopic visualization in 20 sites in the detrusor muscle, sparing the trigone. The urethral catheter was removed 24 hours after the procedure. Follow-up at 3 and 6 months after the injection included the Urogenital Distress Inventory UDI-6, the Incontinence Impact Questionnaire IIQ-7, clinical parameters and ultrasound measurement of bladder capacity and post-void residual urine volume. Results. All 20 patients completed questionnaires and were examined after 3 and 6 months. At the 3-month follow-up, the median daytime micturation frequency decreased from 10.4 to 4.6 times (p &lt; 0.0001) and at the 6 months follow-up 5 times (p &lt; 0.0001), while nocturia decreased from 4.2 to 1.3 times after 3 months (p &lt; 0.0001) and after 6 months to 2 times (p &lt; 0.0001). Urgency decreased from 6 to 1.5 times after 3 months (p &lt; 0.0001) and to 2 times after 6 months (p &lt; 0.0001), and incontinence decreased from 4.2 times to 1.5 times after 3 months (p &lt; 0.0001) and to 2.1 times after 6 months (p &lt; 0.0001). The median maximum bladder capacity increased from 250 to 420 ml after 3 months (p &lt; 0.0001) and decreased to 350 ml after 6 months (p &lt; 0.0001). The post-void median residual urine volume was 10 ml. Only one patient mentioned a post-operative obstructive voiding difficulty. Eighteen (90%) patients were satisfied with the treatment. In two patients (10%), the amelioration of symptoms lasted for one month only, and later OAB symptoms reappeared. Analysis of the UDI-6 and IIQ-7 questionnaires revealed that botulinum toxin A intradetrusor injection had decreased discomfort for patients and ameliorated their quality of life. Conclusions. Botulinum toxin A injections in the detrusor are effective for the treatment of non-neurogenic OAB. Botulinum toxin A injections are a minimally invasive therapy and offer an alternative treatment for non–neurogenic OAB dysfunction resistant to conservative treatment. The durability of the treatment effect is the objective of the further investigation. Keywords: botulinum toxin, overactive bladder, urinary incontinence

Peripheral blood mononuclear cell gene array profiles in female patients with involuntary bladder contractions

Background: Patients with urgency represent a group of incontinence sufferers whose diagnosis remains difficult to establish. Urodynamic testing demonstrating involuntary bladder contraction provides objective confirmation but represents an invasive approach. We have previously demonstrated that peripheral blood mononuclear cells (PBMC) can provide a reporter function in solid organ disease toward biomarker discovery. Here we investigated the utility of using PBMC as marker for patients with confirmed involuntary bladder contraction. Methods: Fifteen female patients were evaluated for involuntary bladder contractions and stress urinary incontinence as demonstrated by urodynamics and also assessed for pelvic prolapse, stress incontinence by history, bladder neck dysfunction, and bladder capacity. PBMC were obtained from patients’ whole blood, and RNA was subjected to microarray gene chip analysis. Results: Microarray analysis revealed that eleven genes were differentially regulated (five upregulated and six downregulated). Of these, PGRMC1 (progesterone receptor membrane component 1), EIF2S3 (eukaryotic initiation factor), C3AR1 (complement receptor), and three unknown genes were downregulated. Upregulated genes included MYOM2 (myomesin M-protein), a cytoskeletal protein; KTN1 (kinectin); and AAK 1 (AP2 associated kinase). Conclusions: Microarray analysis revealed many genes that were differentially regulated in PBMC from patients with involuntary detrusor contractions. These genes may be important in regulating structural integrity of bladder and supporting tissues. These data suggest that PBMC can provide a reporter function for patients with involuntary bladder contractions and may serve toward biomarker discovery for novel diagnostic markers and/or the ability to monitor response to therapy.

The Prevalence and Therapeutic Effect of Constipation in Pediatric Overactive Bladder

PurposeOveractive bladder (OAB) is a manifestation of urgency, regardless of urge incontinence, due to involuntary bladder contraction during the storage period. There is a close association between constipation and OAB, but constipation cannot be readily diagnosed. The aims of this study were to evaluate the prevalence of constipation in OAB and the consequent therapeutic effects according to the diagnostic criteria for constipation.MethodsWe collected clinical data from 40 children (mean age, 71±22 months) with chief complaints of urgency, frequency, and incontinence. A voiding questionnaire and a 2-day voiding diary were collected, and urinalysis, the Bristol stool scale, and plain abdominal radiography were performed. Constipation was defined as conditions satisfying at least one of the following criteria: Rome III diagnostic criteria, Bristol stool scale types I/II, or a Leech score higher than 8 points as determined by plain radiography. Lower urinary tract symptoms, defecation symptoms, and the bladder volume of patients were examined, and the therapeutic outcomes by constipation diagnostic criteria were evaluated.ResultsOf the 40 OAB patients, 25 had constipation. Among them, 6 had reduced functional bladder capacity (24%; P>0.05). Regarding treatment, in patients who satisfied only one diagnostic criterion, the symptoms improved in 76.9%, 76.9%, and 69.6% of patients meeting the Rome III criteria, Bristol stool scale, and Leech score, respectively (P<0.05). Among the 8 patients satisfying all three criteria, 75% responded to treatment (P<0.05).ConclusionsThe prevalence of constipation in OAB is high. Constipated patients recruited by use of the Rome III criteria, Bristol scale, and Leech score alone and together showed similar outcomes on OAB improvement after the treatment of constipation, which implies that each criterion has the same strength and can be applied comprehensively and generally.

Near-Infrared Spectroscopy: A Novel, Noninvasive, Diagnostic Method for Detrusor Overactivity in Patients with Overactive Bladder Symptoms—A Preliminary and Experimental Study

BackgroundNear-infrared spectroscopy (NIRS) is an optical technology. It detects the hemodynamic changes in tissues via noninvasive measurement of changes in the concentration of tissue chromophores such as oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb). Involuntary bladder contractions may cause changes detectable by NIRS. ObjectiveTo address the accuracy and reproducibility of NIRS to detect the hemodynamic effects of detrusor overactivity (DO). Design, setting, and participantsA prospective cohort study was carried out on 41 patients with overactive bladder symptoms. MeasurementsForty-one patients underwent one or more filling cystometries with simultaneous NIRS of the bladder. The separated graphs representing both tests were presented to three urodynamicists on two occasions, 3 wk apart. The graphs showed curves with and without DO episodes with the bladder sensations marked. Thirteen of 47 graphs (28%) with DO and 16 of 58 graphs (28%) without DO were excluded due to motion artifacts. The urodynamicists marked pressure changes suggestive of DO on the cystometry curves. For NIRS curves they marked definite deviations from baseline. The sensitivity and specificity of NIRS for DO were determined. The inter- and intraobserver agreements were determined. Results and limitationsValid data from 33 of 41 patients (80%) were included in the analysis. The interobserver agreement to trace the effect of DO on NIRS curves was “substantial” (κf>0.6). The sensitivity of the Hbsum (O2Hb+HHb) curves for DO was 62–97% with a specificity of 62–79% (area under the curve [AUC]: 0.80–0.82; p<0.001). O2Hb curves had 79–85% sensitivity and 82–91% specificity for DO (AUC: 0.80–0.85; p<0.001). The sensitivity and specificity of the HHb curves for DO were 71–82% and 77–82%, respectively (AUC: 0.73–0.84; p<0.001). These values represent the performance of NIRS in the data sample that is not contaminated with motion artifacts; they are not representative of a general clinical setting. ConclusionNIRS is a potential noninvasive, reproducible, diagnostic method to detect DO.

In vitro effects of the cyclooxygenase inhibitor indomethacin and of the phospholipase‐C inhibitor U‐73122 on carbachol‐induced contractions of porcine detrusor muscle

Prostaglandin synthetase inhibitors belong to one substance class additionally used in the treatment of bladder dysfunctions associated with involuntary bladder contractions. However, the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) on the detrusor muscle is not clear. In this study, it was examined in vitro whether the NSAID indomethacin exhibited an inhibitory effect on carbachol-induced contractions of the porcine detrusor muscle. Additionally, the inhibitory effect of the phospholipase-C inhibitor U-73122 on carbachol-induced contractions of the porcine detrusor muscle was investigated. Experiments were performed on the muscle strips of the porcine detrusor muscle suspended in a tissue bath. Effects of indomethacin at 10(-6) and 10(-5) M on the maximum carbachol-induced contraction and on the carbachol-response curve were investigated. Additionally, the inhibitory influence of U-73122 at a concentration of 10(-5.5) M on the carbachol-response curve was investigated. Pretreatment with indomethacin at both concentrations did not result in a significant reduction in the maximum contraction compared with the control. In the experiments in which carbachol concentration-response curves were generated, indomethacin exhibited at both concentrations a very small but significant change at carbachol concentrations of 10(-8) and 10(-7.5) M. In the experiments with U-73122, a significant change was found in the concentration-response curve of carbachol at all concentrations of carbachol from 10(-6.5) to 10(-4) M. The mean maximum carbachol-induced contraction was 141.8 +/- 6.8% after incubation with U-73122 and 166.0 +/- 6.4% in the control group (P < 0.05). Indomethacin did not inhibit the carbachol-induced contractions of the porcine detrusor muscle. The cyclooxygenase does not play a significant role in the carbachol-induced bladder contraction of the porcine detrusor muscle. The inhibitory action of the phospholipase-C inhibitor U-73122 on the carbachol-induced contraction was significant, but small. The results point to an inferior role of this pathway.

Pharmacotherapy for Nocturia in the Elderly Patient

Nocturia may be attributable to nocturnal polyuria (nocturnal urine overproduction), a diminished nocturnal bladder capacity or a combination of the two conditions.A disorder of the vasopressin (antidiuretic hormone) system with very low or undetectable levels of vasopressin at night, affecting some elderly people, may cause an increase in the nocturnal urine output, which in the most extreme cases accounts for 85% of the 24-hour diuresis. The increased urine output can be treated with desmopressin orally at bedtime, generally using low doses. Self-imposed fluid restrictions before bedtime are not effective in reducing the nocturnal urine output in this condition. Nocturia is also more prevalent in association with a reduced bladder capacity. Antimuscarinic drugs are used in attempts to depress involuntary bladder contractions. Decreased nocturnal voided volumes in men and consequent increased nocturia may suggest difficulty in emptying the bladder or detrusor overactivity. alpha(1)-Adrenoceptor antagonists and 5alpha-reductase inhibitors are often used in men with symptoms indicative of benign prostatic hyperplasia, and one of their effects is reduction of nocturia. In women, estrogen deficiency, a common consequence of the menopausal transition, causes atrophic changes within the urogenital tract. Consequently, such women are more disposed to having urogenital symptoms, among them nocturia. This review emphasises the importance of correctly diagnosing and treating nocturia in elderly patients. This will improve patients' sleep and, in turn, reduce their risk of fall injuries and the associated detrimental consequences, thereby improving patients' health and quality of life.

A bladder-cooling reflex in the anaesthetised guinea-pig: A model of the positive clinical ice-water test

Introduction: In patients with detrusor hyperreflexia, intravesical instillation of ice-cold water results in the development of involuntary bladder contractions at volumes less than normal cystometric capacity. This is referred to as a positive ice-water test (+IWT) and can be reversed by vanilloid receptor agonists and potentiated by menthol. The present study was designed to investigate the existence of an analogous cooling reflex in the guinea-pig bladder that could be used as a small animal model in order to test the effects of drugs on the reflex. Methods: Bladder pressure and external urethral sphincter electromyogram (EUS EMG) were recorded in α-chloralose/urethane anaesthetised guinea-pigs during rapid infusion of cold or warm saline into the bladder with or without prior intravesical exposure to menthol or resiniferatoxin (RTX). Results: The mean control micturition threshold volume (TV) of 2.58 ml at 38 °C was reduced to 1.52 ml in response to saline infusion at 3 °C ( P = 0.001). The cold-induced reduction in TV was reproducible during several subsequent repeat infusions at 38 °C and 3 °C and was accompanied by decreases in bladder voiding pressure. The duration of the micturition reflex was markedly increased following cold compared with warm saline infusion (mean 24.5 s at 3 °C, 10.2 s at 38 °C, P = 0.001) and was associated with oscillations in bladder pressure and concomitant bursting activity in the EUS EMG. During step-wise decreases in infusate temperature from 38 °C to 23 °C, 15 °C, 7 °C and 3 °C, the threshold infusate temperature to elicit a significant reduction in TV was 15 °C. The reduction in TV at 3 °C was potentiated by intravesical infusion of 0.6 mM menthol whilst intravesical infusion of 500 nM RTX reversed the reduction in TV at 3 °C. Discussion: These data suggest that a bladder-cooling reflex is present in the anaesthetised guinea-pig and represents a useful small animal model of the clinical +IWT.

Assessment of urodynamic bladder behavior on filling with solutions representing physiological extremes of urinary osmolarity

Verify if there is any difference in sensitive and motor bladder response in the presence of solutions with different osmolarities, simulating physiological extremes of urinary osmolarity. Thirty-three patients (24 men and 9 women) with mean age of 46.4 years (8 to 87 years) took part in this study. They were all subjected to 2 consecutive urodynamic examinations. In each exam, the vesical filling was accomplished by using a hyperosmolar (1000 mOsm/L) or hypo-osmolar (100 mOsm/L) sodium chloride solution in similar speed. The sequence in which each solution was instilled was determined by a double blind draw. The urodynamic results obtained from the infusion of both solutions were compared, regardless the sequence of administration. Fifteen patients (45.4%) showed detrusor hyperactivity, 12 of whom with neurological antecedents. The mean age of those with detrusor hyperactivity was 45.8 years, against 46.9 for those without hyperactivity. The infusion of the hyperosmolar/hypo-osmolar solution generated the following results, when comparing patients without vs. with detrusor hyperactivity: initial sensation of vesical filling (mL): 167.5/159.2 vs. 134.9/157.3 (p > 0.05); volume of occurrence of the first involuntary bladder contraction (mL): 163.9/151.9 (p > 0.05); detrusor micturition pressure (cm H2O): 24.0/24.4 vs. 13.8/27.5 (p > 0.05). The vesical filling with solutions simulating extreme urinary osmolarities, accomplished with similar speed and without previous identification, did not likewise alter the sensitive and motor urodynamic behavior in the current study.

The effects of α1A‐adrenoceptor antagonists on the urethral perfusion pressure of the female rat

To assess the effects of alpha(1A)-adrenoceptor antagonists on urethral perfusion pressure (UPP) in the female rate and their therapeutic potential for treating female bladder outlet obstruction (BOO). A cannula was inserted into the femoral arteries of female rats to administer tamsulosin (group I), doxazosin (group II) or phentolamine (group III) and to monitor systemic blood pressure. Tamsulosin was also administered to male rats (group IV). UPP and vesical pressures (Pves) were monitored using a triple-lumen catheter. After administration of tamsulosin to group I the frequency of bladder contractions decreased significantly and the duration of minimal urethral relaxation with high-frequency oscillations (HFOs) was significantly prolonged. Except for mean arterial blood pressure (MAP), none of the variables in group I differed significantly from those in group II and group III. The change in MAP after tamsulosin treatment was significantly lower than after doxazosin or phentolamine. Except for the maximum Pves, which was significantly higher in males (group IV) than in females of group I, the UPP and Pves curves of male rats were similar to those of females before giving tamsulosin. The prolonged frequency and duration of HFO in group IV (with tamsulosin) were significantly different from those of females. The alpha(1A)-adrenergic receptor may be a functional subtype in the female rat urethra. alpha(1A)-adrenoceptor antagonists prolonged the duration of HFOs and decreased the frequency of involuntary bladder contraction. It is possible that treatment with alpha(1A)-adrenoceptor antagonists would not only improve obstructive symptoms, but also ameliorate irritative symptoms by prolonging HFOs and the frequency of involuntary bladder contractions.