Changes In Intravesical Pressure Research Articles

Does altered myogenic activity contribute to OAB symptoms from detrusor overactivity? ICI-RS 2013.

To highlight novel experimental approaches that test if the Myogenic Hypothesis remains viable as a contributor to the aetiology of detrusor overactivity. To summarise the conclusions of a workshop held under the auspices of ICI-RS in 2013. Several theories may explain the pathology of detrusor overactivity and include a myogenic theory with fundamental changes to detrusor muscle excitation-contraction coupling. The isolated bladder displays micromotions that do not normally translate into significant changes of intravesical pressure. However, their amplitude and frequency are altered in animal models of bladder dysfunction. The origin of micromotions, if they generate significant changes of intravesical pressure and contribute to urinary tract sensations remain unanswered. Within the myocyte, changes to contractile protein phosphorylation through accessory proteins and cytoplasmic regulatory pathways occur in lower urinary tract pathologies associated with detrusor overactivity. Furthermore, myocytes isolated from overactive human bladders generate greater spontaneous activity, but a complete description of changes to ionic currents remains to be characterised. Finally, several growth factors, including mechano-growth factor, are released when bladder wall stress is increased, as with outflow obstruction. However the phenotype of the transformed detrusor myocytes remains to be measured. A number of lines of evidence suggest that the Myogenic Hypothesis remains viable as a contributor to detrusor overactivity.

MP17-06 ROLE OF SPINAL α2-ADRENOCEPTORS AND IMIDAZOLINE RECEPTORS IN THE CONTROL OF VOIDING AND CONTINENCE REFLEXES IN CONSCIOUS RATS

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology1 Apr 2014MP17-06 ROLE OF SPINAL α2-ADRENOCEPTORS AND IMIDAZOLINE RECEPTORS IN THE CONTROL OF VOIDING AND CONTINENCE REFLEXES IN CONSCIOUS RATS Akira Furuta, Shouji Kimura, Mariko Honda, Takehito Naruoka, Nozomu Furuta, Yasuyuki Suzuki, Shin Egawa, and Naoki Yoshimura Akira FurutaAkira Furuta More articles by this author , Shouji KimuraShouji Kimura More articles by this author , Mariko HondaMariko Honda More articles by this author , Takehito NaruokaTakehito Naruoka More articles by this author , Nozomu FurutaNozomu Furuta More articles by this author , Yasuyuki SuzukiYasuyuki Suzuki More articles by this author , Shin EgawaShin Egawa More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.527AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES α2-Adrenoceptor (AR) agonists and antagonists additionally have varying affinity for imidazoline receptors (I-Rs). It has been reported that intrathecal (i.t.) administration of α2-AR agonists such as dexmedetomidine induces the sedative and analgesic effects and that i.t. application of I1-R agonists such as clonidine has the hypotensive effect. In this study, we investigated the role of spinal α2-ARs, I1-Rs and I2-Rs in the control of voiding and continence reflexes in rats. METHODS Under isoflurane anesthesia, a polyethylene catheter was implanted at the L6/S1 levels of the spinal cord 3 days before the examination using female Sprague-Dawley rats. Changes in intravesical pressure, urinary leak point pressure (LPP) or blood pressure (BP) were examined in an awake condition when 0.3, 3, 30nmol of clonidine (I1-R and α2-AR agonist), idazoxan (I1-R antagonist, I2-R ligand and α2-AR antagonist), benazoline (I2-R ligand), B-HT933 (α2-AR agonist) or yohimbine (α2-AR antagonist) were respectively and cumulatively applied i.t. with 30min intervals (each n=5). Cystometrograms were recorded during intravesical infusion (0.04ml/min) of saline, and LPPs were measured as the intravesical pressure causing fluid leakage from the urethral orifice during 3ml/min saline infusion into the bladder. Mean BPs were also monitored via the carotid artery. RESULTS Both clonidine and B-TH933 dose-dependently increased mean threshold pressures inducing reflex bladder relaxation, resulting in total incontinence in 3 of 5 by the application of 30 nmol clonidine whereas both idazoxan and yohimbine significantly decreased mean threshold pressures. Clonidine significantly decreased both mean LPPs and BPs although idazoxan significantly increased both mean LPPs and BPs. Benazoline also increased mean BPs significantly. There were no significant differences in other parameters. CONCLUSIONS These results suggest that sensory transduction from the bladder (represented by threshold pressure changes) are in part mediated by α2-ARs in the spinal cord and that urethral smooth and/or striated muscle sphincter (represented by LPP changes) are partly controlled by spinal I1-Rs. These findings would be useful to develop the new treatments for lower urinary tract dysfunction. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e137 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Akira Furuta More articles by this author Shouji Kimura More articles by this author Mariko Honda More articles by this author Takehito Naruoka More articles by this author Nozomu Furuta More articles by this author Yasuyuki Suzuki More articles by this author Shin Egawa More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Selective innervation of sacral anterior rootlets to micturition and erection function in rats

To investigate the selective innervation of sacral anterior rootlets to micturition and erection function in SD rats. Forty male SD rats of clean grade, aged 6 weeks old, were selected. Ten rats received a retrograde nerve tract tracing study. Thirty rats were chosen for an electro-physiological study. The L6, S1 spinal cord segment anterior rootlets of anesthetic rats were electrostimulated respectively. The intravesical pressure, urethral perfusion pressure and intracavernous pressure were recorded simultaneously and innervation effectiveness was analyzed. CB-HRP labeled neurons were observed mainly in L6 and S1 spinal cords. When some anterior rootlets of L6 and S1 were electrostimulated, the intravesical pressure rose gradually, but the urethral perfusion pressure and the intracavernous pressure curve changed slightly; when other rootlets of the same anterior root were stimulated, the urethral perfusion pressure could reach the peak; while others were stimulated, the intracavernous pressure rose quickly, but there were no great changes in intravesical pressure and urethral perfusion pressure. Some other rootlets might lead to the simultaneous changes of 2 or 3 above-mentioned pressures. The innervations of L6 and S1 anterior rootlets to rats' bladder detrusor, external urethral sphincter and penile cavernous body are significantly distinct. Different rootlets may be distinguished by microanatomy and electrostimulation.

Fourier analysis of electrical impedance variations in urinary bladder during changes of intravesical pressure

Original hardware and software system was used to record and analyze the variations of electrical impedance of the urinary bladder in narcotized rats (n=7) at rest, during instillation of physiological saline into the bladder resulted in elevation of intravesical pressure, and during subsequent urination accompanied by intravesical pressure release. Fourier analysis of impedance variations revealed three periodic components with the frequencies of heartbeat, respiration, and the Mayer wave (~0.1 Hz). In resting bladder, the amplitude of Mayer and respiratory spectrum peaks were high, and they increased to a different extent during physiological elevation of intravesical pressure, while a small cardiac peak did not changed significantly and tended to decrease at high intravesical pressure. Urination released intravesical pressure and restored all the peaks to the resting level. It is hypothesized that Mayer and respiratory bioimpedance oscillations of urinary bladder are neural in origin, while the cardiac peak is mainly determined by hydrodynamic arterial pulsations. The novel method can assess vesical circulation and its neural control at various phases of bladder activity.

Relaxation Effect of Phosphodiesterase-5 Inhibitor on the Animal Bladder and Prostatic Urethra: in vitro and in vivo Study

Aim: To assess the relaxation effect of the phosphodiesterase-5 inhibitor udenafil on the bladder and prostatic urethra and its therapeutic potentials for benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS). Methods: For the in vitro study, muscle strips from urinary bladder and urethra were prepared from male New Zealand rabbits. The strips were mounted in organ baths and connected to force transducers. After stabilization, maximal tissue contractions were obtained by the addition of phenylepinephrine for urethra strips and carbachol for bladder strips. When the contraction was stabilized, a dose-response curve of udenafil was constructed. For the in vivo study using adult male Sprague-Dawley rats, changes of intravesical pressure and urethral perfusion pressure after intraarterial administration of udenafil were monitored. Results: Udenafil significantly relaxed the bladder and urethra strips in a dose-dependent manner. At 10^–3 M, udenafil induced a significant relaxation of the bladder strips by 37.3% and of the urethra strips by 44.0%. In the in vivo study, the intercontraction interval was significantly prolonged (p < 0.01) and the duration of urethral relaxation with high-frequency oscillations was significantly prolonged (p < 0.01) after udenafil. Conclusions: Udenafil had relaxant effects on the bladder and prostatic urethral smooth muscle. Clinically, udenafil could be applied as an effective treatment for BPH/LUTS.

Substantial detrusor overactivity in conscious spontaneously hypertensive rats with hyperactive behaviour

The spontaneously hypertensive rat (SHR) is a useful model for studying the mechanisms of detrusor overactivity (DO). However, owing to their confounding phenotypic characteristics of hyperactive behaviour, there could be some problems with the interpretation of cystometric data, which is significantly confused by abdominal straining (AS), causing changes in intravesical pressure (IVP). IVP and intra-abdominal pressure (IAP) were recorded simultaneously to evaluate true DO in conscious healthy male SHRs and Wistar/ST (Wistar) rats. Intravesical pressure rises (IVPRs), defined as increments that exceeded 2 cmH(2)O from baseline, were counted, and those that were caused by AS or DO were determined according to the presence of simultaneous changes in IAP. Compared with Wistar rats, SHRs had a shorter filling phase (p<0.01) and greater frequency of IVPRs (p<0.01). SHRs, but not Wistar rats, showed DO. The substantial DO represented up to 76% of total IVPRs, with the remainder caused by AS. The amplitude (p<0.05) but not the frequency of AS (p>0.05), was higher in SHR than Wistar rats. In conscious SHRs, variations in IAP due to hyperactive behaviour may cause misinterpretation of pressure parameters and result in false reports of DO. Thus, simultaneous registration of IAP and IVP is needed for accurate recording of substantial DO in these animals.

The Integrative Physiology of the Bladder

Normal bladder function is complex, resulting from the co-operative interaction of numerous regulatory cell types, of which the interstitial cells and the peripheral neurones are particularly interesting. Collectively, these comprise the myovesical plexus, which appears to confer structural and functional characteristics on the bladder loosely akin to those of the gut. These include functional modularity, which gives rise to the potential for localised and propagating peristalsis-like movements in the bladder wall according to the prevailing physiological conditions. Localised modular activity during filling may contribute to normal generation of sensation and exaggerated modular activity may give rise to urinary urgency. Enhanced co-ordination of modular activity occurs in various models of detrusor overactivity; it leads to surges of contraction over a large part of the bladder wall, generating phasic changes in intravesical pressure. During voiding, the myovesical plexus sustains detrusor contraction at the behest of the brainstem, monitoring state of bladder fullness as it does so, as a guide to the required duration for which it has to keep up the effort. Accordingly, the bladder wall itself may house structures which render the bladder the effector level in a hierarchy of lower urinary tract regulation. Dysfunction in these vital regulatory structures is an underestimated factor in the pathophysiology of clinical bladder problems.

Cholinergic activation of phasic activity in the isolated bladder: possible evidence for M3‐ and M2‐dependent components of a motor/sensory system

To analyse pressure changes induced by muscarinic agonists on the isolated bladder in order to examine whether there are different responses representing different components of a motor/sensory system within the bladder wall. Whole isolated bladders from 19 female guinea-pigs (280-400 g) were used. A cannula was inserted into the urethra to monitor intravesical pressure and the bladder was suspended in a heated chamber containing carboxygenated physiological solution at 33-36 degrees C. Initially, the responses to the cholinergic agonists, arecaidine but-2-ynyl ester tosylate and carbachol were assessed. Then, in an attempt to identify the muscarinic receptor subtypes involved, the effects of selective muscarinic antagonists on the arecaidine-induced bladder responses were assessed. The antagonists used were the relatively M(3)-selective 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) and darifenicin, and relatively M(2)-selective AFDX-116. All drugs were added to the solution bathing the ablumenal surface of the bladder. The whole bladders exposed to cholinergic agonists respond with complex changes in intravesical pressure. Immediately after application of the agonist there was a burst of high frequency transient contractions. During continued application of agonist the frequency of the transients decreased and their amplitude increased. Thus, there appear to be two components to the response: an initial fast phase and a later slow component. The maximum frequency of the initial burst increased with increasing concentrations of agonist. By contrast, the frequency of the transients in the steady state showed little dependence on agonist concentration. There were quantitative differences between the responses to arecaidine and carbachol. Arecaidine was less effective in generating the initial burst of high-frequency activity and the transients were significantly larger. At low dose, arecaidine was more effective in producing the large transients in the steady state. Pre-exposure of the bladder to 4-DAMP (0.1-10 nM) or darifenicin (0.1-10 nM) significantly reduced the frequency of the initial burst of activity; 0.3 nM 4-DAMP reduced the frequency by half. In this concentration range, 4-DAMP reduced the amplitude of the initial transients but did not affect the frequency of the transients in the steady state. There were similar results with darifenicin. However, darifenicin was less effective in reducing the amplitude of the initial transients. By contrast, ADFX-116 had little effect on the frequency of the initial transients but did reduce amplitude; 300 nM AFDX-116 was needed to reduce the frequency of the initial burst by half. This analysis suggests that there are different but interrelated mechanisms in the isolated bladder contributing to complex contractile activity. Three components can be identified: a mechanism operating during voiding to produce a global contraction of the whole bladder and two mechanisms, pacemaker and conductive, involved in generating and propagating local contractions in the bladder wall. The pacemaker component is more sensitive to darifenicin and 4-DAMP than to AFDX-116 suggesting that the underlying processes rely predominantly on M(3) receptors and less so on M(2) (M(3) > M(2)). The phasic activity in the later stages is less affected by M(3) antagonists and might therefore involve predominantly M(2) receptors (M(2) > M(3)). The potential importance of these results in terms of the general physiology and pharmacology of the bladder is discussed.

Comparative in vivo uroselectivity profiles of anticholinergics, tested in a novel anesthetized rabbit model

The aim of this study was to describe a new experimental animal model for simultaneous measurement of carbachol-induced increase in intravesical pressure and salivary secretion in rabbits. Further, we also compared the in vivo potency and urinary bladder versus salivary gland selectivity profiles of Oxybutynin, Tolterodine, Solifenacin and Darifenacin. The intravesical pressure and salivary secretion were evoked by intra-arterial injection of carbachol (1.5 microg/kg). The carbachol-induced increase in intravesical pressure and salivation was simultaneously recorded before and after increasing doses of test drugs administered intravenously. The basal mean changes in intravesical pressure and salivation subsequent to carbachol administration were in the range of 6.7-7.5 mm Hg and 0.5-0.7 g respectively. Repeated administration of vehicle did not elicit any appreciable changes in intravesical pressure and salivary secretion to carbachol administration from the basal values till 3 h. All the test drugs exhibited a dose-dependent inhibition of carbachol-induced increase in intravesical pressure and salivary secretion. Darifenacin demonstrated a greater potency compared to other muscarinic receptor antagonists for inhibiting carbachol-induced increase in intravesical pressure. It also exhibited functional selectivity for the urinary bladder versus salivary gland. In contrast, Oxybutynin was functionally more selective in inhibiting carbachol-induced increase in salivary secretion. The observed urinary bladder versus salivary selectivity values were 0.6+/-0.2, 1.1+/-0.2, 1.7+/-0.5, and 2.3+/-0.5 for Oxybutynin, Tolterodine, Solifenacin and Darifenacin respectively. These results suggest that the functional selectivity of muscarinic receptor antagonists between urinary bladder and salivary glands can be readily detected in this model. Thus rabbits may represent a useful animal model for evaluating putative bladder selective muscarinic receptor antagonists for the treatment of overactive bladder.

Cardiovascular and Intravesical Pressure Responses during Natural Micturition in Conscious Rats

Urinary bladder distension is known to influence the cardiovascular system under a pathophysiological condition such as spinal cord injury, hypertension, and arteriosclerosis. A reflex due to bladder distension and/or contraction is considered as one reason for the cardiovascular disturbance associated with micturition. However, it has remained unknown how much intravesical pressure (IVP) rises during micturition in daily life and to what extent mean arterial blood pressure (MAP) and heart rate (HR) respond at that time. To answer these questions, we attempted to examine the direct changes in IVP, MAP, and HR during natural micturition in freely moving conscious rats. IVP increased from the baseline value of 4 +/- 0.2 mmHg to 14 +/- 0.5 mmHg during natural micturition. Although MAP and HR began to increase before micturition, the increases in MAP and HR became significant 1-4 s before its onset. The peak increases in MAP and HR (7 +/- 0.8 mmHg and 14 +/- 3 beats/min, respectively) were delayed by 2 s from the peak IVP. Following an administration of xylocaine into the urinary bladder, the increases in MAP and HR during micturition were significantly blunted to 5 +/- 2 mmHg and 8 +/- 3 beats/min, although IVP increased the same as it did during micturition without xylocaine. Moreover, the relationship between IVP and MAP or HR during natural micturition resembled that between IVP and the vesico-cardiovascular reflex responses during isovolumic bladder contraction in anesthetized rats. Therefore it is concluded that natural micturition in freely moving conscious rats accompanies the significant cardiovascular responses despite a limited increase in intravesical pressure, to which a reflex from the urinary bladder may substantially contribute.

Autonomous activity in the isolated guinea pig bladder.

Phasic changes in pressure have been reported to occur in the bladder which are not associated with micturition. Spontaneous intravesical pressure changes can be recorded from bladders in vitro or bladders in vivo isolated from the central nervous system suggesting that the bladder itself is capable of autonomous activity. Experiments using isolated cells and muscle strips indicate that the smooth muscle can generate spontaneous activity. Whether this is the origin of phasic changes in the intact organ remains unknown. The present study set out to establish the presence and characteristics of autonomous activity in the isolated guinea pig bladder. Multiple-point motion analysis and concurrent intravesical pressure recording were used to identify and quantify spontaneous and evoked activity. Highly complex autonomous activity was observed in unstimulated bladders. This activity comprised localised micro-contractions in single or multiple discrete regions, waves of activity and micro-stretches. Low-amplitude phasic 'micro-transients' were seen in the intravesical pressure trace in association with micro-contractions. Incremental increases in the intravesical volume recruited additional areas of activity. Atropine and tetrodotoxin had no effect on the micro-transients or micro-contractions. Exposure to the muscarinic agonist arecaidine (10-300 nM) initially increased the incidence of micro-contractions which subsequently became co-ordinated into phasic pressure rises and contraction waves, interspersed with periods of total quiescence. The findings describe the generation and co-ordination of autonomous activity in the bladder wall and also demonstrate complex phasic activity. This approach has shown the importance of assessing the integrative properties of the entire organ in studies of the physiology and patho-physiology of the bladder.

A NEW APPROACH TO RECORDING THE ELECTROMYOGRAPHIC ACTIVITY OF DETRUSOR SMOOTH MUSCLE

Extracellular recordings from the whole intact mammalian bladder of the electrical events leading to contraction of the organ have been elusive for almost 50 years despite the widespread potential applications of such a technique. The principal problem is the need to isolate the small real signals reflecting membrane depolarization from the large electromechanical artifact generated as the organ contracts. In this preliminary study we determined whether electrical signals may be isolated and verified as biological using extracellular bipolar reversible suction electrodes. Six whole excised guinea pig bladders were mounted in an especially constructed organ bath. Electrical activity resulting from nerve stimulation of the organ was recorded using a novel 10 bipolar Pt/PtCl suction electrode simultaneously with changes in intravesical pressure. Mechanical and pharmacological control experiments were performed to determine the true origin of these signals. A predominantly biphasic electrical signal of a mean amplitude plus or minus standard deviation of 647 plus or minus 301 microV. and a mean duration of 293 plus or minus 51 milliseconds was consistently recorded from the serosal surface of all guinea pig bladders. In all cases the electrical signal and mechanical response to stimulation were completely abolished by 1 microM. tetrodotoxin. The signal always preceded any change in intravesical pressure. It was sensitive to changes in the CaCl2 concentration of the superfusate, abolished by purinergic but not cholinergic neuromuscular blockade and independent of electromechanical artifact. In this preliminary report we describe a novel technique by which nerve mediated detrusor electrical activity leading to contraction of the whole intact guinea pig bladder may be isolated from artifact and verified as real. We hope that development of this technique may enable its application to the in situ human bladder. However, to our knowledge whether electromyographic activity may be recorded from human detrusor remains to be determined.

The effects of a selective noradrenaline reuptake inhibitor on the urethra: an in vitro and in vivo study.

To identify the effects of a selective noradrenaline reuptake inhibitor (venlafaxine) on urethral perfusion pressure (UPP) in rabbits and rats, and thus assess its therapeutic potential for treating stress urinary incontinence. Strips of bladder and proximal urethra were prepared from female New Zealand White rabbits. Each strip was electrically stimulated and the contractile responses of controls strips compared with those after pretreatment with venlafaxine (100 micromol/L). In separate experiments using 80 adult female Sprague-Dawley rats (250-300 g), changes in intravesical pressure and UPP after the intra-arterial and intra-urethral administration of phenylephrine, phentolamine, fluoxetine and venlafaxine were monitored using double-lumen catheters. Pretreatment with venlafaxine significantly decreased the contraction of bladder strips (P=0.01) and significantly increased the contraction of urethral strips (P=0.008). In vivo, phenylephrine administered by both routes significantly increased UPP (P=0.02); phentolamine (arterial) significantly decreased UPP (P=0.001); fluoxetine (arterial) had no effect on UPP, and venlafaxine (both routes) significantly increased UPP (both P<0.001). The intravesical pressure was not changed significantly in any animal. Venlafaxine effectively increased UPP both in vitro and in vivo; these results imply that venlafaxine may be useful for treating stress urinary incontinence, by increasing the UPP.

ELECTROMOTIVE ADMINISTRATION OF INTRAVESICAL BETHANECHOL AND THE CLINICAL IMPACT ON ACONTRACTILE DETRUSOR MANAGEMENT:: INTRODUCTION OF A NEW TEST

It is often difficult to determine the functional status of the detrusor muscle in patients with detrusor areflexia. We performed a clinical study to establish a test defining residual detrusor capacity in such patients. In phase 1, 5 controls with detrusor areflexia were tested with an intravesical instillation of 20 mg. bethanechol in 150 cc of sodium chloride 0.3% with and without 20 mA. of pulsed current applied via an electrode catheter through the saline. Cystometry simultaneously recorded intravesical pressure changes. In phase 2, 45 patients with detrusor areflexia were tested with electromotive administration of intravesical bethanechol. In phase 3, 25 mg. bethanechol given orally once daily were prescribed for 15 patients and voiding control was assessed after 6 weeks of therapy. Neither bethanechol without current nor current through saline only led to increased intravesical pressure. However, we noted a mean pressure increase of 34 cm. water during the electromotive administration of bethanechol in 24 of 26 patients with areflexia and neurological disease compared to only 3 cm. water in 3 of 11 with a history of chronic bladder dilatation. Oral bethanechol restored spontaneous voiding in 9 of 11 patients who had had a positive response to the electromotive administration of bethanechol, whereas all 4 without a pressure increase during the electromotive administration of bethanechol did not void spontaneously. Electromotive administration of intravesical bethanechol identifies patients with an atonic bladder and adequate residual detrusor muscle function who are candidates for restorative measures, such as oral bethanechol and intravesical electrostimulation. Those who do not respond to the electromotive administration of bethanechol do not benefit from oral bethanechol and are candidates for catheterization.

A new approach to bladder augmentation in children: seromuscular enterocystoplasty.

To report the use of seromuscular enterocystoplasty (SE) combined with detrusorectomy, in children. Between 1993 and 1998, SE was performed in 10 children (aged 10-17 years) with a spastic neurogenic bladder resulting from spinal trauma. Before surgery all children were incontinent and despite anticholinergic medication and clean intermittent catheterization, their bladder capacity was 60-100 mL and their intravesical pressure 40-60 cmH2O. Before surgery, the mean end-filling intravesical pressure was 47.7 cmH2O and the mean bladder capacity 82.9 mL. At 3 months after surgery the mean end-filling intravesical pressure was decreased to 21.1 cmH2O and the mean bladder capacity increased to 319.6 mL. One patient (a 14-year-old girl) had urinary retention soon after surgery and has since used clean intermittent catheterization. The other children were able to void successfully using the Valsalva manoeuvre; none were incontinent. All patients were followed and there were no changes in intravesical pressure and bladder capacity. In providing most of the desired features of an ideal augmentation segment, SE is a good and effective method of bladder augmentation.

Smooth muscle fatigue due to repeated urinary bladder neurostimulation: an in vivo study.

The presented study investigates the influence of different pause lengths between two consecutive stimulations of the S3 roots on intravesical pressure during bladder neurostimulation. In eight male foxhounds (aged 7-18 months), laminectomy and placement of a modified Brindley electrode were performed. In four series with different pause lengths between two consecutive stimulations (1, 3, 5, and 15 min), the maximum intravesical pressure was measured during stimulation. The changes in intravesical pressure were registered in these four series, each series with six stimulations. A 15-min interval elapsed before the commencement of each series. In the series with a pause length of 15 min, the consecutive stimulations did not result in significant changes in maximum intravesical pressure. In the 5-min series, a significant decrease in intravesical pressure was not observed after the third stimulation. In the 3-min series, a significant decrease was seen at almost every stimulation (average decrease of 3.8% per stimulation) and in the 1-min series, a significant decrease was also observed at almost every stimulation (average decrease of 5.9% per stimulation). The results of repeated bladder neurostimulation demonstrate that the maximum intravesical pressure is dependent on the pause length between two consecutive stimulations. The detrusor muscle showed reversible and short-lived signs of fatigue. This implies the importance of a minimum 5-min interval between two subsequent stimulations. A pause length <5 min leads to a falsification of the results and thus to lower validity of the investigation.

A psychophysical study of discomfort produced by repeated filling of the urinary bladder

Psychophysical studies were performed in 10 healthy, female volunteers using urinary bladder distension (UBD) as a visceral stimulus. Stimulus methodology was similar to that used clinically for obtaining cystometrograms with a fixed-rate (100 cc/min normal saline) filling of the urinary bladder, occasional pauses and simultaneous measure of bladder pressure using a catheter–transducer assembly. During bladder filling, subjects were asked to report sensations by verbal report and by using an electronic, hand-held, visual-analog-scale device. Sensations evoked by UBD were generally localized to the suprapubic region. UBD produced cardiovascular responses which increased with repeated trials. Sensation intensity increased with repeated UBDs as indicated by global pain ratings. Intravesical pressure and volume correlated with sensation intensity. The volume of distending fluid needed to produce a report of discomfort was highly variable from trial to trial and did not change significantly with repeated UBDs. The intravesical pressure which produced a report of discomfort was less variable and significantly decreased with repeated UBDs. The change in intravesical pressure and volume needed to produce discomfort was inversely correlated with initial intravesical pressure measures. Similar to findings in other organ systems, these findings demonstrate that repeated presentations of a visceral stimulus may lead to an increase in physiological and perceptual responses to pain.

The Effects of Aging on the Rat Bladder and Its Innervation.

1) Measurements of the cystometrogram, of the responsiveness of bladder muscle to pelvic nerve efferent stimulation and of the sensitivity of the pelvic nerve afferents to pressure and volume during distensions have been made in the bladders of young adult (2-3 months) and aged (26-29 months) rats, anesthetized with mixtures of urethane and chloralose. 2) The pressure-volume relationship differed in young adult and aged rats. The bladders of the aged rats held up to nearly six times the volume of the young animals, and these volumes were accommodated at lower pressures in the aged animals. The pressure at which micturition contractions appeared was similar in young adult and aged animals. 3) The passive pressure associated with each of a series of distending volumes was recorded when a pelvic nerve was cut unilaterally. The distal cut end of this cut pelvic nerve was stimulated for 10 s at 20 Hz, using square wave pulses of 10 V and 1.0 ms. The active pressure-volume relationship was constructed from this data. Both the active and the passive relationships were shifted to the right in the aged animals, and it was evident that aging was associated with a reduction in the maximal pressure generated during pelvic nerve stimulation. Also the change in intravesical pressure induced by bladder contraction was less in aged animals. 4) The most sensitive mechanoreceptor afferents appear to have pressure and volume thresholds that do not change significantly during aging. While the distension-sensitive afferents in the pelvic nerve appear to have a similar sensitivity to intravesical pressure in young adult and aged rats, they were less able to monitor volume in the aged animals. The stimulus response relationship for volume was often less steep in the aged animals. 5) In this study, aging was shown to be associated with a large increase in bladder volume and a reduced sensitivity of pelvic nerve afferents to volume, and a reduced ability to raise bladder pressure during contraction of bladder smooth muscle. The changes in bladder function associated with aging are discussed.

Effect of naftopidil on urethral obstruction in benign prostatic hyperplasia: Assessment by urodynamic studies

Thirty-two patients with voiding dysfunction attributable to symptomatic benign prostatic hyperplasia were treated with naftopidil, an alpha 1-blocker, at doses of 25-75 mg/day for 4-6 weeks. The efficacy of the drug was assessed from the changes in urinary symptoms and urodynamic data. Total symptom scores were significantly reduced after treatment (P < 0.001). Average flow rate and maximum flow rate were significantly increased (P < 0.001 and P < 0.001, respectively), and residual urine volume, residual urine rate (ratio of residual urine volume/sum of voided volume and residual urine volume), and maximum urethral closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05, respectively) reduced, and at bladder capacity, the first desire to void was significantly (P < 0.05) increased. The pressure/flow study demonstrated no changes in intravesical pressure at maximum flow, but a significant (P < 0.05) reduction in minimum urethral resistance. A mild side effect (dizziness) was noted in one patient (3.3%), which soon disappeared after the dose was decreased. The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was evaluated to be promising in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia.

Elimination of the influence of intravesical pressure on the micturitional urethral pressure profile by calculation of urethral cross-sectional area: an experimental study.

To determine whether it is possible to eliminate the influence of intravesical pressure on the pressure drop recorded between the bladder and prostatic urethra during the micturitional urethral pressure profile (MUPP). An experimental study using an artificial bladder/urethral model and computerized urethral pressure profile measurement system. By simultaneous measurement of the flow rate and MUPP it is possible to calculate a theoretical cross-sectional area, based on Griffiths' theory of flow through distensible tubes. The calculated cross-sectional area for a given constriction remains the same despite changes in the driving pressure. The effect of changes in intravesical pressure on the MUPP can be eliminated by calculation of the urethral cross-sectional area. This parameter forms part of the Schäfer model of obstruction and this technique may therefore be useful in quantifying bladder outlet obstruction.