[Post-obstructive polyuria. Pathophysiological analysis of a case]. / Poliuria post-obstructiva. Análisis fisiopatológico de un caso.

The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.

Interactive Effects of Perinatal BPA or DES and Adult Testosterone and Estradiol Exposure on Adult Urethral Obstruction and Bladder, Kidney, and Prostate Pathology in Male Mice.

Obstructive voiding disorder (OVD) occurs during aging in men and is often, but not always, associated with increased prostate size, due to benign prostatic hyperplasia (BPH), prostatitis, or prostate cancer. Estrogens are known to impact the development of both OVD and prostate diseases, either during early urogenital tract development in fetal-neonatal life or later in adulthood. To examine the potential interaction between developmental and adult estrogen exposure on the adult urogenital tract, male CD-1 mice were perinatally exposed to bisphenol A (BPA), diethylstilbestrol (DES) as a positive control, or vehicle negative control, and in adulthood were treated for 4 months with Silastic capsules containing testosterone and estradiol (T+E2) or empty capsules. Animals exposed to BPA or DES during perinatal development were more likely than negative controls to have urine flow/kidney problems and enlarged bladders, as well as enlarged prostates. OVD in adult T+E2-treated perinatal BPA and DES animals was associated with dorsal prostate hyperplasia and prostatitis. The results demonstrate a relationship between elevated exogenous estrogen levels during urogenital system development and elevated estradiol in adulthood and OVD in male mice. These findings support the two-hit hypothesis for the development of OVD and prostate diseases.

Anterior Urethral Valve - A Commonly Misdiagnosed Entity in Adolescent Boys.

Anterior urethral valves are a rare cause of obstructed voiding in adolescent children and are often unheard by adult urologists. In this case report, we discuss the management of two adolescent patients who were referred to us with obstructive voiding symptoms with a diagnosis of neurogenic bladder and posterior urethral valves respectively but on evaluation were found to have anterior urethral valves. This article highlights the need for considering anterior urethral valve as an important differential diagnosis in children and adolescents presenting with obstructive voiding symptoms so as to avoid delay in diagnosis and management in young boys.

Effect of Early Oxybutynin Treatment on Posterior Urethral Valve Outcomes in Infants: A Randomized Controlled Trial.

PURPOSE: We studied the effect of oxybutynin on bladder and upper urinary tract outcomes in infants following posterior urethral valve ablation. MATERIALS AND METHODS: Patients younger than 12 months old who had undergone primary endoscopic valve ablation for posterior urethral valves were screened for eligibility. Patients who had undergone urinary diversion or had other conditions that could affect lower urinary tract function were excluded. Study patients were randomized to either oxybutynin (0.2 mg/kg 3 times daily) until toilet training or active observation. The study end points were serum creatinine, estimated glomerular filtration rate, hydronephrosis improvement, vesicoureteral reflux resolution, febrile urinary tract infection and toilet training. RESULTS: A total of 49 infants (24 receiving oxybutynin and 25 undergoing observation) were enrolled between December 2013 and September 2015 and completed at least 1 year of followup. Oxybutynin was discontinued before toilet training in 5 patients due to facial flushing in 2, bladder and upper tract dilatation in 2, and cognitive changes in 1. After a median followup of 44.2 months (range 12 to 57.6) median serum creatinine and estimated glomerular filtration rate were not significantly different between the groups (p=0.823 and p=0.722, respectively). Renal units in the oxybutynin group had a greater likelihood of hydronephrosis improvement (61.9% vs 34.8%, p=0.011) and resolution of vesicoureteral reflux (62.5% vs 25%, p=0.023). Febrile urinary tract infection (29.2% vs 40%, p=0.404), completion of toilet training (70.8% vs 76%, p=0.748) and age at toilet training (p=0.247) did not differ significantly between the oxybutynin and observation groups. CONCLUSIONS: Oxybutynin enhances hydronephrosis improvement and vesicoureteral reflux resolution following primary endoscopic valve ablation in infants but periodic monitoring is warranted.

Account for high flow rate-low detrusor pressure voids in female: Contribution of VBN model.

INTRODUCTION: Nomograms using the VBN model of women micturition allowed evaluating detrusor contractility (k) and urethral obstruction (U) from pressure-flow (PFs) recordings. While the model worked for most of the patients, an intriguing result, negative U value was observed for patients with high flow-low detrusor pressure (Qp voids). To explain that condition, our hypothesis was a weak urethral resistance to dilatation or increased expansibility (URD). METHODS: The area offered to the fluid at each point of the urethra (its dilatation) is a function of the time depending difference between inside and outside pressures. In the VBN model, this function is sigmoid-like, the same for all women. For Qp voids, Qrecorded was more higher than it would be with the recorded pressure (VBN analysis). So, modeling allowed computing abnormally increased urethral wall expansibility (URD) whose consequence would be an increased flow. RESULTS: Among 222 non-neurologic women referred for investigation of various lower urinary tract symptoms, 27 (mean age 66.3±11.4 y) had Qp void: Qmax=27±6mL/s; pdet.Qmax =7.5±4.7cm H2O. Mean URD value was .36±.67. Introduction of URD in a modeled analysis of urodynamic traces led to a good fitting between recorded and computed traces for the 27 Qp. CONCLUSION: Mathematical modeling of micturition allows proposing an explanation of the unexpected observations of Qp voids. They would be due to abnormal urethral wall elasticity. Despite major challenges measurement of this elasticity would be the next step. LEVEL OF EVIDENCE: 3.

Myocardial function in fetuses with lower urinary tract obstruction: Is there a cardiac remodeling effect due to renal damage?

OBJECTIVES: Cardiac remodeling due to renal dysfunction may have an impact on myocardial function (MF) of fetuses with lower urinary tract obstruction (LUTO). The aim was to identify possible differences in MF in LUTO fetuses compared with healthy controls and to look for interactions between urine biochemistry and MF indices. METHODS: This is a cohort study consisting of 31 LUTO fetuses and 45 healthy controls. Subgroups were generated according to intrauterine therapy (group 1: LUTO after therapy, group 2: LUTO without therapy at the time of examination, and group 3: controls). MF indices were measured using pulsed wave tissue Doppler imaging and M-mode. Furthermore, results of fetal urine biochemistry were gathered retrospectively. RESULTS: Among other findings, right ventricular (RV) e'/a' ratio was lower in group 1 compared with group 3 (p = .050). According to gestational age (GA) level-dependent analysis, RV isovolumetric relaxation time was significantly longer in group 2 compared with group 1 and group 3 at GA level 1 (19 wk of gestation). A significant positive correlation between RV e'/a' ratio and ß-2-microglobulin as well as α-1-microglobulin and potassium could be observed. CONCLUSION: We observed differences in MF and an association between ventricular filling pattern and renal protein secretion in LUTO fetuses. This can be interpreted as a sign of intrauterine cardiac remodeling.

Prenatal extravasation of urine seems to preserve renal function in boys with posterior urethral valves.

INTRODUCTION: A posterior urethral valve (PUV) may lead to extravasation of urine, resulting in prenatal ascites and/or perirenal urinoma. Extravasation has been presumed to act as a pop-off mechanism, preserving renal function, but previous reports addressing this presumption have been inconclusive. AIM OF STUDY: The present study compares renal function in patients with PUV with and without extravasation. MATERIAL AND METHODS: Sixty boys with a confirmed diagnosis of PUV as neonates (gestational age [GA]<44 weeks) throughout 2001-2016 were included. Clinical data were collected from medical records. Renal function was assessed by nadir plasma creatinine, creatinine at the last follow-up, and glomerular filtration rate (GFR) at the last follow-up. The GFR was estimated using the Schwartz formula. Renal function was classified according to the kidney disease: improving global outcomes (KDIGO) guidelines' grades of chronic kidney disease (CKD). Glomerular filtration rate > 90 ml/min/1.73m2 at the last follow-up was classified as normal renal function. RESULTS: Twelve patients (20%) had ascites and/or urinoma, and 48 (80%) did not. GA and birth weight were not different in patients with and without extravasation. PUV was suspected from prenatal ultrasound findings in 66.7% of the patients in both groups. Median nadir creatinine was 21 (range, 11-33) µmol/L in boys with ascites/urinoma, and all values were within the age-adjusted reference values. Nadir creatinine was 23 (14-199) µmol/L in boys without extravasation, and it was above the normal range in 14 boys. The incidence of elevated nadir creatinine was significantly different in the two groups (p < 0.025). One of the 12 patients with extravasation developed chronic renal failure (CKD 3). In the group of 48 patients without extravasation, 20 (42%) had chronic renal failure grade 2-5, and among these, 5 patients have had a renal transplant (CKD grade 5). The prevalence of CKD grade 2-5 was statistically different in the two groups (p = 0.03). These findings are presented in the summary figure. CONCLUSION: Extravasation of urine was found in 12 of 60 (20%) boys with PUV. These patients had significantly lower prevalence of CKD at the last follow-up than patients without extravasation. This finding is important in prenatal counseling. It also indicates that prenatal decompression of the bladder and upper tract is beneficial in patients with PUV, which is relevant to the discussion of prenatal intervention in these fetuses.

[Consequences of prostatic obstruction on bladder function, impact of removal, and management of recurrence after surgery]. / Conséquences de l'obstruction prostatique sur le fonctionnement vésical, impact de la désobstruction, et prise en charge des récidives après chirurgie.

OBJECTIVE: Our objective was to evaluate bladder outlet obstruction (BOO) consequences on the detrusor activity, to analyze the impact of medical and surgical treatments, and to study the reasons for recurrence of urinary symptoms after surgical treatment. METHOD: A non-systematic review of the scientific literature was conducted from the PubMed database to retrieve the most relevant scientific publications between 2000 and July 2018 with the keywords: BPH, bladder obstruction, bladder instability, surgery, and reoperation. A first research was crossed with the results of the reviews of literature already published and was enriched by the contributions of the various authors. A synthesis has been proposed. RESULTS: The consequences of bladder outlet obstruction (BOO) on the detrusor may be detrusor overactivity (DOA) or detrusor hypocontractility. DOA is found in about 50% of patients at the time of their surgery and its evolution is most often favorable after surgical treatment (resolved or reduced in 2/3 of cases). Bladder hypocontractility is responsible for acute or chronic urinary retention. It can be the cause for poor postoperative micturition recovery requiring self-catheterization which the patient must have been informed before surgical treatment. Surgery reduces urinary symptoms with a low but significant surgical revision rate (10 to 30% depending on the surgical technique). The less efficient technique with regard to surgical revision rates are prostatic radiofrequency or cervico-prostatic incision, followed by laser vaporization techniques, TURP and adenomectomy (surgical or endoscopic). Adenomectomy is the surgical technique that has the lowest recurrence rate. The identified risk factors for surgical revision are the surgeon's experience, the power of the laser (in case of photovaporization), the surgical technique employed, the length of operative time, the low or excessive volume of the prostate, the significant pre-operative post-void residual volume, and the slight decrease of postoperative PSA level. Prior to any surgical revision for recurrence of urinary symptoms, the assessment should include the review of previous surgical report, the evaluation of the resected prostatic volume and the residual prostatic volume, the IPSS score, the calendar of micturition, the urethrocystoscopy and the urodynamic assessment. CONCLUSION: BOO can lead to bladder dysfunction such as DOA or detrusor hypocontractility. Resolution of BOO by a suitable surgical treatment allows, in the majority of the cases, to resolve bladder dysfunctioning. In case of failure, the assessment must be complete to define the causes and to find the most suitable solution.

Long-term renal outcome in infants with congenital lower urinary tract obstruction.

INTRODUCTION: Congenital Lower Urinary Tract Obstructions (LUTO) is a heterogeneous group of diseases in which urine elimination is obstructed at the level of bladder neck or urethra. The aim of the study is to evaluate the long-term renal outcome of patients suffering of congenital LUTO. PATIENTS AND METHOD: We retrospectively reviewed patients with congenital LUTO. All patients had at least 1 year follow-up. Data on surgery, renal imaging and Schwartz estimate creatinine clearance were collected. Incidence of Chronic Renal Disease (CRD) is presented with Kaplan-Meier method. RESULTS: 40 patients were included, 23 patients with Posterior Urethral Valve (PUVs) and 17 patients with other aetiologies: anterior urethral valve (2), urethral atresia (2), urethral stenosis (2), cloacal malformations (2), obstructive ureterocele (1), bladder trigone malformation (1) and neonatal bladder-sphincter dysfunction without neurological abnormalities (7). Incidence of CRD at age 10 years was 37% in congenital LUTO, 42% in PUVs and 30% in other aetiologies, and was significantly higher in PUVs (P=0.032). Renal prognosis was significantly worsened by discover of retentional bladder wall changes in initial cystoscopy, and by loss of parenchymal differentiation or cortical microcysts in first ultrasonography. The use of urinary diversion was significantly higher in LUTO of other aetiologies. CONCLUSION: A high incidence of CRD is observed in patients with congenital LUTO, significantly higher in patients with PUV. LUTO of other aetiologies require step by step surgical management and higher use of urinary diversion. Precise initial evaluation in cystoscopy and ultrasonography is required and participate to evaluate future renal outcome. LEVEL OF INCIDENCE: 4.

Current strategies to predict and manage sequelae of posterior urethral valves in children.

Posterior urethral valves (PUV) constitute a significant urological cause of chronic kidney disease (CKD) in children. The condition is characterised by the unique pathophysiology of the evolution of bladder dysfunction after relief of obstruction, which contributes to CKD. Improvements in prenatal diagnosis followed by selective foetal intervention have not yet produced improvement in long-term renal outcomes, although better patient selection may alter this in the future. Proactive management with surveillance, pharmacotherapy, timed voiding, double voiding, and/or assisted bladder-emptying, is being increasingly offered to those with severe bladder dysfunction and has the potential of reducing the burden of renal disease. Clinicians are currently able to counsel regarding the prognosis using serum creatinine and other emerging markers. However, much of this work remains to be validated. Satisfactory graft survival rates are now reported with aggressive management of bladder dysfunction in children who are candidates for renal transplantation. Knowledge gaps exist in identifying early markers of renal injury, risk stratification, and in understanding patient and carer perspectives in PUV.

Are nomograms based on free uroflows helpful to evaluate urethral obstruction in men?

AIMS: It was demonstrated earlier that reduced maximum flow-rate (Qmax ) during intubated flow (IF) in women may be the consequence of a urethral reflex. Over-estimation of outflow obstruction is the consequence. Our hypothesis, that a similar phenomenon could occur in men, is tested using results of a free uroflow (FF) preceding an IF to eventually correct the Abrams-Griffiths (AG) number. METHODS: Retrospectively, analysis of 441 urodynamic studies of men suspected of bladder outflow obstruction (BOO) was performed. The Valentini-Besson-Nelson model links outflow obstruction (parameter pucp) and the detrusor contractility (parameter k) to Qmax and detrusor pressure at Qmax (pdet.Qmax ). AG and pucp are strongly correlated. Contractility is described by a graphical representation (a nomogram) which numerical fitting is an algebraic equation f(Qmax ,pdet.Qmax ). Nomograms based on IF allowed computing a calculated AG (corr-AG) on the basis of free flow. RESULTS: Included files (N = 362) had filling volume during FF > 90 mL; corr-AG was compared to AG. When Qmax.FF > 1.5*Qmax.IF (N = 114), 61 patients (53.5%) were found less obstructed with corr-AG, no one more obstructed. Increased BOO could be the result of a urethral reflex during IF and AG gave an overestimation. When Qmax.FF < 1.5*Qmax.IF (N = 248), only 39 patients (12.1%) were found less obstructed with corr-AG and 28 (11.3%) more obstructed. CONCLUSION: To obtain a reliable evaluation of BOO in men, it is suitable to perform a FF before IF. A corrected AG (corr-AG) obtained from IF analysis and nomograms based on FF may be helpful for evaluation of BOO in men.

VBN-based nomograms provide critical voiding parameters which can be used for invasive or non-invasive flow interpretation of women at risk of obstruction over time.

AIMS: To design a simple office-based method to evaluate characteristic parameters from free uroflowmetries (FF) or pressure flow studies (PFs). This method can be applied by any physician to any recording, for instance in the follow-up of women at risk of developing outflow obstruction over time after surgical interventions. METHOD: Using pressure-flow studies (PFs), a reliable evaluation of urethral obstruction (U) and detrusor contractility (k) parameters could be obtained from the maximum flow rate and detrusor pressure at maximum flow rate. Nomograms for these parameters were derived from theoretical computations using the VBN model. Then, to allow an evaluation of the real urethral obstruction, a protocol was designed incorporating FF data in the follow-up of women suspected of urethral obstruction. RESULTS: Two nomograms were obtained: (1) A urethral obstruction nomogram allowing to define a Woman Obstruction Index (WOI = pdet.Qmax - 0.5*Qmax ) which has the same structure than the A-G number in men. (2) A detrusor contractility nomogram which was generalized to all initial bladder volumes. The curves were fitted by algebraic equations easily programmable on any handheld device. CONCLUSION: Using a mathematical model of micturition and data extracted from PFs, two nomograms on urethral obstruction and detrusor contractility were designed. This tool offers a rapid and practical method for the clinician to follow women at risk of obstruction over time. Its applications will be the purpose of further studies. Neurourol. Urodynam. 36:37-42, 2017. © 2015 Wiley Periodicals, Inc.

Long-term Impacts of Concurrent Posterior Urethral Valve Ablation and Bladder Neck Incision on Urinary Continence and Ejaculation.

OBJECTIVE: To assess the long-term impacts of bladder neck incision (BNI) on continence and ejaculatory function of adults who underwent concurrent posterior urethral valve (PUV) ablation and BNI during childhood. MATERIALS AND METHODS: A retrospective chart review was performed to find all adult patients with relevant history. All patients had undergone BNI at 6 o'clock proximal to the verumontanum with caution to leave the adventitia and verumontanum untouched. Charts were reviewed and attempts were made to contact those ≥18 years old for follow-up. Patients were specifically evaluated for lower urinary tract symptoms and ejaculatory condition. RESULTS: Among patients treated for PUV between 1998 and 2015 in our center, 21 were ≥18 years old at the time of assessment. Until February 2016, we were able to contact 18 patients, all of whom agreed to participate. Mean age was 21.1 ± 2.9 years with a mean follow-up of 12.5 ± 4.8 years. None of those contacted had incontinence or dry ejaculations. All considered their ejaculations normal and only one complained of weak ejaculations. Four of 5 patients who consented to perform a semen analysis had normal tests and 1 had low sperm count with abnormal motility. CONCLUSION: BNI is not associated with additional risk of incontinence and dry ejaculation in early adulthood and preserves antegrade ejaculation. Concomitant valve ablation with BNI may provide additional benefits in care of PUV children, especially those with prominent bladder neck and poor bladder function at presentation.

Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome.

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized.

Effect of Doxazosin on Autonomic Nervous Control and Urodynamics of Rat Urinary Bladder during Modeled Infravesical Obstruction.

The therapeutic effect of doxazosin (40 µg/kg/day over one month) on urinary bladder was examined in female rats with modeled chronic infravesical obstruction (IVO) produced by graduated mechanical constriction of the proximal urethral segment. In one month, IVO induced a pronounced vesical hypertrophy both in treated and untreated rats that manifested in increased bladder weight and capacity, the latter increment being pronouncedly greater in treated rats. In untreated IVO rats, infusion cystometry revealed elevated basal intravesical pressure of void bladder P0, markedly increased maximal (premicturitional) pressure Pmax, and increased amplitude of spontaneous oscillations of intravesical pressure ΔPdet in filled bladder. Doxazosin produced no significant effect on Pmax rise during IVO, but prevented elevation of P0 and increment of ΔPdet in filled bladder. During gradual filling of urinary bladder in control (intact) rats, the parasympathetic vesical influences increased progressively, while in untreated IVO rats, the adrenergic influences prevailed even at maximal filling of the bladder. In IVO rats, doxazosin prevented the bias of the sympathetic-parasympathetic balance in the filled bladder in favor of sympathetic influences, but did not prevent this bias in a void bladder. It is hypothesized that α-adrenoblockers improve micturition during IVO caused by benign prostatic hyperplasia not only by decreasing the urethral resistance to urine flow due to down-regulation of prostate smooth muscle tone, but also by a direct action of these blockers on detrusor adrenergic receptors and central structures involved in urinary bladder control.

Treatment and re-characterization of mouse obstructive genitourinary syndrome.

We aimed to characterize and to explore a treatment for a condition in which male mice exhibited a solid bulge in the preputial area and an inability to breed. Twenty-seven mice from several animal housing institutions in Spain were included in this study for microbiological and pathological characterization of this condition. The condition mostly affected breeding animals and was associated with the C57BL/6J genetic background. A solid, yellowish-white substance was found inside the prepuce, which displaced the penis cranially, preventing its externalization and limiting the animal's capacity to breed. This pattern was almost identical to that of post-coital vaginal plugs, suggesting that the blocking substance originated from ejaculate. Opposite to what was suggested in previous publications, the penis was completely intact in all of the cases, with no signs of mutilation or wounds. Based on our findings, we developed a surgical technique to clear the prepuce and recover breeding performance, which we tested in 15 other mice with the condition. We eliminated the blocking substance and recurrence of the condition by surgically opening the prepuce, and most of the animals recovered fertility.

Effect of Selective Prostaglandin E2 EP2 Receptor Agonist CP-533,536 on Voiding Efficiency in Rats with Midodrine-Induced Functional Urethral Obstruction.

OBJECTIVES: We investigated the effect of the selective prostaglandin E2 EP2 receptor agonist CP-533,536 on voiding efficiency in rats with midodrine-induced functional urethral obstruction. METHODS: The effect of CP-533,536 (0.03-0.3 mg/kg, intravenous [i.v.]) on urethral perfusion pressure (UPP) was investigated in anesthetized rats pre-treated with midodrine (1 mg/kg, i.v.), which forms an active metabolite that acts as an α1 -adrenoceptor agonist. The effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on cystometric parameters was also investigated in anesthetized rats. In addition, the effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on residual urine volume (RV) and voiding efficiency (VE) was investigated in conscious rats treated with midodrine (1 mg/kg, i.v.). RESULTS: CP-533,536 dose-dependently decreased UPP elevated by midodrine in anesthetized rats. In contrast, CP-533,536 did not affect maximum voiding pressure, intercontraction interval, or intravesical threshold pressure. In conscious rats, midodrine (1 mg/kg, i.v.) markedly increased RV and reduced VE. CP-533,536 dose-dependently ameliorated increases in RV and decreases in VE induced by midodrine. CONCLUSIONS: These results suggest that a selective EP2 receptor agonist could ameliorate the elevation of RV and improve the reduction of VE in rats with functional urethral obstruction caused by stimulation of α1 -adrenoceptors. The mechanism of action might be not potentiation of bladder contraction but rather preferential relief of urethral constriction.

Comparative Influence of Imidafenacin and Oxybutynin on Voiding Function in Rats with Functional Urethral Obstruction.

An antimuscarinic therapy may increase the risk of voiding dysfunction. However, it is unclear whether the relative risk of voiding dysfunction is different among antimuscarinics. Therefore we determined the potencies both in enhancing the bladder capacity (BC), effectiveness, and in decreasing the maximum urinary flow rate (Qmax), voiding dysfunction, to compare their therapeutic indices.Under urethane anesthesia, urinary flow rate was measured at distal urethra using an ultrasonic flow meter in female Sprague-Dawley rats with functional urethral obstruction induced by a continuous i. v. infusion of α1-adrenoceptor agonist A-61603 (0.03 µg/kg/min). In a separate group of urethane-anesthetized rats without urethral obstruction, an intermittent cystometry was performed to determine BC.Intravenous imidafenacin and oxybutynin produced a significant dose-dependent decrease in Qmax with the minimum doses of 0.03 and 1 mg/kg, respectively. Imidafenacin and oxybutynin markedly increased BC, with minimum doses of 0.01 and 3 mg/kg, respectively. At the minimum dose to increase BC, oxybutynin caused a significant increase in residual urine volume with a significant decrease in voiding efficiency, whereas imidafenacin had no influence on these values. The relative influence index, which is the ratio of the minimum influence dose between in decreasing of Qmax and in increasing of BC, of imidafenacin was 10 fold higher than that of oxybutynin.This study suggests that imidafenacin has a lower relative risk of voiding difficulty compared with oxybutynin in rats. These results provide new information that antimuscarinics may have varying degrees of impact on voiding difficulty.