In vitro evaluation of ureteral contractility: a comparative assessment of human, porcine and sheep ureteral response to vardenafil.

OBJECTIVES: Basic science studies of ureteral physiology and pathophysiology are commonly performed on animal ureters due to several limitations associated with human ureteral sampling. In this work we question whether animal ureters are good replicas of human ureteral behavior for pharmacological studies. MATERIALS AND METHODS: Ureteral rings from human, porcine and ovine ureters underwent the same organ bath protocol. After stimulation with KCl, ureters were subjected to different doses of vardenafil. Basic contractility and ureteral response to vardenafil were analyzed. RESULTS: A different pattern of basic contractility was evidenced between species. Vardenafil administration induced a dose-dependent reduction in KCl-induced amplitude increase in human ureters and a dose-dependent reduction in autonomic contractile rhythm of porcine and ovine ureters. Although animal ureters could predict the relaxant response of human samples to vardenafil, its effect would have been overestimated using only animal models. CONCLUSIONS: Human ureteral investigations cannot entirely be replaced by existing animal models since results of the latter will vary significantly according to the tested pharmaceutical agent.

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial.

BACKGROUND: Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications.Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation.This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. METHODS/DESIGN: The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo.Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a reduction in the incremental cost per quality-adjusted life years, determined at 12 weeks. The analysis will be based on all participants as randomized (intention to treat). The trial has 90% power with a type I error rate of 5% to detect a 10% increase in primary outcome between the tamsulosin and nifedipine treatment groups. TRIAL REGISTRATION: ISRCTN69423238; EudraCT number: 2010-019469-26.

[The information value of rheography and loading tests in the functional assessment of the ureter (experimental research)]. / Informativnost' reografii i nagruzochnykh testov v otsenke funktsii mochetochnika (éksperimental'noe issledovanie).

Functional tests, using electro-ureterography, ureteral rheography, electromanometry and electromagnetic flowmetry in the presence of diuretic and perfusion load tests, were performed at surgery in dogs. Ureteral rheography is shown to be a valuable method for the assessment of ureteral motility (as evidenced by ureteral volume changes), and have certain advantages over other techniques so that it can be used clinically for preoperative functional assessment of ectatic ureters. Load tests are necessary at functional tests of the upper urinary system in order to assess the pattern of ureteral wall contractility and reserves.