A novel ex-vivo ureteral apparatus for assessing the impact of intraluminal pharmaceutical agents on ureteral physiology.

摘要

BACKGROUND AND PURPOSE: Safe intraluminal access to the ureter and kidney is essential for endourologic procedures. Pharmacologic manipulation of ureteral smooth muscle could conceivably ease access and decrease morbidity. To minimize systemic effects, local intraluminal administration would be optimal, but the urothelium presents a barrier to the passage of medications. We present a novel ex-vivo apparatus and technique to measure ureteral peristalsis and assess drug diffusion. MATERIALS AND METHODS: Excised 3-cm pieces of porcine or human ureters were placed inside a specially designed apparatus that allows separate manipulation of the intra- and extraluminal environments while measuring peristalsis. Intraluminal antegrade perfusion was maintained by a reservoir. A pressure transducer was placed at the inflow end of each ureter segment. After equilibration, phenylephrine (10 muM) was then added extraluminally to induce peristalsis. Nifedipine was then added to the intraluminal reservoir or the external organ bath. The concentration of nifedipine needed to cause aperistalsis was measured. RESULTS: In 12 trials, extraluminal nifedipine caused aperistalsis at a concentration of 1 +/- 0.1 muM, while intraluminal nifedipine needed 10.2 +/- 1.1 muM. Significantly higher concentrations of nifedipine were needed intraluminally to cause aperistalsis, (P < 0.0001). CONCLUSIONS: With our apparatus, we can control the intraluminal and extraluminal ureteral environments, and measure peristalsis before and after drug administration. This apparatus should help investigators who are interested in studying both the diffusion of a wide range of drugs, as well as the effects of those medications on ureteral physiology. In this study, the urothelium acted as a significant barrier to the diffusion of nifedipine.