title: A novel ex-vivo ureteral apparatus for assessing the impact of intraluminal pharmaceutical agents on ureteral physiology.
abstract: OBJECTIVE
  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.
  
  
  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 μM) 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 μM, while intraluminal nifedipine needed 10.2 ± 1.1 μM. 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.
authors: Department of Urology, University of California at Irvine, Irvine, California, USA. donaldp@pacmed.org
authors: Donald L
authors: DL
authors: Pick
authors: Stanislav
authors: S
authors: Shelkovnikov
authors: Adam G
authors: AG
authors: Kaplan
authors: Michael K
authors: MK
authors: Louie
authors: Ralph
authors: R
authors: Purdy
authors: Elspeth M
authors: EM
authors: McDougall
authors: Ralph V
authors: RV
authors: Clayman
mesh_terms: D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology*; D010528:Peristalsis / Q000187:drug effects; D011312:Pressure; D012212:Rheology / Q000187:drug effects; D034421:Sus scrofa; D014513:Ureter / Q000187:drug effects* / Q000502:physiology*
chemical_list: D009543:Nifedipine