First prize: Chitosan and the urothelial barrier: effects on ureteral intraluminal drug penetration and peristalsis.
BACKGROUND
Relaxing the ureter prior to endourologic procedures could ease instrument access. In an ex-vivo model, intraluminal nifedipine has been shown to relax the ureter. Chitosan is the deacetylation product of chitin and can alter bladder urothelium. This study examines the effect of nifedipine on peristalsis before and after pretreating the ureter with chitosan.


METHODS
Intact 4-cm tubular porcine ureteral segments were placed in a novel organ bath. To induce peristalsis, phenylephrine (10 μM) was added. Chitosan (0.5% [w/v], 30 minutes) or Krebs (control) was then used to treat the urothelium. The rate and amplitude of ureteral peristalsis was then measured. Intraluminal nifedipine (1 μM) was then added to the intraluminal reservoir. Peristaltic rate and amplitude and the time to aperistalsis were measured. Methylene blue was then added after treatment with chitosan or control to measure diffusion.


RESULTS
After Krebs pretreatment, intraluminal nifedipine (1 μM) significantly reduced peristaltic frequency (p = 0.0184) but did not stop peristalsis after 60 minutes of exposure in six trials. After chitosan, nifedipine (1 μM) stopped ureteral peristalsis within an average of 12.30 ± 4.72 minutes. Chitosan alone did not cause aperistalsis. Intraluminal methylene blue did not diffuse into the extraluminal bath after saline or chitosan pretreatment. Histological analysis of the ureter before and after pretreatment with chitosan showed no urothelial disruption.


CONCLUSIONS
By pretreating the intraluminal surface of the ureter with chitosan, nifedipine blocks ureteral peristalsis at low concentrations. Chitosan changes ureteral urothelial permeability without barrier disruption and has no observed effect on ureteral contraction.
Department of Urology, University of California at Irvine, Irvine, California, USA. donaldp@pacmed.org
Donald L
DL
Pick
Stanislav
S
Shelkovnikov
Noah
N
Canvasser
Michael K
MK
Louie
Jane
J
Tongson-Ignacio
Elspeth M
EM
McDougall
Ralph V
RV
Clayman
D000818:Animals; D001363:Awards and Prizes; D048271:Chitosan / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D010528:Peristalsis / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D013194:Staining and Labeling; D034421:Sus scrofa; D014513:Ureter / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019459:Urothelium / Q000187:drug effects*
D010656:Phenylephrine; D048271:Chitosan; D009543:Nifedipine