Abstracts
2000 Digestive Disease Week

# 2321 Stasis Is Associated with Ileal J-Pouch Inflammation and Oxidative Stress in a Rat Model of Ileal Pouch-Anal Anastomosis (IPAA).
Khaled O Shebani, Arthur F. Stucchi, James P. McClung, Eve R. Beer, Wayne W. Lamorte, James M. Becker, Boston, MA

Introduction: Colectomy with IPAA is the operation of choice for patients with chronic ulcerative colitis, but pouchitis remains a major late complication. Fecal stasis has been implicated in the etiology of pouchitis; however, the mechanism is unclear, in part, due to the lack of a reproducible animal model. Our goal was to surgically mimic the IPAA procedure in a rat to investigate the hypothesis that stasis leads to biochemical changes that predispose the ileal pouch to inflammation. Methods: 22 Sprague-Dawley rats underwent total colectomy with either straight (st)ileorectal or ileal J pouch-rectal anastomosis and 6 non-operated (non-op) controls. 30 days post-op, animals were randomized into 2 groups: no dextran sulfate sodium (DSS) or 5% DSS in the water for 4 days. Urinary 8-isoprostane (8-IP)levels were measured as a marker of oxidative stress and mucosal neutrophil infiltration was assessed by histology and myeloperoxidase activity (MPO). Results: Survival was = 95% and weight gain after 12 days matched controls. Serial barium radiographs over 48 hr showed stasis in the J-pouches, and charcoal transit time was 3x longer (pŁ0.05)than that in straight ileorectal rats. MPO was significantly elevated in J-pouch rats and this was exacerbated by DSS which produced increased 8-IP levels (pŁ 0.05),pouch ulcerations, diarrhea and rectal bleeding (Table). Conclusions: 1) Construction of an ileal J-pouch following colectomy is technically feasible in a rat; 2) Stasis in the J-pouch is associated with elevations in MPO and 8-IP, providing evidence of neutrophil infiltration and oxidative stress; 3) DSS augments stasis-induced ulceration and produces pathological findings similar to pouchitis suggesting this may be a viable model to study the pathogenesis of pouchitis.