Pouchitis in a rat model of ileal J pouch-anal anastomosis.
Endorectal ileal pouch-anal anastomosis (IPAA) has become the operation of choice for patients with chronic ulcerative colitis. Although this procedure improves the quality of life, pouchitis remains a significant postoperative complication. Because our understanding of the pathophysiology of pouchitis may, in part, be due to the lack of small animal model, our aim was to develop a model of IPAA in a rat that mimics its clinical counterpart. Colectomy, proctectomy, construction of an ileal J pouch, and ileal pouch-rectal anastomosis as a model of IPAA was performed in Sprague-Dawley and Lewis rats. Radiographic contrast studies were performed to quantitate intestinal transit. The presence of activated neutrophils was quantified by measuring mucosal myeloperoxidase (MPO) activity. Oxidative stress was quantitated by measuring urinary 8-isoprostane (8-IP) levels. Anaerobic and aerobic bacterial counts were determined on Brucella and tryptic soy agar plates, respectively. Dextran sulfate sodium (DSS) was used to exacerbate ileal J pouch inflammation. Mortality was low, and animals gained weight normally after recovery. Stasis was documented radiographically. MPO levels were elevated (p < 0.05) in the ileal J pouch 30 and 60 days after IPAA, indicating an inflammation that was associated with stasis and bacterial overgrowth. 8-IP levels were elevated by 80% compared with controls. Oral administration of 5% DSS to IPAA rats with further elevated MPO and 8-IP levels in concert with a pouchitis-like syndrome that included the physical, gross, and histologic characteristics of clinical pouchitis. An understanding of the pathophysiology of pouchitis is essential to the future development of new therapeutic modalities. This model is applicable to investigating several key etiologic mechanisms purportedly related to pouchitis.
Shebani
Khaled O
KO
Department of Surgery, Boston University School of Medicine, Massachusetts 02118, USA.
Stucchi
Arthur F
AF
Fruin
Brent
B
McClung
James P
JP
Gee
Denise
D
Beer
Eve R
ER
LaMorte
Wayne W
WW
Becker
James M
JM
D001003:Anal Canal / Q000503:physiopathology / Q000601:surgery*; D000714:Anastomosis, Surgical / Q000009:adverse effects*; D000818:Animals; D003082:Colectomy / Q000009:adverse effects; D003093:Colitis, Ulcerative / Q000503:physiopathology / Q000601:surgery*; D004195:Disease Models, Animal; D005772:Gastrointestinal Transit / Q000502:physiology; D007082:Ileum / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D011183:Postoperative Complications; D019449:Pouchitis / Q000209:etiology* / Q000503:physiopathology*; D016737:Proctocolectomy, Restorative / Q000009:adverse effects*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley