Pouchitis in a Rat Model of Ileal J Pouch–Anal Anastomosis

Abstract

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.

Partially Hydrolyzed Guar Gum Attenuates the Severity of Pouchitis in a Rat Model of Ileal J Pouch-Anal Anastomosis

“…Although rodent models have been used to study several aspects of pouchitis, these models lacked many of the clinical signs of pouchitis such as diarrhea and rectal bleeding, and thus they had no real clinical relevance. Shebani et al [25] developed a feasible rat model of IPAA. They showed that the ileal J pouch becomes significantly inflamed after 30 days and DSS can be successfully used to reproducibly exacerbate ileal pouch inflammation and produce accompanying diarrhea, mucosal ulcerations, and rectal bleeding, similar to clinical pouchitis.…”

“…In Shebani's study, the only physical sign of pouchitis in rats was loose stools [25]. Other signs frequently associated with pouchitis were missing.…”

“…2). The surgical technique has been described in detail elsewhere [25]. The anastomosis was tested for leakage by injecting warm normal saline into the anal canal through a fine catheter.…”

“…Four micrometer sections were taken on slides and stained with hematoxylin and eosin. Microscopic examination: intestinal specimens were evaluated according to the criteria described by Shebani et al [25]. Erosion was evaluated as 0 (negative), 1 (focal erosion+), 2 (erosion is observed in many regions), or 3 (extensive erosion).…”

Surgical Prophylaxis of Pouchitis in Ulcerative Colitis

“…Both of these mechanisms can compromise epithelial integrity and barrier function, thus predisposing the ileal pouch mucosa to a low-grade inflammatory response. Both anaerobic and aerobic bacteria overgrow the ileal pouch at 30 days postoperatively [33,34].…”