Mycophenolate mofetil impairs healing of left-sided colon anastomoses

Introduction. Inadequate healing and consequent leakage from bowel anastomo ses are a significant cause of postoperative morbidity and mortality. Immun osuppressive drugs are known to disturb healing processes and to impair the mechanical stability of bowel anastomosis. Mycophenolate mofetil (MMF) is an immunosuppressive agent that selectively inhibits the proliferation of T and B lymphocytes and has been shown to be effective in preventing allogra ft rejection after organ transplantation. Adverse effects are few; however, nothing is known in regard to possible adverse effects of MMF administrati on on the healing of bowel anastomosis. The aim of the present study was to evaluate the effect of systemic MMF administration on the healing of colon anastomoses in rats. Methods. Rats underwent laparotomy, division of the left colon, and sigmoid ostomy, MMF (25 mg/kg) or vehicle was administered intraperitoneally in two groups (n=21 per group) 3 days before surgery and then once daily until eu thanization (7 animals per group; 2, 4, and 6 days after surgery). Bursting pressure measurements, histologic evaluation, morphometric analysis, mucin and collagen staining, and BrdU immunohistochemistry of the anastomotic si te were performed. Furthermore, matrix protein expression at the anastomoti c site was determined by collagen I and fibronectin Western blots. Results. Administration of MMF significantly decreased anastomotic bursting pressure postoperatively, Accordingly, histology, mucin staining, and BrdU immunohistochemistry and measurements of the colonic crypt depth showed mo re extended inflammation, a significantly lower proliferation rate, and a s ignificantly thinned mucosal layer in the MMF-treated groups when compared to control animals, whereas matrix synthesis at the anastomotic site was no t different. Conclusions. The administration of the immunosuppressive agent MMF signific antly impairs healing and mechanical stability of colon anastomosis in rats during the early postoperative period. MMF act to disturb host reparative processes mainly by impairment of reparative colonic epithelium proliferati on and less by a disturbance of matrix synthesis.