Abstracts
2001 Digestive Disease Week

# 1766 Mycophenolate Mofetil Impairs Healing of Left Sided Colon Anastomosis and Insulin-Like Growth Factor-I Tends to Neutralize this Impairment
Gregor Baumann, Roman Inglin, Dorothee Schoenfeld, Olaf Dirsch, Joerg Zeeh, Markus W Buechler, Bernhard Egger, Bern, Switzerland, Essen Germany

Introduction: Inadequate healing and consequent leakage from bowel anastomosis are a significant cause of postoperative morbidity and mortality. Immunosuppressive drugs are known to disturb healing processes and to impair the mechanical stability of bowel anastomosis. Recently we were able to demonstrate that Mycophenolate mofetil (MMF), an immunosuppressive agent that selectively inhibits the proliferation of T and B lymphocytes and has been shown to be effective in inflammatory bowel disease and in preventing allograft rejection after organ transplantation, impairs significantly anastomotic healing in rats. Previously we were able to show that Insulin-like growth factor-I (IGF-I) promotes and accelerates healing of bowel anastomosis in rats. The aim of the present study was to evaluate whether systemic IGF-I treatment might neutralize the observed negative effect of MMF on healing of colonic anastomosis in rats.
Methods: Rats underwent laparotomy, division of the left colon and sigmoido-sigmoidostomy. MMF (25mg/kg) and the vehicle of IGF-I or MMF and IGF-I (1mg/kg) or both vehicles were administered intraperitoneally in three groups (n=21 per group) 3 days prior to surgery (MMF) or the day before surgery (IGF-I), and then once daily until sacrifice (7 animals per group; 2,4 and 6 days after surgery). Bursting pressure measurements of the anastomotic sites were performed.

Results: Administration of MMF significantly decreased anastomotic bursting pressure on the second and fourth postoperative day, as previously demonstrated. In animals treated with MMF and IGF-I levels of anastomotic bursting pressures measurements were similar to the ones observed in control (vehicle) animals. However, this increase did not reach statistical significance (P=0,06 and 0,09) due to a wide range of the bursting pressure data in both groups.

Conclusion: Administration of the immunosuppressive agent MMF again impairs healing and mechanical stability of colon anastomosis in rats during the early postoperative period, which confirms our previous findings. The growth factor IGF-I tends to neutralize this negative MMF-effect on anastomotic healing with findings of a very similar stability of anastomoses as observed in control (vehicle) animals. These preliminary findings may provide insight into new therapeutic approaches to ensure anastomotic healing in immunocompromised hosts as patient after transplantation or IBD patients on an immunosuppressive regimen.