The influence of fibrin sealant on the healing colonic anastomosis : an experimental study in rats

The experiments described in this thesis were performed in order to find methods to influence and improve colonic anastomotic wound healing. It is known that inflammation may affect the healing of colonic anastomoses. Eicosanoids are known mediators of the inflammatory process, being a part of the healing process. In order to influence the healing process anti inflammatory drugs may be used. To evaluate the possible role of eicosanoids in uncomplicated healing of colon anastomosis we decided to measure eicosanoid synthesis in colon tissue and peritoneal macrophages. Activity of peritoneal macrophages was studied based on the HPLC profile of eicosanoids. Colon tissue was studied as well in order to compare both profiles to establish which cell type is active in the healing colon (Chapter IV). Colonic anastomoses may be covered with fibrin sealant in order to promote wound healing and prevent leakage. Presently, this is already performed in many clinical situations. However data from experimental animal studies are conflicting, and prospective clinical studies are lacking. The influence of human· and rat fibrin sealant on the mechanical strength en collagen metabolism of a sutured colonic anastomoses is investigated (Chapter V). Ischemia of the wound margins is a high-risk condition in the healing colonic anastomosis, with a considerable chance of anastomotic dehiscence. The effect of fibrin sealant on the healing ischemic anastomosis is tested (Chapter VI). Another known risk-factor is the presence of peritonitis. The role of fibrin sealant in the presence of faecal peritonitis is described in Chapter VII. A technical imperfect anastomosis may result in leakage of intestinal contents. In order to examen the effect of fibrin sealant in such a complication, fibrin was applied in a model of "incomplete anastomosis", constructed with 4 sutures only (Chapter VI!!). Due to the high bacterial load of the colon, bacterial contamination of an anastomosis as well as the applied fibrin sealant is a possible negative factor in wound healing. Bacterial contamination is a known stimulus for inflammatory reaction. Fibrin sealant can be used as a vehicle for local application of antibiotics to the anastomosis. In the last experiment the effect of antibiotics in fibrin sealant on healing anastomoses in the rat was tested (Chapter IX).