Abstracts
2000 Digestive Disease Week

# 2230 Matrix Metalloproteinase Inhibition Enhances Colonic Anastomotic Healing.
Teruo Kiyama, M. Onda, A. Tokunaga, David T. Efron, Adrian Barbul, Baltimore, MD, Tokyo, Japan

Wound strength is a balance between collagen synthesis and degradation. During anastomotic healing, marked collagenolysis occurs early and affects the integrity and strength of the anastomosis. We therefore investigated the role of collagenase (matrix metalloproteinases[MMPs]) inhibition in colonic healing by using BE16627B, a new MMP inhibitor. Twentyone male Sprague-Dawley rats (270-290g) underwent identical surgical manipulation consisting of colon anastomosis (single layer, inverted)and dorsal subcutaneous implantation of osmotic pumps. Animals were randomly assigned to received either BE16627B, which was dissolved in a vehicle solution of DMSO and ethylene glycol (equal volumes) at a concentration of 10mg/100ml, or vehicle solution alone. Animals were sacrificed 4 days after surgery and anastomotic bursting pressure was assessed (CBP). As an index of new and mature collagen, the hydroxyproline contents of the soluble and insoluble fractions of anastomotic collagen was measured in tissue hydrolysates. a-amino nitrogen content of the hydrolysate was determined as a measure of total tissue protein content. Histologic examination revealed less early re-epithelialization and less granulation at the anastomotic site of BE16627B-treated animals. The data demonstrates that inhibition of MMP activity during acute anastomotic healing enhances both wound strength and the soluble fraction of anastomotic collagen. These results suggest that MMP activity affects soluble collagen accumulation in the healing anastomosis.