Reduction of adhesion formation by intraperitoneal administration of a recombinant Hirudin analog.

Abstract

Adhesion formation is a major source of postoperative morbidity and mortality. Therefore, the reduction of postoperative adhesion formation would be of clinical benefit. Various modalities have been shown to reduce adhesion formation, including fibrinolytic enzymes, nonsteroidal anti-inflammatory drugs, and barriers that reduce the apposition of sites of potential adhesion formation. This study examined the ability of an inhibitor of thrombin, a recombinant hirudin analog (recHirudin), to reduce the formation of intraperitoneal adhesions in two rabbit models of adhesion formation. In the sidewall and double uterine horn models, recHirudin was administered via Alzet miniosmotic pump for the entire postoperative interval. In both of these models, there was a dose-dependent reduction in adhesion formation as measured by (1) the area of the sidewall injury that was involved in adhesions to the cecum and the bowel or (2) the involvement of the uterine horns to themselves or other peritoneal organs. These studies clearly demonstrate that postoperative administration of recHirudin to the site of injury reduced the formation of postoperative adhesions in two animal models.