Previous studies showed that tolmetin administered as a single instillate intraperitoneally at the end of surgery can reduce adhesion formation. In this report, studies on the mechanism by which this occurs were conducted. The effects of tolmetin administered intraperitoneally on red (RBC) and white blood cell (WBC) number, macrophage and polymorphonuclear neutrophil infiltration, protease activity in lavage fluid, and the fibrinolytic activity of a biopsy of nonsurgical and traumatized peritoneal sidewall were examined. Tolmetin was shown to increase the number of RBC at one postoperative time point in rabbits, but not in rats. In addition, tolmetin administration elevated the number of WBC harvested from the peritoneum predominantly through an increase in macrophage number. Administration of tolmetin also modulated the level of protease and protease inhibitor activity in the lavage fluid harvested from the peritoneum. The most pronounced change was a decrease in the level of plasminogen activator inhibitor activity. In addition, acute administration of tolmetin to rats elevated the level of fibrinolytic activity at the site of trauma as measured by in vitro cultures. In summary, intraperitoneal administration of tolmetin, a nonsteroidal anti- inflammatory drug which reduces adhesion formation in both rats and rabbits, at the end of surgery modulated the number of WBCs in the peritoneal cavity and the protease and protease inhibitory activities present in the peritoneal lavage fluid and peritoneum after surgery.
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