Reduction of experimental adhesion formation by inhibition of plasminogen activator inhibitor type 1

Abstract

Background Adhesion formation is a common cause of complications following surgery. A reduction in peritoneal fibrinolytic capacity during operation is a key mechanism in the early formation of adhesions. An increase in the main inhibitor of fibrinolysis, plasminogen activator inhibitor type 1 (PAI-1), is a major factor in the loss of fibrinolytic activity. The aim of this study was to investigate if inhibition of PAI-1 could reduce the formation of adhesions after surgery. Methods Mice (n = 53) were subjected to a standard surgical procedure in order to induce adhesion formation to the abdominal side wall. At the conclusion of the operation, fragments for antigen binding of polyclonal rabbit antibody against PAI-1 (PRAP-1) were injected intraperitoneally, at two different concentrations. Control animals received an equal volume of the vehicle (saline). One week after operation adhesion formation was quantified. Results Both doses of PRAP-1 significantly reduced adhesion formation compared with the saline control (P = 0·003 and P = 0·002). There were no signs of bleeding in the postoperative period or at reoperation. Conclusion The present observations lend further support to the hypothesis of a pivotal role of fibrinolysis in the early formation of adhesions, and open up new possibilities for adhesion reduction by inhibiting PAI-1.