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

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 thi s study was to investigate if inhibition of PAI-1 could reduce the formatio n of adhesions after surgery. Methods: Mice (n = 53) were subjected to a standard surgical procedure in o rder to induce adhesion formation to the abdominal side wall. At the conclu sion of the operation, fragments for antigen binding of polyclonal rabbit a ntibody against PAI-1 (PRAP-1) were injected intraperitoneally, at two diff erent concentrations. Control animals received an equal volume of the vehic le (saline). One week after operation adhesion formation was quantified. Results: Both doses of PRAP-1 significantly reduced adhesion formation comp ared 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.