The protease inhibitor gabexate mesilate in experimentally-induced acute pancreatitis with early gram-negative infection in the G?ttingen minipig: therapeutic efficacy and effects on blood coagulation and fibrinolysis

Due to its biochemical properties, the newly developed low-molecular protease inhibitor gabexate mesilate is assumed to be efficient in the treatment of complicated acute pancreatitis. This thypothesis was tested using the model of the experimental taurocholate pancreatitis with early artificial E. coli infection in G?ttingen mini pigs. Either gabexate mesilate or a placebo was given intravenously 150 min after induction of pancreatitis in a dosage of 2 mg/kg b.w. and h. Median survival time was 15 h in the gabexate mesilate treated animals (n = 7) as compared to 34 h in the placebo group (n = 7); this difference was not significant. The application of gabexate mesilate had no influence on the increased coagulation activity (decrease of prothrombin time, antithrombin III and platelet count) nor on the additional hyperfibrinolysis with concomitant decrease of plasminogen and antiplasmin. Prothrombin time and antithrombin III were less distinctly decreased in the placebo group; decrease of platelet count was more pronounced. On the basis of this study the hypothesis is not confirmed that treatment with gabexate mesilate for necrotizing experimental pancreatitis with additional gram-negative infection has a therapeutic efficiency.