Tissue repair in presence of locally applied inhibitors of fibrinolysis

The effects of protease inhibitors on tissue repair was studied by incorporation of inhibitor preparations in homologous plasma clots implanted subcutaneously in the rat. The two inhibitor preparations, one isolated from bovine lung tissue and another prepared from raw peanuts, differed markedly in purity and content of contaminating proteins. The influence on tissue repair was uniform. The inhibitors enhanced formation of connective tissue with increased tensile strength of the wound tissue. Vascularization was delayed. Presence of inhibitors prevented the demonstration of fibrinolytically active sites except at the later stages (3-4 weeks), when the repair process approached the pattern of the controls. There was only insignificant lysis related to leukocytic immigration. There was no marked foreign body reaction. The results support the concept that fibrinolytic activity, caused by the local release of plasminogen activator, assists in the regulation of reparative connective tissue formation.