Study on the Effect of Streptokinase-Activated Plasmin (Fibrinolysin) on Clots in Various Stages of Organization12

In previous studies (1, 4), a method was developed for the quantitative recording of the lysis of thrombi and emboli produced with I'31-labeled fibrinogen. Using this method, the in vivo fibrinolytic activity of human and bovine plasmin was demonstrated (2). Other proteolytic enzymes (crude pancreatic protease, trypsin, carboxypeptidase, papain and ficin) were ineffective in maximal tolerated doses (1, 3, 4). Literature on the therapeutic use of proteolytic enzymes has been reviewed (1, 2). In all previous experiments, treatment was started one-half hour after forming labeled clots in the experimental animals. The question arose whether plasmin treatment would be effective in dissolving organized clots and whether there is a correlation between degree of organization and plasmin-induced lysis. The preparations referred to as "plasmin " in this study actually contain a variety of enzymatic activities; they are fibrinolytic, proteolytic and are able to activate the fibrinolysin system. Presumably they represent a mixture of plasmin, plasmin-activator and free streptokinase. It is difficult to ascribe therapeutic activity to any one of these components. The purpose of these experiments is to study therapeutic indications and conditions for the preparations currently undergoing clinical trial. Labeled clots were produced in several veins of dogs at various time intervals. At the time of treatment, these clots were of various ages. Differences in lysis were established by recording