A model system for the in vivo determination of the thrombolytic effect of plasminogen activators.

An in vivo model system for measuring the thrombolytic efficiency of plasminogen activators was used. The formation of radiolabelled microthrombi was induced by infusion with I-125 labelled fibrinogen and thrombin. Reactive fibrinolysis was inhibited by administration of suboptimal levels of e-aminocaproic acid. The thrombolytic and subsequent fibrinolytic events were followed in the capillary bed of the lungs of anesthetized rats by external monitoring of the I-125 activity over the lung field. The model was successfully employed to demonstrate the thrombolytic effect of plasminogen activator produced by a transplanted spontaneous rat prostate adenocarcinoma cell line (PA III). The system proved to be reproducible with detection limits of 6000 I.U. using the PA-III cell line derived activator.