Evaluation of epithelial tissue plasminogen activator as a thrombolytic agent in a rabbit model of venous thrombosis

The thrombolytic effect of guinea pig keratocyte plasminogen activator was evaluated in rabbits with experimental jugular vein thrombosis and compared with human melanoma activator. Both the activators were infused locally at two dose levels in groups of three rabbits. Infusion of 6,000 and 16,000 I.U./rabbit over 4 hr resulted in 43 and 62% lysis with guinea pig keratocyte activator whereas melanoma activator induced 59 and 66% lysis with 6,000 and 12,000 I.U./rabbit. Thrombolysis with both these activators was not associated with systemic activation of the fibrinolytic system or fibrinogen breakdown. It is concluded that the guinea pig keratocyte activator is a specific thrombolytic agent with an in vivo potency very similar to the melanoma activator.