The Thrombolytic Effects of Native Tissue-Type Plasminogen Activator (AK-124) on Experimental Canine Coronary Thrombosis

Abstract

To evaluate the thrombolytic effects of the native tissue-type plasminogen activator (t-PA), the authors used a thrombus model simulating clinical situa tions. The native t-PA (AK-124) was obtained from human-derived normal cells. Experimental canine coronary thrombosis was produced by partial con striction and endothelial denudation of the vessel. In 19 dogs, coronary occlu sive thrombus was produced. Three hours after total occlusion of the coronary artery with thrombus, the authors attempted the thrombolytic therapy in 16 dogs. Histologically, three-hour thrombus was composed of a mixture of platelet aggregates, fibrin, and blood cells. They infused 0.375 mg/kg t-PA intraven ously in 7 dogs and 20,000 IU/kg urokinase (UK) in 9. Coronary recanalization was achieved in 5 (71%) with t-PA infusion and 6 (67%) with UK infusion. Plasma fibrinogen levels decreased to 76% of preinfusion value in the dogs with t-PA infusion and to 34% in those with UK infusion. Coronary reocclusion oc curred in 2 dogs with t-PA and 3 with UK. Thus, the native t-PA (AK-124) can provide coronary thrombolysis without severe depletion of plasma fibrinogen levels.