Urokinase-mediated Thrombolysis: A Dose-Response Relationship in Cats Work in Progress☆

A cat model was developed to study thrombolytic agents. The infrarenal aorta was surgically exposed, all side branches were ligated, and both ends of the segment were occluded. After preformed clot was injected into the segment, proximal flow was restored and a distal stenosis was created. Urokinase was infused at rates varying from 4,000 to 250,000 U/h. Amount of remaining clot was quantified every 15 minutes with cine angiography. Pre- and postinfusion measurements of prothrombin time, partial thromboplastin time, thrombin time, and levels of fibrinogen and fibrin degradation products were obtained. A graph of thrombolysis rate versus infusion rate was obtained yielding maximal thrombolytic activity at 126,000 U/h and 90% of maximal activity at an infusion rate of 70,000 U/h. Levels of fibrin degradation products did not change. Prothrombin, partial thromboplastin, and thrombin times increased with increasing infusion rates, leveling off at 100,000 U/h, while fibrinogen levels decreased, with a plateau at 50,000 U/h.