Simple canine model of arterial thrombosis with endothelial injury suitable for investigation of thrombolytic agents

Three separate studies were done to evaluate a new canine model of arterial thrombosis with endothelial injury. Endothelial injury was produced by exposing the luminal surface of a 2-cm segment of femoral artery to 100°C saline for 5 min. There was no disruption of proximal or distal blood flow with this model, and thrombolysis was continuously monitored by measuring ¹²⁵I-labelled fibrin gamma emissions from the thrombus. Study No. 1 showed that complete endothelial denudation was achieved with this model. Study No. 2 demonstrated 1) adherence of the experimentally induced thrombus to subendothelial connective tissue, and 2) endogenous thrombolysis of approximately 9% during the initial 2 h after thrombus formation. Study No. 3 tested the usefulness of the model for evaluating the thrombolytic efficacy of urokinase. Urokinase (30,000 U Kg, bolus IV injection) caused 38 ± 5.4% thrombolysis within 90 min of drug administration versus 5.9 ± 2.4% for a saline-treated control group. We conclude that this model provides a technically simple and reproducible method for the laboratory investigation of thrombosis and thrombolysis in arteries with endothelial injury.