Antithrombotic benefit of subendothelium-bound urokinase: an experimental study

To improve the outcome of extremity replantation, microsurgeons have administered systemic antithrombotic agents (e.g., heparin, aspirin, dextran). To obviate the risks associated with systemic anticoagulation, we have investigated the use of topically applied urokinase for its binding capacity to arterial subendothelium and for its ability to prevent subsequent thrombosis. An arterial model of thrombosis associated with intimal deendothelialization was developed. Donor rat carotid arteries were everted and mechanically deendothelialized with a scalpel blade. The vessels were next subjected to one of several treatments, which included 30-minute incubation with urokinase, heparin, or vehicle (lactated Ringer's solution). The vessels were then washed, reinverted to normal orientation, sectioned into 5 mm lengths, and grafted into the femoral arteries of recipient rats. Two-hour patency rates were 25% for controls (n = 20), 10% for heparin-treated vessels (n = 10), and 55% for urokinase-treated vessels (n = 20); this last was significantly greater than the other two groups. In vitro investigations revealed that urokinase has a high capacity for binding to subendothelium, with a release half-life of approximately 20 minutes. Surface-bound urokinase was found to have proteolytic activity similar to that of urokinase in solution. These results indicate that urokinase may be a more beneficial irrigating solution additive than heparin for repair of traumatized vessels.