Efficacy of tissue plasminogen activator and urokinase in a canine model of prosthetic graft thrombosis.
Tissue plasminogen activator and urokinase were evaluated in a model of prosthetic graft thrombosis. In addition, the effects of thrombus age on lysability and the effect of thrombolytic agents on endothelium were examined. Polytef (polytetrafluoroethylene [PTFE]) grafts (3 mm X 3.5 cm) were placed in femoral arteries of dogs and graft thrombosis was induced. Grafts were treated with a local infusion of either urokinase or tissue plasminogen activator (4000 units/min) and the times for initial flow, complete thrombolysis, and anastomotic bleeding were noted. The luminal surfaces of the grafts and the proximal arterial segments were assayed for the production of thromboxane A2 and prostacyclin and examined with scanning electron microscopy. No difference in the ease of graft lysis was observed, but 50% of tissue plasminogen activator-treated vs 0% of urokinase treated grafts had extravasation of blood through the wall. Grafts treated with tissue plasminogen activator produced less thromboxane A2 and had less thrombus than those treated with urokinase. No differences between arteries exposed to either agent and control arteries were seen. Grafts treated 1,3,5, and 7 days after thrombosis were progressively more difficult to lyse. We conclude that tissue plasminogen activator is an effective thrombolytic agent, but has a potential for local bleeding complications. Grafts of PTFE are thrombogenic after lysis, but may be less so with tissue plasminogen activator than with urokinase. No effect on arterial endothelium was seen, and our studies confirm the clinical impression that older thrombi are more difficult to lyse.
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D004195:Disease Models, Animal; D004285:Dogs; D011464:Epoprostenol / Q000096:biosynthesis; D006083:Graft Occlusion, Vascular / Q000188:drug therapy*; D006470:Hemorrhage / Q000139:chemically induced; D008855:Microscopy, Electron, Scanning; D011138:Polytetrafluoroethylene; D013927:Thrombosis / Q000188:drug therapy*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
D013928:Thromboxane A2; D011138:Polytetrafluoroethylene; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator