Background: An optimal strategy to improve reperfusion in patients with arterial occlusions is a recognized clinical need. We hypothesized that hirudin (thrombin inhibitor) and S18886 [S18, thromboxane A(2) receptor (TP) antagonist] would improve blood flow and reperfusion rates after thrombolysis with the direct-acting fibrinolytic enzyme alfimeprase.
Methods: In anesthetized beagles, carotid artery thrombosis was induced by electrolytic endothelial injury. After 30 minutes of occlusion, animals were administered vehicle, hirudin, and/or S18. Carotid artery blood flow was monitored for 90 minutes after the infusion of alfimeprase or recombinant tissue plasminogen activator (rt-PA).
Results: The onset to reperfusion was more rapid in animals treated with alfimeprase than in those treated with rt-PA. All the animals treated with hirudin + S18 + alfimeprase maintained vessel patency, and all vehicle-treated animals reoccluded. In animals treated with hirudin + S18 + alfimeprase, time to reocclusion and total reflow time after thrombolysis were longer compared with vehicle-treated animals. The quality and quantity of blood flow were most improved in animals treated with hirudin + S18 + alfimeprase. There were no significant differences in time to reocclusion, total reflow time, and quality and quantity of blood flow between vehicle + rt-PA-treated animals and hirudin + S18 + rt-PA-treated animals.
Conclusions: Dual antithrombotic therapy with hirudin and S18 improves reperfusion after thrombolysis with alfimeprase but not rt-PA.