PREVENTION OF RETHROMBOSIS AFTER CORONARY THROMBOLYSIS IN A CHRONIC CANINE MODEL .2. ADJUNCTIVE THERAPY WITH R-HIRUDIN

We examined the effectiveness of the direct-acting thrombin inhibitor, recombinant hirudin (r-hirudin), for prevention of coronary rethrombo sis after thrombolysis with recombinant tissue plasminogen activator ( rt-PA) in a canine model of coronary artery thrombosis. The reocclusio n rate of 15-30% associated with thrombolytic therapy emphasizes the n eed for adjuctive therapy to prevent rethrombosis. We studied r-hirudi n for its potential to prevent reocclusion in a model of coronary arte ry thrombosis/thrombolysis. The circumflex coronary arteries of anesth etized dogs were instrumented with a flow probe, an intraluminal elect rode, and a ligature stenosis. The dogs were reanesthetized on the nin th postoperative day, and intimal injury was induced with an anodal cu rrent. After occlusive thrombus formation, tissue plasminogen activato r (rt-PA) was administered. The animals were allocated to receive eith er placebo, r-hirudin [5 mg/kg intravenously (i.v.) bolus, 2 mg/kg/h i .v., for 3.5 hi or r-hirudin (5 mg/kg i.v., bolus, 1 mg/kg/h i.v., for 12 h). Neither aspirin nor heparin was used. Ex vivo platelet functio n and coronary artery blood flow velocity were recorded on each of 5 c onsecutive days. Infarct size and residual thrombus weight were determ ined at the end of the protocol. r-Hirudin infusion (3.5 and 12 h) pro vided little benefit over rt-PA alone. Ex vivo platelet aggregation wa s not affected by r-hirudin. Little improvement in the incidence of re occlusion and mortality in a model of coronary artery thrombosis/throm bolysis resulted from adjunctive treatment with r-hirudin.