Prevention of rethrombosis after coronary thrombolysis in a chronic canine model. II. Adjunctive therapy with r-hirudin

We examined the effectiveness of the direct-acting thrombin inhibitor, recombinant hirudin (r-hirudin), for prevention of coronary rethrombosis after thrombolysis with recombinant tissue plasminogen activator (rt-PA) in a canine model of coronary artery thrombosis. The reocclusion rate of 15-30% associated with thrombolytic therapy emphasizes the need for adjunctive therapy to prevent rethrombosis. We studied r-hirudin for its potential to prevent reocclusion in a model of coronary artery thrombosis/thrombolysis. The circumflex coronary arteries of anesthetized dogs were instrumented with a flow probe, an intraluminal electrode, and a ligature stenosis. The dogs were reanesthetized on the ninth postoperative day, and intimal injury was induced with an anodal current. After occlusive thrombus formation, tissue plasminogen activator (rt-PA) was administered. The animals were allocated to receive either placebo, r-hirudin [5 mg/kg intravenously (i.v.) bolus, 2 mg/kg/h i.v., for 3.5 h] 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 function and coronary artery blood flow velocity were recorded on each of 5 consecutive days. Infarct size and residual thrombus weight were determined at the end of the protocol. r-Hirudin infusion (3.5 and 12 h) provided little benefit over rt-PA alone. Ex vivo platelet aggregation was not affected by r-hirudin. Little improvement in the incidence of reocclusion and mortality in a model of coronary artery thrombosis/thrombolysis resulted from adjunctive treatment with r-hirudin.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Canine coronary thrombosis/thrombolysis model showed that r-hirudin (5 mg/kg bolus + 1–2 mg/kg/h for 3.5 to 12 h) without aspirin/heparin provided only minor benefit over rt-PA alone in preventing reocclusion.

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