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.