COMPARISON OF HIRUDIN AND HEPARIN AS ADJUNCTS TO STREPTOKINASE THROMBOLYSIS IN A CANINE MODEL OF CORONARY-THROMBOSIS

Recombinant desulfatohirudin (HI), a potent and specific thrombin inhi bitor, was compared with heparin (HE) as an adjunct to streptokinase t hrombolysis. In pentobarbital-anesthetized dogs, an occlusive thrombus (whole blood+thrombin) was introduced into the left anterior descendi ng coronary artery (LAD) with superimposed endothelial damage and dist al high-grade stenosis. Intravenous infusion of saline (vehicle), HI ( 0.3 mg/kg followed by 0.3 mg/kg per hour, 1 mg/kg followed by 1 mg/kg per hour, or 2 mg/kg followed by 2 mg/kg per hour), or HE (60 units/kg followed by 40 units/kg per hour or 100 units/kg followed by 60 units /kg per hour) was initiated 15 minutes before streptokinase (750,000 u nits for 60 minutes) administration. Vessel patency was monitored for 180 minutes after streptokinase administration with a volume How probe on the proximal LAD. In dogs treated with no adjunctive agent (saline control), none of the vessels were recanalized with streptokinase. Bo th HI and HE promoted reperfusion, inhibited reocclusion, and reduced the residual thrombus mass in a dose-dependent fashion. However, at co mparable levels of therapeutic anticoagulation (activated partial thro mboplastin time [APTT] = 1.5-2.0 times baseline) HI exhibited a higher incidence of reperfusion (eight of eight dogs [100%] versus one of ei ght dogs [12%]), a shorter time to reperfusion (33+/-6 versus 59 minut es), a longer duration of initial reperfusion (106+/-21 versus 10 minu tes), and a smaller residual thrombus mass than did HE. Likewise, the slope of the relation between the APTT prolongation and the total repe rfusion time (''anticoagulation/antithrombosis profile'') was almost f ive times higher for the combined HI data than for the HE data. Our re sults indicate that HI is more effective than HE in enhancing and sust aining coronary recanalization with streptokinase at a HI dose that mo destly prolongs coagulation time and does not alter bleeding times.