PREVENTION OF RETHROMBOSIS AFTER CORONARY THROMBOLYSIS IN A CHRONIC CANINE MODEL .1. ADJUNCTIVE THERAPY WITH MONOCLONAL-ANTIBODY 7E3 F(AB')(2) FRAGMENT

We examined the efficacy of the monoclonal antibody (MoAb) 7E3 F(ab')( 2) fragment, an inhibitor of the platelet glycoprotein (GP)IIb/IIIa re ceptor, to prevent coronary artery rethrombosis after successful throm bolysis with rt-PA. The circumflex coronary artery of anesthetized dog s was instrumented with a flow probe, an electrode, and a stenosis. Af ter recovery from the surgical procedure, the animals were reanestheti zed on postoperative day 9, and vessel wail injury was induced with cu rrent applied to the intimal surface of the circumflex coronary artery . The resulting occlusive thrombus was aged for 30 min, and recombinan t tissue plasminogen activator (rt-PA) was administered. The animals w ere allocated to receive either placebo or a single dose of 7E3 [0.8 m g/kg intravenous (i.v.) bolus] as the sole adjunctive agent. Ex vivo p latelet function and coronary artery blood flow velocity were recorded on each of 5 consecutive days. Reocclusion and mortality were reduced significantly in animals treated with 7E3 as compared with the placeb o-treated group. Significant inhibition of ex vivo platelet aggregatio n persisted for 48 h after a single injection of 7E3. The MoAb 7E3 F(a b')(2) fragment is effective as the sole adjunctive agent with rt-PA f or prevention of rethrombosis. The present study is unique in that it examined the efficacy of GPIIb/lIIa inhibition in an experimental mode l for an extended time, demonstrating the duration of antiplatelet the rapy required to prevent rethrombosis after thrombolysis.