Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GPIIb/IIIa antibody in a canine preparation

The effects of bolus injections of recombinant single-chain tissue-type plasminogen activator (rt-PA) and of F(ab')2 fragments of a murine monoclonal antibody (7E3) against the human platelet GPIIb/IIIa receptor [7E3-F(ab')2] on coronary arterial thrombolysis and reocclusion was studied in a canine preparation of coronary artery thrombosis superimposed on high-grade stenosis. Bolus intravenous injections of rt-PA at a dose of 0.45 mg/kg, repeated at 15 min intervals until reperfusion occurred (maximum of four injections) caused reperfusion in five of seven dogs within 100 min (33 +/- 15 min, mean +/- SD). Reperfusion was rapidly followed (generally within 10 min) by reocclusion and then by periods of cyclical reflow and reocclusion. A single intravenous injection of 7E3-F(ab')2 alone at 0.8 mg/kg caused reperfusion within 100 min in two of six dogs (19 and 37 min) without subsequent reocclusion. Single bolus injections of different amounts (0.1 to 0.8 mg/kg) of 7E3-F(ab')2 were then combined with bolus injections of 0.45 mg/kg of rt-PA. Stable reperfusion without reocclusion was accomplished with 0.8 or 0.6 mg/kg 7E3-F(ab')2 and a single injection of 0.45 mg/kg rt-PA within 6 +/- 3 min (n = 6, p less than .01) and 8 +/- 5 min (n = 5, p less than .02), respectively. None of these animals suffered reocclusion of the coronary artery. Lower doses (0.1 to 0.2 mg/kg) of 7E3-F(ab')2 did not significantly shorten the time to reperfusion and did not prevent reocclusion.