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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.(ABSTRACT TRUNCATED AT 250 WORDS)

circulation

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.