Circulation, Vol 77, 670-677, Copyright © 1988 by American Heart Association
HK Gold, BS Coller, T Yasuda, T Saito, JT Fallon, JL Guerrero, RC Leinbach, AA Ziskind and D Collen
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)
ARTICLES
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
Cardiac Division, Massachusetts General Hospital, Boston 02114.
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