Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion aftr reperfusion with recombinant tissue-type plasminogen activator in dogs

T. Yasuda, H. K. Gold, J. T. Fallon, R. C. Leinbach, J. L. Guerrero, L. E. Scudder, M. Kanke, D. Shealy, M. J. Ross, D. Collen, B. S. Coller

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219 Scopus citations

Abstract

Localized thrombosis was produced in the left anterior descending (LAD) coronary artery of open chest dogs by constricting a segment so as to produce > 90% stenosis (reducing blood flow to 40 ± 10% of baseline), and placing a thrombus in the segment immediately proximal to the stenosis by inducing endothelial cell injury and instilling a mixture of blood and thrombin. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 15-30μg/kg per min for 30 or 60 min in eight dogs induced coronary artery reperfusion within 23 ± 7 min (mean ± SD), but reocclusion occurred despite heparin anticoagulation in all but one of these dogs within 7 ± 5 min. Intravenous injection of 0.8 mg/kg of the F(ab')2 fragment of a monoclonal antibody (7E3) directed against the platelet GPIIb/IIIa receptor, prevented reocclusion in 10/10 dogs during an observation period of 2 h (P < 0.001 vs. rt-PA alone). The antibody abolished ADP-induced platelet aggregation and markedly prolonged the bleeding time. Intravenous aspirin or dipyridamole prevented reocclusion for 1 h or more in only 2/7 and 1/6 dogs, respectively. We conclude that the monoclonal antibody is very effective in preventing reocclusion after successful thrombolysis of occluded coronary arteries with rt-PA.

Original languageEnglish
Pages (from-to)1284-1291
Number of pages8
JournalJournal of Clinical Investigation
Volume81
Issue number4
DOIs
StatePublished - 1988
Externally publishedYes

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