INTRAVENOUS ADMINISTRATION OF THE GLYCOPROTEIN IIB-IIIA RECEPTOR ANTAGONIST 7E3 INDUCES REPERFUSION OF AN ACUTE THROMBOTIC OCCLUSION OF THECANINE CORONARY-ARTERY

The ability of the F(ab')(2) fragment of the murine monoclonal antibod y 7E3 directed against the platelet glycoprotein IIb-IIIa receptor com plex, to cause reperfusion of a totally occluding coronary artery thro mbus was examined alone and in combination with aspirin and heparin in a canine model of coronary artery thrombosis. A localized thrombus wa s produced in the left circumflex coronary artery in open-chest dogs b y electrolytic injury of the endothelium, Intravenous administration o f a single injection of 5.0 mg/kg aspirin and heparin (80 U/kg bolus p lus 30 U/kg/hrx2hr) maintained vessel patency for approximately 101+/- 15 minutes. After vessels had been completely occluded for 5 minutes ( in the presence of aspirin + heparin), a single intravenous injection of saline (10 ml) or 0.8 mg/kg 7E3 was administered. Reperfusion was o bserved in all dogs (6 of 6) receiving 7E3; 4 of 6 dogs maintained ves sel patency throughout the course of the 2 hour observation period. Ac tivated partial thromboplastin and thrombin times were elevated 1.4 an d 9 fold, respectively, in groups that received heparin. Template blee ding times were significantly elevated in the groups receiving 7E3. In the control group, 2 of 5 dogs reperfused briefly, however neither we re patent at the end of the observation period. A third group of 4 dog s which did not receive the aspirin+heparin regimen was allowed to occ lude and 5 minutes later received a single intravenous injection of 0. 8 mg/kg 7E3. None of the 4 dogs in this group reperfused at any time d uring the study. There were no significant differences between groups in regards to hematological or hemodynamic measurements during the exp eriment. We concluded from these findings that the monoclonal antibody , 7E3 can promote the dissolution of friable coronary artery thrombi t hat evolve during standard anticoagulant and antiplatelet therapy. (C) 1998 Elsevier Science Ltd.