SUSTAINED INHIBITION OF THE VESSEL WALL PLATELET INTERACTION AFTER DEEP CORONARY-ARTERY INJURY BY TEMPORARY INHIBITION OF THE PLATELET GLYCOPROTEIN IIB IIIA RECEPTOR

Background: There purpose of this investigation was to determine whether a vascular surface overlying deep arterial injury could become nonthrombogenic after temporary, but complete, inhibition of platelet reactivity. Methods: The circumflex coronary arteries of 18 dogs were instrumented with a Doppler flow probe and subjected to an intracoronary stimulation electrode and a ligature stenosis. One day later, group 1 animals received placebo and group 2 animals received an intravenous injection of the 7E3 F(ab')2 monoclonal antibody (0.8 mg/kg) to the platelet glycoprotein llb/llla receptor. A deep electrolytic injury of the coronary artery was then produced by applying a 100-mu-A direct anodal current to the intimal surface of the vessel for 3 hours. Results: Compared with group 1, thrombotic arterial occlusion in group 2 was reduced significantly at 3 hours (6/9 vs 0/9, P = 0.01), at 24 hours (9/9 vs 0/9, P = 0.001), and after 6 days (9/9 vs 2/9, P = 0.01). Mortality was reduced in group 2 at 8 hours (5/9 vs 0/9, P = 0.035), at 24 hours (9/9 vs 0/9, P = 0.001), and after 6 days (9/9 vs 1/9, P = 0.001). Myocardial infarction occurred more frequently in group 1 (9/9 vs 4/9, P = 0.05). Infarct size, expressed as a percent of left ventricular mass was larger in group 1 (18.9% +/- 3.4% vs 7.9% +/- 3.3%, P = 0.07). Platelet aggregation to arachidonic acid was inhibited completely for at least 3 hours in group 2 and did not return to normal until day 4. Conclusions: Inhibition of in vivo platelet aggregation with the 7E3 F(ab')2 monoclonal antibody prevented acute coronary artery occlusion and reduced the incidence of late thrombotic occlusion, infarct size, and mortality. Interaction of the injured vascular wall with circulating platelets is a time-limited event, with the vessel becoming relatively nonthrombogenic despite extensive damage to the intimal and subintimal structures and a progressive return of platelet reactivity.