RESTORATION OF CORONARY FLOW IN MYOCARDIAL-INFARCTION BY INTRAVENOUS CHIMERIC 7E3 ANTIBODY WITHOUT EXOGENOUS PLASMINOGEN ACTIVATORS - OBSERVATIONS IN ANIMALS AND HUMANS

Background Corollary thrombus is composed of platelets and fibrin, and during thrombolytic treatment, reflow may be slowed by platelet depos ition. It may be possible to initiate coronary reflow without exogenou s plasminogen activators by blocking platelet aggregation while fibrin generation is impeded with heparin. Methods and Results In 14 dogs, l eft anterior descending coronary artery thrombosis was produced by end othelial trauma and thrombin instillation in the presence of stenosis distally. Reflow was monitored by flow probe during treatment with (1) heparin, (2) heparin and aspirin, and (3) heparin, aspirin, and intra venous 7E3. Eighty percent of dogs treated with the third combination showed stable reflow (greater than or equal to 25% of prestenotic flow ) in 50+/-9 minutes. In addition, 13 patients were studied during intr avenous administration of c7E3 10 minutes before primary angioplasty f or acute myocardial infarction and Thrombolysis In Myocardial Infarcti on (TIMI) grade 0 or 1 flow. Pretreatment included heparin and oral as pirin. Flow increased during a 10-minute period by at least one TIMI g rade in 11 (85%) of 13 and reached TIMI grade 2 or 3 in 7 (54%) of 13 patients. Average TIMI grade flow increased from 0.31+/-0.5 to 1.54+/- 0.8 (P<.001). Thrombus length 10 minutes after c7E3 was 5.1+/-3.5 mm. All but 1 patient then underwent angioplasty. There were no complicati ons. Conclusions Coronary reflow can be initiated by intravenous 7E3 a dministration in the presence of heparin and aspirin. In human patient s, this flow can be observed in 10 minutes without exogenous thromboly tic agents.