Coronary reperfusion by thrombolysis and early beta-adrenergic blockade in acute experimental myocardial infarction

AbstractThe effects of beta-adrenergic blockade, thrombolysis and their combination on infarct size and left ventricular function were investigated in a canine model of thrombotic occlusion of the left anterior descending coronary artery. Metoprolol was administered intravenously (0.5 mg/kg) over 10 min, starting 15 min after occlusion. Recombinant human tissue-type plasminogen activator (rt-PA) was given intravenously 1 h after occlusion for clot lysis. Anatomic infarct size was measured as a percent of perfusion area and ventricular mass. Left ventricular function was assessed by ejection fraction and the centerline method.Groups 1, 3, 5 and 7 were evaluated after 24 h and received, respectively, metoprolol plus rt-PA, rt-PA, metoprolol and no treatment; groups 2, 4, 6 and 8 were studied after 1 week and treated, respectively, as groups 1, 3, 5 and 7. Metoprolol did not influence infarct size and global or regional ventricular function after 24 h and 1 week. Thrombolysis reduced infarct size from 69.5 ± 3.4% (24 h) and 76.6 ± 1.8% (1 week) in the control group to, respectively, 44.1 ± 11.6% and 39.5 ± 10.5% (p > 0.05), did not influence left ventricular function after 24 h and was accompanied after I week by a definite recovery of global and regional left ventricular function when compared with findings in control dogs. Metoprolol plus rt-PA further reduced infarct size (percent perfusion area) to 20.4 ± 3.7% and 19.9 ± 8.1% after 24 h and 1 week, respectively (p = NS versus rt-PA). After 24 h, a significant early recovery of global and regional left ventricular function was present; this better recovery persisted after 1 week.It is concluded that early administration of metoprolol plus rt-PA enhances the effects of thrombolysis on infarct size and left ventricular function after 24 h and 1 week