This study was designed to test the hypothesis that beta-adrenergic receptor blockade with esmolol would decrease the hemodynamic and myocardial metabolic impairment produced by left anterior descending coronary artery (LADa) occlusion. Twenty-three anesthetized open-chest dogs underwent direct cannulation of the LADa, its companion vein (LADv), and a distal circumflex vein (CFXv) for blood sampling. All dogs were subjected to two consecutive 15-minute periods of total LADa occlusion; group 1 (n = 11) received an infusion of esmolol (150 micrograms.kg-1.min-1) during either occlusion period (randomly assigned) and group 2 (n = 12) received no intervention during either occlusion period. One hour of reperfusion was interposed between the two periods of LADa occlusion. Hemodynamic measurements were made and blood was sampled from the aorta, CFXv, LADa, and LADv before and during both periods of LADa occlusion. Without esmolol infusion, LADa occlusion was associated with decreases in stroke index, coronary perfusion pressure, and left ventricular stroke work index; with esmolol infusion these hemodynamic decrements did not occur. During both LADa occlusion periods in both groups, lactate extraction became negative, i.e., there was net lactate production. Despite this, the magnitude of lactate production was less with esmolol than without it. Finally, average endocardial-to-epicardial blood flow ratio in the LAD perfusion area was decreased during each LAD occlusion period except when esmolol was infused, during which the baseline value was maintained. Thus, infusion of esmolol during temporary LADa occlusion preserved certain hemodynamic variables, preserved the ratio of endocardial-to-epicardial blood flow, and decreased the apparent magnitude of lactate production.