The amino acids aspartate and glutamate, in combination, were evaluated as a means of reducing infarct size and improving cardiac function during reperfusion in an intact pig having an acute anteroseptal infarct. Three groups of 6 pigs each were randomly studied in a blinded manner: control (no amino acids), aspartate/glutamate 3 mmol/L, and aspartate/glutamate 13 mmol/L. The left anterior descending coronary artery was occluded distal to its first diagonal branch for 60 minutes followed by reperfusion for 6 hours. Aspartate and glutamate were administered systemically immediately before reperfusion. The following parameters were measured: infarct size and percent area at risk, global metabolic function, global and regional myocardial function, and tissue parameters of metabolic function. The results clearly showed a significant decrease in infarct size from 60% of the area at risk in control pigs to 37% in both 3 mmol/L and 13 mmol/L amino acid groups. Cardiac output, coronary blood flow, and global oxygen consumption were not significantly affected by the use of amino acids relative to the control group. Global left ventricular mechanical function was also not adversely affected by the infarct and was not altered by amino acid administration. Regional function, however, was significantly decreased by occlusion of the left anterior descending coronary artery in all groups to near 20% and only significantly recovered to 64% in the 13 mmol/L amino acid group. Adenosine triphosphate and acetyl coenzyme A measurements documented significant increases in the 13 mmol/L amino acid group relative to the control group. The conclusions of this study strongly support aspartate/glutamate supplementation for stunned, reperfused myocardium. It is apparent that the effect of amino acid supplementation on glycolysis is directly translated into improved regional function and reduced infarct size.