Branched-chain amino acids (BCAAs) are oxidative energy substrates for the heart and may exert anabolic effects on myocardial protein. The factors regulating their myocardial uptake in patients with ischemic heart disease are therefore of interest. To examine whether myocardial BCAA utilization is influenced by the circulating insulin concentration, in 10 patients with chronic ischemic heart disease, we measured transmyocardial amino acid balance during fasting and again during a 90-minute euglycemic insulin infusion (plasma insulin, 218+/-25 microU x mL(-1)) with plasma BCAA concentrations held constant by coinfusion. In the fasting state, the myocardial fractional extraction of leucine (8%), isoleucine (9%), and valine (5%) from arterial plasma was slightly greater than that of glucose (3%), while net myocardial BCAA uptake (leucine, 409+/-207 nmol x min(-1); isoleucine, 220+/-144 nmol x min(-1); valine, 407+/-326 nmol x min(-1); and total BCAA uptake, 1.0+/-0.3 micromol x min(-1)) was about 13% that of glucose (8+/-2 micromol x min(-1)). During euglycemic hyperinsulinemia, myocardial glucose uptake increased 3-fold, but there was no change in the arterial-coronary sinus balance or net myocardial uptake of any BCAA under conditions where their plasma concentrations were held constant. Instead, the myocardial uptake of each BCAA correlated positively with its concentration in arterial plasma. These results demonstrate that in patients with cardiovascular disease, myocardial utilization of BCAAs is insensitive to the circulating insulin level and is regulated instead by their availability in arterial plasma. Hyperinsulinemia reduced the magnitude of both net glutamate uptake and alanine release, suggesting a possible salutary effect on myocardial oxidative efficiency.