Data show that uptake of amino acids correlates with myocardial oxygen consumption after aortic cross-clamp in humans; this suggests a direct link between amino acids and myocardial energy metabolism. The aim of this preliminary study was to investigate the anti-ischemic effects of immediate and long-term supplementation of an amino acid mixture. We tested this hypothesis on isolated rats hearts subjected to global ischemia for 30 minutes. Long-term treatment with an amino acid mixture achieved the following: (1) reduced the increase of diastolic pressure (48 +/- 3 mm Hg vs 21 +/- 4 mm Hg; p <0.05); (2) maintained the tissue content of adenosine triphosphate during ischemia (2.5 +/- 0.6 micromol/g wet wt [gww] vs 7.0 +/- 1.2 micromol/gww; p <0.05); and (3) improved the recovery of developed pressure at the end of postischemic reperfusion (11 +/- 2 mm Hg vs 38 +/- 3 mm Hg; p <0.05), reducing the release of creatine kinase (375 +/- 30 microU/min/gww vs 196 +/- 15 microU/min/gww; p <0.05) and lactate (15 +/- 1.5 mg/min/gww vs 5 +/- 1 mg/min/gww; p <0.05). We conclude that long-term supplementation of an amino acid mixture reduced myocardial ischemic damage.