PYRUVATE ENHANCES RECOVERY OF RAT HEARTS AFTER ISCHEMIA AND REPERFUSION BY PREVENTING FREE-RADICAL GENERATION

Pyruvate protects myocardium from ischemic and anoxic injury, effects that have been attributed to beneficial metabolic alterations. Pyruvate also reacts with hydrogen peroxide in vitro, and pyruvate prevents free radical injury in other organs. Hearts supplied with 2 mM of pyruvate with glucose during reperfusion recovered significantly more mechanical function (81%) than those provided with 2 mM of acetate (which does not react with free radicals) and glucose (49%) or glucose alone (27%). Pyruvate significantly reduced free radical generation during reperfusion as measured with electron spin resonance using the spin-trap 5,5-dimethyl-1-pyrroline-1-oxide. In a model of direct oxidant stress, hearts were perfused with 0.28 mM of hydrogen peroxide. In this model, loss of function was almost entirely prevented by addition of 2 mM of pyruvate. From these results we conclude an important mechanism of protection when pyruvate is supplied during reperfusion is limitation of oxygen-derived free radical damage.