Function and Metabolism of Dog Heart in Ischemia and in Subsequent Reperfusion: Effect of Exogenous Glutamic Acid

The effect of intravenous infusion of glutamic acid on cardiac contractile function during short-term ischemia and subsequent reperfusion was studied in anaesthetized dogs. Left ventricular ischemia was induced by underperfusion of the anterior descending and circumflex coronary arteries. Infusion of glutamic acid at 3 mg/kg/min resulted in less depression of cardiac function when given after a 2 min period of 60% coronary blood flow reduction: left ventricular systolic pressure decreased by 9% vs. 22%, dP/dt decreased by 16% vs. 29%, the double product (left ventricular systolic pressure by heart rate) was reduced by 16% vs. 31%. When reperfusion was carried out during glutamic acid infusion there was a significantly enhanced recovery in cardiac function. The augmentation of cardiac performance in ischemia and reperfusion caused by glutamic acid was not accompanied by changes in myocardial oxygen consumption. Glutamic acid uptake by the ischemic myocardium increased 2-fold during infusion. This led to cessation of ammonia release from the heart due to stimulation of glutamine synthesis, and an enhancement of alanine formation coupled with pyruvate uptake but it did not effect lactate production. However, glutamic acid infusion did not influence cardiac performance and metabolism under conditions of normal coronary flow. The results suggest that elevation of glutamate arterial concentration exerts a beneficial effect on ischemic heart. The mechanisms of the protective action are discussed.