Enhanced mechanical recovery of anoxic and ischemic myocardium by amino acid perfusion

Abstract

Effects of amino acids on the fall of developed tension during anoxic and ischemic stresses and the recovery during reoxygenation/reperfusion were measured in isolated arterially perfused interventricular rabbit septa. Control septa received no amino acids. Treated septa received 1 amino acid. Amino acids did not influence prestress developed tension. The L-isomers of arginine, glutamate, ornithine and aspartate significantly maintained developed tension during a apnoxia and enhanced mechanical recovery by approximately 2-fold following anoxic and ischemic stresses. D-Arginine was less effective than the L-isomer. The L-isomers of glycine, methionine and glutamine were ineffective. Perfusion with arginine for 3 min before ischemia or introduction upon reperfusion was sufficient to enhance recovery. Supplying glutamate only during the middle 50 min of a 60 min anoxic stress did not decrease the protection by the amino acid. Glucose was not necessary for the protection during the anoxic stress. Aminooxyacetic acid (2 mM), an inhibitor of cytosolic and mitochondrial transaminases, completely eliminated the enhanced recovery produced by glutamate. Simple substrate availability, increased synthesis of proteins or adenine nucleotides, and intracellular buffering are not supported as the mechanism of the protection. The hypothesis that the protective amino acids act through anaerobic intermediary metabolic reactions is supported.