EFFECTS OF AMINO-ACIDS ON SUBSTRATE SELECTION, ANAPLEROSIS, AND LEFT-VENTRICULAR FUNCTION IN THE ISCHEMIC-REPERFUSED RAT-HEART

The effect of aspartate and glutamate on myocardial function during re perfusion is controversial. A beneficial effect has been attributed to altered delivery of carbon into the citric acid cycle via substrate o xidation or by stimulation of anaplerosis, but these hypotheses have n ot been directly tested. C-13 isotopomer analysis is well suited to th e study of myocardial metabolism, particularly where isotopic and meta bolic steady state cannot be established. This technique was used to e valuate the effects of aspartate and glutamate (amino acids, AA) on an aplerosis and substrate selection in the isolated rat heart after 25 m in of ischemia followed by 30 or 45 min of reperfusion. Five groups of hearts (n = 8) provided with a mixture of [1,2-C-13]acetate, [3-C-13] lactate, and unlabeled glucose were studied: control, control plus AA, ischemia followed by 30 min of reperfusion, ischemia plus AA followed by 30 min of reperfusion, and ischemia followed by 45 min of reperfus ion. The contribution of lactate to acetyl-CoA was decreased in postis chemic myocardium (with a significant increase in acetate), and anaple rosis was stimulated. Metabolism of C-13-labeled aspartate or glutamat e could not be detected, however, and there was no effect of AA on fun ctional recovery, substrate selection, or anaplerosis. Thus, in contra st to earlier reports, aspartate and glutamate have no effect on eithe r functional recovery from ischemia or on metabolic pathways feeding t he citric acid cycle.