Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium

Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each) cardioplegia ameliorated cytosolic calcium ([Ca2+](i)) accumulation and was associated with enhanced functional recovery after surgically induced global ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic cytochrome oxidase I activity and mRNA levels, suggesting that enhanced functional recovery may involve the preservation of high-energy phosphates. To investigate this hypothesis, P-31 nuclear magnetic resonance was used to measure serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mg-f), and intracellular pH (pH(i)) in Langendorff-perfused, aged (135 Nk) rabbit hearts during preischemia, global ischemia (30 min), and reperfusion (30 min). K-MET cardioplegia retarded PCr depletion (P < 0.05) and significantly enhanced NTP preservation (P < 0.05) during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase in Mg-f during ischemia (P < 0.05). These results were correlated with amelioration of [Ca2+](i) accumulation during ischemia and preservation of left ventricular function after reperfusion and suggest that optimal functional recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the aged myocardium.