Aging impairs functional, metabolic and ionic recovery from ischemia-reperfusion and hypoxia-reoxygenation

Functional and metabolic responses to ischemia-reperfusion and hypoxia-reoxygenation were studied in Langendorff perfused hearts from mature (2-4 months) and aged (18-24 months) Wistar rats. Hearts were subjected to 20 min global ischemia or hypoxia followed by 30 mill reperfusion or reoxygenation. Cellular metabolism was assessed by P-31-NMR spectroscopy. Normoxic function, phosphate metabolite levels. and cytosolic free energy state (Delta G(ATP)) were comparable in both age groups, although free [5'-AMP] and purine efflux were elevated in aged hearts. There were no aging-related differences in phosphate metabolite levels, pH or Delta G(ATP) during ischemia or hypoxia. Nevertheless, ischemic and hypoxic contracture tended to be higher in aged hearts. After reperfusion, heart rate x left-ventricular pressure recovered to 55% of pre-ischemia in mature hearts, and only 25% in aged hearts. After reoxygenation. function recovered to 75% in mature hearts and 55% in aged hearts. Recoveries of cellular [ATP], [phosphocreatine], [inorganic phosphate] and [Mg2+] were impaired, and Delta G(ATP) was consistently depressed in aged v mature hearts, Impaired recovery of Delta G(ATP) was associated with enhanced purine efflux in aged hearts. Post-ischemic Na+ and Ca+ accumulation was also increased by 30-40% in aged hearts. Tissue damage assessed by post-ischemic creatine kinase efflux was modest in mature hearts (<2% total tissue activity) and was 2.5-fold higher in aged hearts, The data show that: (i) aging reduces contractile recovery from ischemia/hypoxia; (ii) this is unrelated to the metabolic insult during ischemia/hypoxia, but parallels reduced recovery of Delta G(ATP) [inorganic phosphate], [Mg2+](i) [Na+] and [Ca2+]: and (iii) increased purine catabolism may contribute to poor metabolic recovery in aged hearts. (C) 1998 Academic Press.