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 min reperfusion or reoxygenation. Cellular metabolism was assessed by31P-NMR spectroscopy. Normoxic function, phosphate metabolite levels, and cytosolic free energy state (ΔGATP) 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 ΔGATPduring ischemia or hypoxia. Nevertheless, ischemic and hypoxic contracture tended to be higher in aged hearts. After reperfusion, heart rate ×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 ΔGATPwas consistently depressed in agedvmature hearts, Impaired recovery of ΔGATPwas associated with enhanced purine efflux in aged hearts. Post-ischemic Na+and Ca2+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 ΔGATP[inorganic phosphate], [Mg2+]i[Na+] and [Ca2+]; and (iii) increased purine catabolism may contribute to poor metabolic recovery in aged hearts.