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 by 31P-NMR spectroscopy. Normoxic function, phosphate metabolite levels, and cytosolic free energy state (delta GATP) 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 GATP 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 GATP was consistently depressed in aged v mature hearts, Impaired recovery of delta GATP was 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 delta GATP [inorganic phosphate], [Mg2+]i [Na+] and [Ca2+]; and (iii) increased purine catabolism may contribute to poor metabolic recovery in aged hearts.
Headrick
J P
JP
Rotary Center for Cardiovascular Research, Griffith University Gold Coast, Southport, QLD, Australia.
D000375:Aging / Q000502:physiology*; D000818:Animals; D002412:Cations; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007477:Ions; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen; D011687:Purines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002412:Cations; D007477:Ions; D011687:Purines; D003402:Creatine Kinase; D010100:Oxygen