Interaction of hypoxia and aging in the heart: analysis of high energy phosphate content

To test the hypotheses that aged myocardium has lower ATP concentration and that a greater ATP hydrolysis during hypoxia exaggerates diastolic dysfunction in aged myocardium, we used 31P NMR spectroscopy to measure ATP and phosphocreatine (PCr) contents combined with heart function at baseline and during hypoxia and reoxygenation in perfused hearts isolated from young adult (3-4 months old) and old (24-25 months old) Fisher 344 rats. At baseline, old hearts had 30% lower heart rate and prevalent supraventricular arrhythmia; they had lower PCr and creatine contents (approximately 30%) but normal ATP content. Hypoxia caused similar decreases in heart rate and rate pressure product in young and old hearts. There was a two-fold increase in left-ventricular end-diastolic pressure (LVEDP) in young adults, but, surprisingly, no change in LVEDP in old hearts. ATP decreased similarly in hearts from young and old rats, but the PCr decrease was two-fold smaller in old hearts during hypoxia. Superimposition of pacing on hypoxic old hearts caused six-fold increase in LVEDP; although utilization of PCr increased, it was still incomplete. We conclude that PCr is incompletely used to maintain ATP level during hypoxia especially in the senescent heart, and that the increase in LVEDP in old hearts cannot be explained solely by changes in indices of bioenergetics.