INTERACTION OF HYPOXIA AND AGING IN THE HEART - ANALYSIS OF HIGH-ENERGY PHOSPHATE CONTENT

To test the hypotheses that aged myocardium has lower ATP concentratio n and that a greater ATP hydrolysis during hypoxia exaggerates diastol ic dysfunction in aged myocardium, we used P-31 NMR spectroscopy to me asure ATP and phosphocreatine (PCr) contents combined with heart funct ion at baseline and during hypoxia and reoxygenation in perfused heart s 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 an d prevalent supraventricular arrhythmia; they had lower PCr and creati ne contents (similar to 30%) but normal ATP content. Hypoxia caused si milar decreases in heart rate and rate pressure product in young and o ld hearts. There was a two-fold increase in left-ventricular end-diast olic 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 dur ing hypoxia. Superimposition of pacing on hypoxic old hearts caused si x-fold increase in LVEDP; although utilization of PCr increased, it wa s still incomplete. We conclude that PCr is incompletely used to maint ain ATP level during hypoxia especially in the senescent heart, and th at the increase in LVEDP in old hearts cannot be explained solely by c hanges in indices of bioenergetics. (C) 1998 Academic Press Limited.