FUNCTION AND BIOENERGETICS IN ISOLATED-PERFUSED TRAINED RAT HEARTS

To evaluate the resistance of physiologically hypertrophied hearts to hypoxic insult, we quantified the development of functional deficits d uring hypoxia and reoxygenation in hypertrophied hearts from swim-trai ned female rats and we correlated this with assessment of high-energy phosphate (HEP) metabolites from simultaneous P-31 nuclear magnetic re sonance (NMR) measurements. Furthermore, in vive enzymatic studies wer e carried out with saturation transfer NMR under well-oxygenated perfu sion conditions for both beating and KCl-arrested hearts. Finally, in vitro enzymatic assays were performed. During hypoxia, the trained hea rts exhibited improved systolic and diastolic function compared with h earts from sedentary animals. After 16 min of hypoxia, left ventricula r (LV) developed pressure fell to 9% of baseline in control hearts but to only 21% of baseline in trained hearts (P < 0.01). LV diastolic fu nction was also improved by training, increasing during hypoxia from a baseline of 10 to 71.0 +/- 3.3 mmHg in control hearts and to 55.3 +/- 4.8 mmHg in trained hearts (P < 0.05). Trained hearts also showed mor e rapid and complete recovery of function during reoxygenation and gre ater coronary flow per gram of heart throughout the entire protocol. F unctional differences were not accompanied by differences in HEP at ba seline; moreover, ATP and phosphocreatine (PCr) loss during hypoxia wa s similar between control and trained hearts, as was the recovery of P Cr during reoxygenation. Saturation transfer experiments showed an inc rease in the forward creatine kinase (CrK) rate constant in trained he arts of 18% while beating, whereas in vitro enzymatic analysis reveale d a 16% increase in the ratio of mitochondrial CrK to citrate synthase activity in LV tissue. Thus the relative preservation of function in hearts from trained rats could not be accounted for by overall HEP lev els but may reflect adaptations in the CrK system.