HYPERPERFUSION AND CARDIOPLEGIA EFFECTS ON MYOCARDIAL HIGH-ENERGY PHOSPHATE DISTRIBUTION AND ENERGY-EXPENDITURE

This study examines the hypothesis that high-energy phosphate (HEP) co mpound levels in unstimulated in vivo myocardium are defined by 1) the level of perfusion and 2) nonperfusion-dependent metabolic characteri stics. This hypothesis was tested by determining 1) the effects of pha rmacological hyperperfusion of functioning myocardium on transmural HE P compound distribution, contractile function, and myocardial oxygen c onsumption rate (MVO(2)) as well as 2) the effects of KC1 cardioplegia on transmural myocardial HEP compound distribution. Creatine phosphat e (CP) and ATP were measured across the anterior left ventricular wall using spatially localized P-31-nuclear magnetic resonance (NMR). At b aseline, the CP-to-ATP (CP/ATP) ratio was significantly lower in the s ubendocardium than in the subepicardium. This transmural HEP gradient was abolished by hyperperfusion without significant effects on contrac tile function or MVO(2). Similarly, KC1 arrest significantly increased CP and CP/ATP in all myocardial layers, and the transmural gradient o f CP/ATP was abolished again. These studies indicate that in present e xperimental model 1) myocardial performance is not constrained by inad equate perfusion in any myocardial layer although modest oxygen limita tion affects the kinetics of oxidative phosphorylation in the inner my ocardial layers and 2) in all myocardial layers, submaximal activation of intermediary metabolism and oxidative phosphorylation reactions re sults in lower steady-state CP and higher ADP levels relative to their respective values when energy expenditure is markedly reduced by KC1 arrest.