Relation among regional O2 consumption, high-energy phosphates, and substrate uptake in porcine right ventricle

Abstract

Changes in phosphate metabolites may play a role in the regulation of myocardial oxidative phosphorylation in vivo. We tested the hypothesis that changes in phosphate metabolites with increased myocardial oxygen consumption (MVO2) depend on the mechanism by which MVO2 is increased. In 17 open-chest pigs, regional MVO2 of the right ventricular (RV) free wall was increased from control by isoproterenol infusion (Iso) and by pulmonary artery constriction (PAC). The phosphocreatine-to-ATP ratio (PCr/ATP), which is inversely related to free ADP concentration ([ADP]), was determined by 31P-nuclear magnetic resonance (NMR) spectroscopy. Regional MVO2 and lactate, glucose, and free fatty acid (FFA) uptake were determined in the myocardium directly beneath the NMR coil. Iso and PAC increased MVO2 nearly equally, to approximately twice control, but produced directionally opposite changes in PCr/ATP: a significant decrease with PAC (control 1.52 +/- 0.06, PAC 1.35 +/- 0.06, means +/- SE) but a significant increase with Iso (to 1.72 +/- 0.07). Thus increased [ADP] may have stimulated oxidative phosphorylation during PAC but could not have done so during Iso. With Iso, uptake of FFA was more than three times that with PAC, and the sum of the oxygen extraction ratios for lactate, glucose, and FFA was more than double that with PAC. Enhanced substrate uptake during Iso may have increased mitochondrial NADH, which in turn may have provided an alternative stimulus to the rate of oxidative phosphorylation. These results support multifactorial control of RV oxidative phosphorylation in vivo.