Energy use by contractile and noncontractile processes in skeletal muscle estimated by 31P-NMR.

The goal of this study was to separately determine ATP use by contractile and noncontractile processes in stimulated skeletal muscle. ATP use by tetanically stimulated bullfrog semitendinosus muscle was monitored at room temperature with in vivo 31P-nuclear magnetic resonance. Oxidative phosphorylation was inhibited by cyanide, and ATP use could therefore be calculated by accounting for ATP derived from the creatine kinase (CK) reaction (measured from decreases in phosphocreatine) and from glycolysis (estimated from decreases of intracellular pH). In unfatigued muscles stimulated at optimal length for force production, total ATP utilization (representing both contractile and noncontractile processes) was 2.5 +/- 0.09 (SE) mM/s (n = 6; 53% ATP from glycolysis, 47% from CK). In separate experiments, cross-bridge interactions between actin and myosin filaments were eliminated by increasing sarcomere length; therefore, with stimulation, residual ATP use reflected only noncontractile processes. In stimulated stretched muscles, ATP utilization was reduced compared with unstretched muscles to 1.07 +/- 0.08 mM/s (61% ATP from glycolysis, 39% from CK). These findings suggest that, during contraction near optimum length, a large proportion (approximately 43%) of ATP is used by noncontractile processes, with more ATP derived from glycolysis than from CK.

Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo.

BACKGROUND: The functional impairment of persistently ischemic, or "hibernating," myocardium may serve to maintain myocardial cell viability through a reduction of energy requirements. Although previous studies have, in a variety of experimental models, independently shown variable responses in lactate metabolism and intracellular phosphates during prolonged ischemia, the responses of these metabolites under identical flow conditions have not been adequately described. METHODS AND RESULTS: To examine the responses of high-energy phosphates and lactate metabolism to prolonged ischemia induced by partial coronary artery stenosis, 12 open-chest pigs were studied using 31P nuclear magnetic resonance spectroscopy. Concurrent measurements of blood flow, segment shortening, high-energy phosphates, and lactate release (in nine animals) were made during 2 hours of regional ischemia. Subendocardial blood flow and segment shortening were persistently depressed during ischemia, with parallel reductions in ATP, phosphocreatine (PCr), and the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Pi was persistently elevated during the ischemic period. In contrast, lactate release increased significantly from 0.23 +/- 0.04 to 1.34 +/- 0.28 mumol/ml after 15 minutes of ischemia (p less than 0.05) but then decreased to 0.73 +/- 0.17 mumol/ml at 2 hours (p less than 0.05 versus 15 minutes, p = NS versus control). Similarly, pH increased significantly from a nadir of 6.82 +/- 0.07 at 30 minutes of ischemia to 6.98 +/- 0.05 at 2 hours. CONCLUSIONS: Changes in high-energy phosphates parallel changes in blood flow and function during prolonged ischemia, whereas there is a partial amelioration in lactate production and acidosis. These data support the concept that reduction of myocardial energy requirements during prolonged flow reduction results in signs of reduced ischemia.