Skeletal muscle metabolism in heart failure in rats.
31P nuclear magnetic resonance (NMR) was used to examine the metabolism of skeletal muscle in rats 6-8 wk after myocardial infarction (MI). These in vivo measurements were supplemented by measurement of creatine, phosphocreatine (PCr), and ATP in freeze-clamped muscle using high-performance liquid chromatography (HPLC) and assays of key muscle enzymes to better define the muscle abnormality observed in heart failure. Resting PCr/(PCr + Pi) and pH were similar in MI rats and controls. Rats with MI had lower pH and PCr/(PCr + Pi) than controls during sciatic nerve stimulation at 1 and 2 Hz. These changes were more severe in rats with large (greater than or equal to 46%) infarcts, and changes in pH and PCr/(PCr + Pi) were correlated with infarct size. Free [ADP] in vivo was estimated from the NMR and HPLC measurements. [ADP] was increased in rats with large infarcts during nerve stimulation, implying a defect in oxidative metabolism. Citrate synthase, a mitochondrial enzyme, was reduced in rats with large MI. Citrate synthase levels were correlated with changes in PCr/(PCr + Pi) at 2 Hz. The NMR changes in skeletal muscle can be explained by reduced oxidative capacity of skeletal muscle, and this proposition is supported by the demonstration of reduced citrate synthase levels in skeletal muscle of rats with large infarcts.
Arnolda
L
L
Medical Research Council Biochemical and Clinical Magnetic Resonance Unit, Oxford University, United Kingdom.
Brosnan
J
J
Rajagopalan
B
B
Radda
G K
GK
D000704:Analysis of Variance; D000818:Animals; D002303:Cardiac Output, Low / Q000175:diagnosis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004558:Electric Stimulation; D004734:Energy Metabolism; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D009119:Muscle Contraction; D009132:Muscles / Q000201:enzymology / Q000378:metabolism*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000378:metabolism; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology
D010710:Phosphates; D002950:Citrate (si)-Synthase