title: Heart failure: a model of cardiac and skeletal muscle energetic failure.
abstract: Chronic heart failure (CHF), the new epidemic in cardiology, is characterized by energetic failure of both cardiac and skeletal muscles. The failing heart wastes energy due to anatomical changes that include cavity enlargement, altered geometry, tachycardia, mitral insufficiency and abnormal loading, while skeletal muscle undergoes atrophy. Cardiac and skeletal muscles also have altered high-energy phosphate production and handling in CHF. Nevertheless, there are differences in the phenotype of myocardial and skeletal muscle myopathy in CHF: cardiomyocytes have a lower mitochondrial oxidative capacity, abnormal substrate utilisation and intracellular signalling but a maintained oxidative profile; in skeletal muscle, by contrast, mitochondrial failure is less clear, and there is altered microvascular reactivity, fibre type shifts and abnormalities in the enzymatic systems involved in energy distribution. Underlying these phenotypic abnormalities are changes in gene regulation in both cardiac and skeletal muscle cells. Here, we review the latest advances in cardiac and skeletal muscle energetic research and argue that energetic failure could be taken as a unifying mechanism leading to contractile failure, ultimately resulting in skeletal muscle energetic failure, exertional fatigue and death.
authors.affiliation: Département de Physiologie, CHRU, EA3072, F-67091 Strasbourg, France. bertrand.mettauer@ch-colmar.rss.fr
authors.forename: B
authors.initials: B
authors.lastname: Mettauer
authors.forename: J
authors.initials: J
authors.lastname: Zoll
authors.forename: A
authors.initials: A
authors.lastname: Garnier
authors.forename: R
authors.initials: R
authors.lastname: Ventura-Clapier
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004734:Energy Metabolism / Q000502:physiology*; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D032342:Muscle Cells / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*