Pyruvate: metabolic protector of cardiac performance.
Pyruvate, a metabolic product of glycolysis and an oxidizable fuel in myocardium, increases cardiac mechanical performance and energy reserves, especially when supplied at supraphysiological concentrations. The inotropic effects of pyruvate are most impressive in hearts that have been reversibly injured (stunned) by ischemia/reperfusion stress. Glucose appears to be an essential co-substrate for pyruvate's salutary effects in stunned hearts, but other fuels including lactate, acetate, fatty acids, and ketone bodies produce little or no improvement in postischemic function over glucose alone. In contrast to pharmacological inotropism by catecholamines, metabolic inotropism by pyruvate increases cardiac energy reserves and bolsters the endogenous glutathione antioxidant system. Pyruvate enhancement of cardiac function may result from one or more of the following mechanisms: increased cytosolic ATP phosphorylation potential and Gibbs free energy of ATP hydrolysis, enhanced sarcoplasmic reticular calcium ion uptake and release, decreased cytosolic inorganic phosphate concentration, oxyradical scavenging via direct neutralization of peroxides and/or enhancement of the intracellular glutathione/NADPH antioxidant system, and/or closure of mitochondrial permeability transition pores. This review aims to summarize evidence for each of these mechanisms and to consider the potential utility of pyruvate as a therapeutic intervention for clinical management of cardiac insufficiency.
Mallet
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RT
Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth 76107-2699, USA. malletr@hsc.unt.edu
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism; D005544:Forecasting; D006321:Heart / Q000502:physiology*; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum
D011773:Pyruvates; D002118:Calcium