Myocardial Substrate Metabolism in the Normal and Failing Heart
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Abstract
The alterations in myocardial energy substrate metabolism that occur in heart failure, and the causes and consequences of these abnormalities, are poorly understood. There is evidence to suggest that impaired substrate metabolism contributes to contractile dysfunction and to the progressive left ventricular remodeling that are characteristic of the heart failure state. The general concept that has recently emerged is that myocardial substrate selection is relatively normal during the early stages of heart failure; however, in the advanced stages there is a downregulation in fatty acid oxidation, increased glycolysis and glucose oxidation, reduced respiratory chain activity, and an impaired reserve for mitochondrial oxidative flux. This review discusses 1) the metabolic changes that occur in chronic heart failure, with emphasis on the mechanisms that regulate the changes in the expression of metabolic genes and the function of metabolic pathways; 2) the consequences of these metabolic changes on cardiac function; 3) the role of changes in myocardial substrate metabolism on ventricular remodeling and disease progression; and 4) the therapeutic potential of acute and long-term manipulation of cardiac substrate metabolism in heart failure.
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The record
- Venue
- Physiological Reviews
- Topic
- Fuel Cells and Related Materials
- Field
- Engineering
- Canadian institutions
- University of Alberta
- Funders
- National Heart, Lung, and Blood InstituteServierFondation pour la Recherche MédicaleSchool of Medicine, Case Western Reserve UniversityCase Western Reserve University
- Keywords
- Heart failureInternal medicineBeta oxidationMetabolismDownregulation and upregulationOxidative phosphorylationGlycolysisMitochondrionFatty acid metabolismVentricular remodelingMedicineEndocrinologyMetabolic pathwayCardiac function curveCardiologyBiologyBiochemistry
- Has abstract in OpenAlex
- yes