Perturbations in myocardial energy metabolism in the ischemic heart

As an organ that must continuously pump oxygenated blood throughout the body, the heart has an enormous metabolic demand, which is primarily met via oxidative metabolism of fatty acids and carbohydrates. Because of its high metabolic demand, during times of reduced oxygen supply such as ischemia, the heart becomes highly susceptible to injury, and if flow is not re-established, myocardial tissue is lost and can result in death (myocardial infarction). Of interest, both myocardial ischemia and reperfusion are associated with a number of perturbations in energy metabolism that contribute to the pathology of ischemic heart disease. This includes marked elevations in glycolysis to counteract the reduction in oxidative metabolism, whereas fatty acids predominate as the primary fuel source for residual oxidative metabolism. During the early stages of cardiac recovery after successful reperfusion of the ischemic heart, fatty acid oxidation rates also rapidly recover at the expense of low glucose oxidation rates. These metabolic perturbations increase myocardial acidosis due to glycolysis being uncoupled from glucose oxidation, which impairs cardiac efficiency. As such, therapeutic approaches to stimulate glucose oxidation or inhibit fatty acid oxidation have the potential to correct dysregulated myocardial energy metabolism during ischemia and reperfusion, which improves cardiac efficiency and may lead to improved clinical outcomes in people with ischemic heart disease. L