Cardiac energy metabolism in mild and severe ischemia

Abstract

The heart must continuously produce large amounts of adenosine triphosphate (ATP) to maintain contractile function. The majority of this cardiac ATP is derived from mitochondrial oxidative phosphorylation, a process that consumes large amounts of oxygen. Ischemia results in a mismatch between oxygen demand and oxygen supply to the heart, which, in turn, results from a decrease in mitochondrial oxidative phosphorylation and an energy deficient state in the heart muscle. The magnitude of the decrease in mitochondrial oxidative phosphorylation during ischemia depends on the severity of ischemia and the degree to which oxygen supply is impaired. Glycolysis (which does not require oxygen) accelerates during ischemia in an attempt to increase ATP production. During ischemia, there are also changes in the source of energy substrate used to support residual mitochondrial oxidative phosphorylation, which includes an increase in the contribution of fatty acid oxidation, a decrease in glucose oxidation, and residual mitochondrial oxidative metabolism. Increased glycolysis accompanied by a decrease in glucose oxidation during ischemia results in an accumulation of H+ and lactate. Accumulation of these glycolytic byproducts decreases cardiac efficiency and adds to the severity of the oxygen supply-demand mismatch seen during ischemia. Therapeutic strategies that inhibit the contribution of fatty acid oxidation to residual mitochondrial oxidative metabolism will result in an increase in glucose oxidation, an improved coupling between glycolysis and glucose oxidation, a decrease in glycolytic byproduct accumulation, an increase in cardiac efficiency, and a decrease in the severity of ischemic injury. L Heart Metab. 2018;75:33-36