Fatty acid oxidation in the reperfused ischemic heart

Myocardial ATP production is dependent chiefly on the oxidative decarboxylation of glucose and fatty acids. The co-utilization of these and other substrates is determined by both the amount of any given substrate supplied to the heart as well as by complex intracellular regulatory mechanisms. This regulated balance is altered during and after ischemia. During aerobic reperfusion of ischemic myocardium, a rapid recovery of energy production is desirable for the complete recovery of muscle contractile function. It is now clear that the type of energy substrate used by the heart during reperfusion will directly influence this contractile recovery. By increasing the relative proportion of glucose oxidized to that of fatty acids, the mechanical function of the reperfused heart can be improved. However, fatty acid oxidation recovers quickly during reperfusion and dominates as a source of oxygen consumption. These high rates of fatty acid oxidation occur at the expense of glucose oxidation, resulting in a decreased recovery of both cardiac function and efficiency during reperfusion. One contributory factor to these high rates of fatty acid oxidation is a decrease in myocardial malonyl-coenzyme A (CoA) levels. Malonyl-CoA, which is synthesized by acetyl-CoA carboxylase, is an essential metabolic intermediary in the regulation of fatty acid oxidation. A decrease in malonyl-CoA level results in an increase of carnitine palmitoyl transferase-1 mediated fatty acid uptake into the mitochondria. This mechanism seems important in the regulation of fatty acid oxidation in the postischemic heart and is discussed in detail in this review, with reference to specific clinical scenarios of ischemia and reperfusion and options for modulating cardiac energy metabolism.