Fatty acid oxidation in the reperfused ischemic heart

Myocardial ATP production is dependent chiefly on the oxidative decarboxyla tion of glucose and fatty acids. The co-utilization of these and other subs trates is determined by both the amount of any given substrate supplied to the heart as well as by complex intracellular regulatory mechanisms. This r egulated balance is altered during and after ischemia. During aerobic reper fusion of ischemic myocardium, a rapid recovery of energy production is des irable for the complete recovery of muscle contractile function. It is now clear that the type of energy substrate used by the heart during reperfusio n will directly influence this contractile recovery. By increasing the rela tive proportion of glucose oxidized to that of fatty acids, the mechanical function of the reperfused heart can be improved. However, fatty acid oxida tion recovers quickly during reperfusion and dominates as a source of oxyge n consumption. These high rates of fatty acid oxidation occur at the expens e of glucose oxidation, resulting in a decreased recovery of both cardiac f unction and efficiency during reperfusion. One contributory factor to these high rates of fatty acid oxidation is a decrease in myocardial malonyl-coe nzyme A (CoA) levels. Malonyl-CoA, which is synthesized by acetyl-CoA carbo xylase, is an essential metabolic intermediary in the regulation of fatty a cid oxidation. A decrease in malonyl-CoA level results in an increase of ca rnitine palmitoyl transferase-1 mediated fatty acid uptake into the mitocho ndria. This mechanism seems important in the regulation of fatty acid oxida tion in the postischemic heart and is discussed in detail in this review, w ith reference to specific clinical scenarios of ischemia and reperfusion an d options for modulating cardiac energy metabolism.