Fatty acid metabolism in the reperfused ischemic heart

Abstract

Abstract Elevated serum levels of fatty acids can be seen in most clinically relevant situations of myocardial ischemia. During an episode of mild to moderate ischemia these high levels of fatty acid have been shown to contribute to contractile dysfunction. Recent evidence suggests that high levels of fatty acids also depress the recovery of contractile function following a transient episode of severe ischemia. The mechanisms by which fatty acid are detrimental during reperfusion of severely ischemic hearts appears to differ from the mechanism by which fatty acids enhance injury during ischemia itself. Evidence from our laboratory suggests that a marked depression of glucose oxidation during reperfusion may be primarily responsible for the detrimental effects of high levels of fatty acids. This is supported by the observation that interventions which overcome fatty acid inhibition of glucose oxidation will significantly improve post-ischemic functional recovery. The exact reason(s) why stimulating glucose oxidation during reperfusion is beneficial has yet to be determined. As will be discussed in this paper, we speculate that stimulation of glucose oxidation improves the coupling between glycolysis and glucose oxidation in the immediate reperfusion period. By doing so, a reduction in H+ production from glucose metabolism will occur during the actual reperfusion period. This will result in a lessening of the myocardial H+ load during the critical period in which the heart is recovering from the acidosis that has occurred during the actual ischemic episode. Inhibition of glucose oxidation by fatty acids may not contribute to injury following a period of mild to moderate ischemia, since the decrease in myocardial pH during ischemia is less dramatic. As a result, the heart is not overwhelmed with a high intracellular H+ load during reperfusion.