Metabolic therapy for ischemic heart disease: The rationale for inhibition of fatty acid oxidation

In summary, myocardial metabolism is dramatically altered by myocardial ischemia; the rates of 278 Stanley and Sabbah oxygen consumption and ATP production are reduced, leading to a reduction in ATP content, high rates of glycolysis and lactate accumulation, and decreased intracellular pH. Despite a high rate of lactate production the ischemic heart continues to derive most of its energy (60-80%) from the oxidation of fatty acids. During ischemia the oxidation of pyruvate is inhibited by the relatively high rate of fatty acid oxidation, resulting in accelerated lactate production, intracellular acidosis, and a decrease in ATP concentration. Ischemiainduced disruption in cardiac metabolism can be minimized by metabolic agents that partially reduce fatty acid oxidation, such as the 3-KAT inhibitor trimetazidine, resulting in clinical benefit to the ischemic patient. © Springer Science + Business Media, LLC 2006.