Effects of free fatty acid and enzyme release in experimental glucose on myocardial infarction

Abstract

IN physiological concentrations, circulating long chain free fatty acids (FFA) can inhibit the myocardial oxidation of glucose and are the preferred fuel of the heart in the fasted state^1,2. In sufficiently high concentrations, fatty acids as the only fuel can have toxic effects on the normal perfused rat heart³. The mechanisms involved in fatty acid toxicity may include the intracellular accumulation of products of fatty acid metabolism such as acyl CoA (ref. 4), which inhibits the transfer of ATP from sites of synthesis in the mitochondria to sites of utilisation in the cytoplasm. Thus, enhanced rates of FFA metabolism could be expected to aggravate myocardial infarction, in which there is a loss of ATP in the poorly perfused tissue predominantly supplied by the occluded artery⁵. As an intracellular ATP deficiency is postulated to be a factor promoting release of enzymes⁶, increased provision of FFA to the heart should accelerate enzyme release from infarcting heart tissue. Conversely, if the rate of accumulation of FFA breakdown products were decreased by the additional provision of glucose or glucose plus insulin to promote intracellular esterification of FFA, then the rate of enzyme release should be decreased. Increased provision of glucose could also result in increased production of anaerobic ATP which could be of importance in promoting the survival of the oxygen-limited myocardium⁷.