MYOCARDIAL-CELL DAMAGE BY FATTY-ACID ETHYL-ESTERS

Fatty acid ethyl ester (FAEE), a myocardial metabolite of ethanol, cau ses mitochondrial dysfunction in vitro in rabbits. We investigated the effect of these esters on rat heart mitochondria in vitro and in vivo . In vitro studies were conducted to investigate the binding of ethyl oleate (FAEE) to mitochondria and their capacity to hydrolyze these FA EE. In vivo effects of ethyl esters were studied by the direct transfe r of [H-3]oleate into the myocardium. Mitochondria were prepared from the myocardium of injected rats, and the amount of [H-3]oleate bound t o them was determined. In another in vivo study, 50 mu l of 50 mu M co ld oleic acid ethyl ester was injected into the rat myocardium and the histopathological changes induced by oleic acid ethyl ester were exam ined by light microscopy. Our results show that fatty acid ethyl ester can bind to myocardial mitochondria in vitro as well as in vivo and t he mitochondria can hydrolyze FAEE to fatty acid, which is a known unc oupler of oxidative phosphorylation. Of the total ethyl [H-3] oleate i njected, 8 mu M [H-3]oleate and 1 mu M ethyl [H-3]oleate was bound to the mitochondria. Significant myocardial cell damage was first observe d on day 4 and markedly increased on day 30 after ethyl ester injectio n, with cells showing gross deformation and enlargement. However, no s ignificant histopathological changes were observed in the myocardial t issue on day 2 after injection. Our results suggest that the FAEE may damage the myocardial cells as well as the mitochondria and may provid e a metabolic link between ethanol abuse and myocardial dysfunction.