Previous studies have demonstrated that cardiac myocytes in the border zone of acute
myocardial infarction become markedly overloaded with neutral
lipid during the transition from reversible to irreversible injury. To examine directly the role of these changes in neutral lipid metabolism in the development of irreversible cellular injury and associated increases in tissue Ca2+ content, the authors fed rats large amounts of a
fatty acid (
erucic acid) that is poorly oxidized by the heart and that subsequently accumulates as neutral
lipid. Rats fed a high
erucic acid (C22:1) diet in the form of 20%
rapeseed oil for 3-5 days had a fourfold increase in
triglyceride (49.5 +/- 3.8 SEM mg/g wet wt versus 13.6 +/- 13, n = 4) and a 60% increase in
long-chain acyl CoA content (166.0 +/- 21.9 versus 91.5 +/- 9.0 nM/g wet wt, n = 4), compared with controls. However, there was no change in long-chain acyl
carnitine or total
phospholipid content. Histochemical studies showed accumulation of numerous lipid droplets in the myocytes, and electron microscopy revealed localization of
lipid vesicles in direct contact with mitochondria, thus mimicking the
lipid-laden cells in the border zone regions of acute
myocardial infarcts. The acute
lipidosis was reversible with either continued feeding of
erucic acid for several weeks or conversion to a normal diet. It was not associated with an increased tissue Ca2+ content, nor with cell
necrosis. However, continued
erucic acid intake for 3 months was associated with focal myocardial degeneration and loss of myocytes. These results suggest that acute increases in neutral
lipids, as found in the border zone of acute
myocardial infarction, may not be the cause of progression to irreversible damage during acute myocardial injury, but that the persistent presence of similar
lipid material over months may result in focal myocardial degeneration.