Myocardial tissue free fatty acids

Myocardial ischaemia, whether produced by coronary artery ligation or by hypoxic low-flow perfusion of the isolated rat heart, has been shown to be associated with a significant depression in mitochondrial function, as well as an increase in tissue free fatty acid (FFA) levels. Although the effects of FFA on mitochondrial oxidative phosphorylation function in vitro are well established, it has not yet been shown that increased tissue FFA levels are causing the depression in mitochondrial function in ischaemia. Using the isolated perfused rat heart, several experiments were performed to gain more information regarding (i) the validity of the Dole FFA extraction technique; (ii) controlling factors; (iii) the relationship between tissue FFA and mitochondrial function and (iv) sources of tissue FFA in ischaemia. Significant elevation of tissue FFA was achieved by perfusion with (i) substrate-free Ringer and (ii) phosphatidylcholine. Elevation of tissue FFA obtained by perfusing with long-chain fatty acids was due to extracellular accumulation. Reduction of tissue FFA levels was observed by perfusing with (i) albumin, (ii) glucose, insulin and propranolol. Our results also suggest that lysosomal involvement could cause the increase in tissue FFA levels in myocardial ischaemia.