Depression of Myocardial Contractility in Rats by Free Fatty Acids during Hypoxia

Abstract

Rat papillary muscles were used to study the influence of glucose (5 HIM), linoleate (1 to 1.75 mMJ, octanoate (0.5 to 1.75 HIM) and pent-4-enoic acid (1 to 5 DIM) on mechanical performance under oxygenated, hypoxic and anoxic conditions. The buffer solution contained 0.3 DIM albumin. Free fatty acids (FFA) (1.0 to 1.75 DIM) did not alter mechanical performance under oxygenated conditions. During hypoxia or anoxia, FFA (0.5 to 1.75 HIM) depressed contractility and increased resting force; glucose improved mechanical performance and modified the depressant effects of FFA. The depressant effect of the nonmetabolized FFA, pentenoic acid, was similar to that of other FFA. This suggests that the effect was mediated directly by FFA or acyl CoA derivatives rather than their metabolic products, and that it might be due to a detergent effect or calcium binding by FFA present in excess of intracellular FFA binding capacity at low pH. Force development during anoxia could be augmented by calcium, implying that the reduced ability of the myofilaments to contract could not be attributed entirely to a reduction of high energy stores. ADDITIONAL KEY WORDSlinoleate octanoate pent-4-enoic acid calcium binding detergent action of free fatty acids optimal oxygen requirement of rat myocardium paired stimulation• It has been demonstrated that glucose improves the mechanical performance and prolongs the survival of anoxic hearts (1-4), but the possible influence of free fatty acids (FFA) under conditions of oxygen deprivation has received little attention. High concentrations of FFA have been shown to increase myocardial oxygen consumption (MV02) in aerobically perfused rat hearts (5) and to cause arrhythmias in dogs with experimentally induced infarction (6). Furthermore, high serum levels of FFA have been correlatedFrom the Cardiovascular Division, Peter Bent

Effect of Free Fatty Acids on Myocardial Function and Oxygen Consumption in Intact Dogs

“…Mechanical factors, however, can be ruled out as responsible for the elevated MYO2, as systolic and enddiastolic LVP, dP/dt, CO, and HR remained unchanged during raised plasma-FFA. These results are in accordance with Henderson, Most, Parmley, Gorlin, and Sonnenblick (12) who found that FFA did not alter developed force in well-oxygenated rat papillary muscle.…”

Effect of Inhibition of Lipolysis on Infarct Size After Experimental Coronary Artery Occlusion

“…Marked depression of myocardial contractility has been observed in oxygen-limited hearts receiving high concentrations of FFA (11,12). This has been attributed to increased oxygen demand (12), suggesting that FFA in high concentrations contribute to the myocardial cell injury.…”

Effect of inhibition of lipolysis on myocardial oxygen consumption in the presence of isoproterenol

“…Although the beneficial effect of glucose is known in isolated hearts during oxygen deprivation and subsequent recovery (19)(20)(21)(22), clinical trials with glucose, potassium, and insulin in patients with acute myocardial infarction have yielded conflicting results (23)(24)(25). However, as pointed out by Owen, Thomas, and Opie (26), and by Henderson, Most, Parmley, Gorlin, and Sonnenblick (27), this treatment has been directed rather towards replacing intracellular potassium than depressing myocardial uptake of FFA through high plasma glucose concentrations. As a result, plasma FFA and myocardial uptake of FFA were not measured in these studies.…”