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 m M ), linoleate (1 to 1.75 m M ), octanoate (0.5 to 1.75 m M ) and pent-4-enoic acid (1 to 5 m M ) on mechanical performance under oxygenated, hypoxic and anoxic conditions. The buffer solution contained 0.3 m M albumin. Free fatty acids (FFA) (1.0 to 1.75 m M ) did not alter mechanical performance under oxygenated conditions. During hypoxia or anoxia, FFA (0.5 to 1.75 m M ) 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.