Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes.

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Abstract
Isolated neonatal cardiac myocytes have been utilized as a model for the study of cardiac arrhythmogenic factors. The myocytes respond to the toxic effects of a potent cardiac glycoside, ouabain at 0.1 mM, by an increase in their spontaneous beating rate and a reduction in amplitude of contractions resulting within minutes in a lethal state of contracture. Incubating the isolated myocytes for 3-5 days in culture medium enriched with 5 .mu.M arachidonic acid [20:4 (n-6)] had no effect on the development of lethal contracture after subsequent exposure to 0.1 mM ouabain. By contrast, incubating the myocytes for 3-5 days with 5 .mu.M eicosapentaenoic acid [20:5 (n-3)] completely prevented the toxic effects of ouabain at 0.1 mM. There were no measurable differences in the degree to which ouabain inhibited Na,K-ATPase activity by comparing the control with the arachidonic acid- or the eicosapentaenoic acid-enriched myocytes. No differences in bumetanide-inhibitable 86Rb flux were observed between the three preparations. However, measurements with fura-2 of cytosolic free calcium levels indicated that control and arachidonic acid-enriched myocytes developed toxic cytosolic calcium concentrations of 845 .+-. 29 and 757 .+-. 64 nM, respectively, on exposure to 0.1 mM ouabain, whereas in eicosapentaenoic acid-enriched myocytes, physiologic calcium levels (214 .+-. 29 nM) were preserved. Incubating the myocytes with eicosapentaenoic acid (5 .mu.M) for 3-5 days resulted in a small reduction of arachidonic acid and a small but significant increase of eicosapentaenoic acid in membrane phospholipids of the myocytes.

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