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Eur J Pharmacol. 1996 Feb 15;297(1-2):97-106.

Protective effects of free polyunsaturated fatty acids on arrhythmias induced by lysophosphatidylcholine or palmitoylcarnitine in neonatal rat cardiac myocytes.

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Department of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston 02114, USA.


Cultured, spontaneously beating, neonatal rat cardiac myocytes were used to examine the effects of various free fatty acids added to the medium perfusing the cells on lysophosphatidylcholine (LPC)- or acylcarnitine-induced arrhythmias. Perfusion of the cells with LPC or palmitoylcarnitine (2-10 microM) induced sustained tachyrhythmia with episodes of spasmodic contractures and fibrillation. Free PUFA (10-15 microM) including eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), alpha-linolenic acid (18:3n-3), arachidonic acid (AA, 20:4n-6) and linoleic acid (18:2n-6) were able to effectively prevent as well as terminate the LPC or acylcarnitine-induced arrhythmias. In contrast, monounsaturated oleic acid (18:1n-9) and saturated stearic acid (18:0) did not have such effects. The protective effects of the polyunsaturated fatty acids (PUFA) could be reversed by cell perfusion with delipidated bovine serum albumin. To determine the potential primary action by which the PUFA exert the antiarrhythmic effects, measurements of intracellular Ca2+ levels and the response of the cells to electrical pacing in the absence or presence of the PUFA were performed and the effects of verapamil (a L-type Ca2+ channel blocker), tetrodotoxin (a Na+ channel blocker) and Ca2+ ionophore A23187 on the cell contraction and the cytosolic Ca2+ levels were compared with that of the PUFA. Results suggest that an inhibitory effect on the electrical automaticity/excitability of the cardiac myocyte rather than a reduction in cytosolic Ca2+ underlie the protective effects of PUFA. In conclusion, free PUFAs are able to effectively protect the cardiac myocytes against the arrhythmias induced by low concentrations of lysophosphatidylcholine or palmitoylcarnitine.

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