Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids.
In animal feeding studies, and probably in humans, n-3 polyunsaturated fatty acids (PUFAs) prevent fatal ischemia-induced cardiac arrhythmias. We showed that n-3 PUFAs also prevented such arrhythmias in surgically prepared, conscious, exercising dogs. The mechanism of the antiarrhythmic action of n-3 PUFAs has been studied in spontaneously contracting cultured cardiac myocytes of neonatal rats. Adding arrhythmogenic toxins (eg, ouabain, high Ca(2+), lysophosphatidylcholine, beta-adrenergic agonist, acylcarnitine, and the Ca(2+) ionophore) to the myocyte perfusate caused tachycardia, contracture, and fibrillation of the cultured myocytes. Adding eicosapentaenoic acid (EPA: 5-15 micromol/L) to the superfusate before adding the toxins prevented the expected tachyarrhythmias. If the arrhythmias were first induced, adding the EPA to the superfusate terminated the arrhythmias. This antiarrhythmic action occurred with dietary n-3 and n-6 PUFAs; saturated fatty acids and the monounsaturated oleic acid induced no such action. Arachidonic acid (AA; 20:4n-6) is anomalous because in one-third of the tests it provoked severe arrhythmias, which were found to result from cyclooxygenase metabolites of AA. When cyclooxygenase inhibitors were added with the AA, the antiarrhythmic effect was like those of EPA and DHA. The action of the n-3 and n-6 PUFAs is to stabilize electrically every myocyte in the heart by increasing the electrical stimulus required to elicit an action potential by approximately 50% and prolonging the relative refractory time by approximately 150%. These electrophysiologic effects result from an action of the free PUFAs to modulate sodium and calcium currents in the myocytes. The PUFAs also modulate sodium and calcium channels and have anticonvulsant activity in brain cells.
Kang
J X
JX
Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA.
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D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004594:Electrophysiology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology / Q000502:physiology*; D005395:Fish Oils / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007473:Ion Channels / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010805:Physical Conditioning, Animal; D051381:Rats; D014693:Ventricular Fibrillation / Q000401:mortality / Q000517:prevention & control*
D002316:Cardiotonic Agents; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D007473:Ion Channels; D010042:Ouabain; D015118:Eicosapentaenoic Acid; D002118:Calcium