Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids

In animal feeding studies, and probably in humans, n-3 polyunsaturated fatt y acids (PUFAs) prevent fatal ischemia-induced cardiac arrhythmias. We show ed that n-3 PUFAs also prevented such arrhythmias in surgically prepared, c onscious, exercising dogs. The mechanism of the antiarrhythmic action of n- 3 PUFAs has been studied in spontaneously contracting cultured cardiac myoc ytes of neonatal rats. Adding arrhythmogenic toxins (eg, ouabain, high Ca2, lysophosphatidylcholine, beta-adrenergic agonist, acylcarnitine, and the Ca2+ ionophore) to the myocyte perfusate caused tachycardia, contracture, a nd fibrillation of the cultured myocytes. Adding eicosapentaenoic acid (EPA : 5-15 mu mol/L) to the superfusate before adding the toxins prevented the expected tachyarrhythmias. If the arrhythmias were first induced, adding th e EPA to the superfusate terminated the arrhythmias. This antiarrhythmic ac tion occurred with dietary n-3 and n-6 PUFAs; saturated fatty acids and the monounsaturated oleic acid induced no such action. Arachidonic acid (AA; 2 0:4n-6) is anomalous because in one-third of the tests it provoked severe a rrhythmias, which were found to result from cyclooxygenase metabolites of A A. When cyclooxygenase inhibitors were added with the AA, the antiarrhythmi c 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 approximate t o 50% and prolonging the relative refractory time by approximate to 150%. T hese electrophysiologic effects result from an action of the free PUFAs to modulate sodium and calcium currents in the myocytes. The PUFAs also modula te sodium and calcium channels and have anticonvulsant activity in brain ce lls.