The electrophysiological basis for the antiarrhythmic actions of polyunsaturated fatty acids

Aims To determine whether n-3 polyunsaturated fatty acids (PUFAs) have cardiac antiarrhythmic effects and, if so, to determine the basis(es) for such an effect. Methods and results First, tests were made of the ability of administering n-3 PUFAs to a reliable dog model to prevent ischaemia-induced sudden cardiac death. Infusion of an emulsion of fish oil free fatty acids just prior to coronary artery obstruction prevented ventricular fibrilation (VF) ( \(P{<}0{\cdot}005\) ) in exercising, unanaesthetized dogs. Similar results were obtained with pure n-3 free docosahexaenoic, eicosapentaenoic or alpha-linolinic acids. PUFAs prevented induced fibrillation of cultured neonatal rat cardiomyocytes for all cardiotoxins tested. After fibrillation was induced, the arrhythmias were terminated by the PUFAs. The electrophysiological effects of low micromolar concentrations of PUFAs are to increase the depolarizing current required to elicit an action potential by about 50% and prolong the refractory period by about threefold. These effects result because the PUFAs modulate the conductance of ion channels, primarily of Na⁺ and Ca²⁺, in cardiomyocytes from neonatal and adult rats and the human myocardial Na⁺ channel with the alpha-subunit and the alpha+beta-subunits transiently expressed in HEK293t cells using whole cell patch-clamp. Conclusions These dietary PUFAs are shown to be potent, safe antiarrhythmic agents. More clinical trials, such as the GISSI-Prevenzione, are needed to extend these findings to humans. Potential, very large public health benefits may accrue from this new understanding.