Omega‐3 Fatty Acids Do Not Protect Against Arrhythmias in Acute Nonreperfused Myocardial Infarction Despite Some Antiarrhythmic Effects

Abstract

Ventricular arrhythmias are an important cause of mortality in the acute myocardial infarction (MI). To elucidate the effect of the omega-3 polyunsaturated fatty acids (PUFAs) on ventricular arrhythmias in acute nonreperfused MI, rats were fed with normal or eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)-enriched diet for 3 weeks. Subsequently the rats were subjected to either MI induction or sham operation. ECG was recorded for 6 h after the operation and episodes of ventricular tachycardia/fibrillation (VT/VF) were identified. Six hours after MI epicardial monophasic action potentials (MAPs) were recorded, cardiomyocyte Ca(2+) handling was assessed and expression of proteins involved in Ca(2+) turnover was studied separately in non-infarcted left ventricle wall and infarct borderzone. EPA and DHA had no effect on occurrence of post-MI ventricular arrhythmias or mortality. Nevertheless, DHA but not EPA prevented Ca(2+) overload in LV cardiomiocytes and improved rate of Ca(2+) transient decay, protecting PMCA and SERCA function. Moreover, both EPA and DHA prevented MI-induced hyperphosphorylation of ryanodine receptors (RyRs) as well as dispersion of action potential duration (APD) in the left ventricular wall. In conclusion, EPA and DHA have no antiarrhythmic effect in the non-reperfused myocardial infarction in the rat, although these omega-3 PUFAs and DHA in particular exhibit several potential antiarrhythmic effects at the subcellular and tissue level, that is, prevent MI-induced abnormalities in Ca(2+) handling and APD dispersion. In this context further studies are needed to see if these potential antiarrhythmic effects could be utilized in the clinical setting. J. Cell. Biochem. 117: 2570-2582, 2016. © 2016 Wiley Periodicals, Inc.

Pigment epithelium-derived factor hinders photoreceptor cell death by reducing intracellular calcium in the degenerating retina

“…Recent reports demonstrated that PEDF–PEDF-R interactions stimulate the specific release of the omega-3 fatty acid docosahexaenoic acid (DHA) from phospholipids by the phospholipase A2 activity of PEDF-R 31 , 48 . It is worth noting that DHA can prevent Ca 2+ overload by favoring PMCA function for Ca 2+ efflux and by interfering L-type Ca 2+ channels for Ca 2+ entrance, shown both in cardiomyocytes 49 , 50 . On the one hand, we conclude that upon binding to the receptor, PEDF enhances its PLA2 activity to liberate DHA that targets PCMA favoring calcium efflux.…”

ω-3 Polyunsaturated Fatty Acid Postconditioning Protects the Isolated Perfused Rat Heart from Ischemia-Reperfusion Injury

“…In this study, ω-3 PUFA postconditioning can markedly attenuate the conditions of swellings, vacuoles, and disrupted cristae in myocardial mitochondria, suggesting that maintenance of the mitochondrial function in cardiomyocytes is implicated in the cardioprotective effects of ω-3 PUFA postconditioning. Recently, Mączewski et al [25] reported that DHA supplementation prevented calcium overload in rat cardiomyocytes. Meanwhile, Madingou et al [26] demonstrated that DHA supplementation conferred resistance to MPTP opening in a murine model of myocardial infarction.…”

Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs

“…These limitations should be taken into consideration when interpreting the findings obtained in the same canine SCD model [ 132 , 133 ]. Another study demonstrated that supplementation of rats with omega-3 PUFAs for 3 weeks did not protect against AMI related VT/VF, although, at the cellular level they prevented calcium overload [ 134 ]. All limitations of the study should be taken into consideration when analyzing the possible factors implicated in the lack of anti-arrhythmic effects.…”