Mączewski Michał, Duda Monika, Marciszek Mariusz, Kołodziejczyk Joanna, Dobrzyń Paweł, Dobrzyń Agnieszka, Mackiewicz Urszula
Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland.
Laboratory of Molecular and Medical Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
J Cell Biochem. 2016 Nov;117(11):2570-82. doi: 10.1002/jcb.25550. Epub 2016 Apr 6.
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.
室性心律失常是急性心肌梗死（MI）患者死亡的重要原因。为了阐明ω-3多不饱和脂肪酸（PUFAs）对急性非再灌注性心肌梗死室性心律失常的影响，将大鼠分别喂食正常饮食或富含二十碳五烯酸（EPA）或二十二碳六烯酸（DHA）的饮食3周。随后，对大鼠进行心肌梗死诱导或假手术。术后记录心电图6小时，确定室性心动过速/心室颤动（VT/VF）发作情况。心肌梗死后6小时记录心外膜单相动作电位（MAPs），评估心肌细胞Ca(2+)处理情况，并分别在非梗死左心室壁和梗死边缘区研究参与Ca(2+)周转的蛋白质表达。EPA和DHA对心肌梗死后室性心律失常的发生或死亡率没有影响。然而，DHA而非EPA可防止左心室心肌细胞Ca(2+)超载，并提高Ca(2+)瞬变衰减率，并保护质膜钙ATP酶（PMCA）和肌浆网钙ATP酶（SERCA）功能。此外，EPA和DHA均可防止心肌梗死诱导的兰尼碱受体（RyRs）过度磷酸化以及左心室壁动作电位时程（APD）离散。总之，EPA和DHA对大鼠非再灌注性心肌梗死没有抗心律失常作用，尽管这些ω-3多不饱和脂肪酸，尤其是DHA，在亚细胞和组织水平上表现出几种潜在的抗心律失常作用，即防止心肌梗死诱导的Ca(2+)处理异常和APD离散。在这种情况下，需要进一步研究看看这些潜在的抗心律失常作用是否可用于临床。《细胞生物化学杂志》1 : 2570 - 2582, 2016。© 2016威利期刊公司
