Ventricular arrhythmias are a major source of early mortality in acute myocardial infarction (MI) and remain a major therapeutic challenge. Thus we investigated effects of ivabradine, a presumably specific bradycardic agent versus metoprolol, a β-blocker, at doses offering the same heart rate (HR) reduction, on ventricular arrhythmias in the acute non-reperfused MI in the rat. Immediately after MI induction a single dose of ivabradine/ metoprolol was given. ECG was continuously recorded and ventricular arrhythmias were analyzed. After 6 h epicardial monophasic action potentials (MAPs) were recorded and cardiomyocyte Ca2+ handling was assessed. Both ivabradine and metoprolol reduced HR by 17% and arrhythmic mortality (14% and 19%, respectively, versus 33% in MI, p < 0.05) and ventricular arrhythmias in post-MI rats. Both drugs reduced QTc prolongation and decreased sensitivity of ryanodine receptors in isolated cardiomyocytes, but otherwise had no effect on Ca2+ handling, velocity of conduction or repolarization. We did not find any effects of potential IKr inhibition by ivabradine in this setting. Thus Ivabradine is an equally effective antiarrhythmic agent as metoprolol in early MI in the rat. It could be potentially tested as an alternative antiarrhythmic agent in acute MI when β-blockers are contraindicated.
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.
The effect of omega-3 polyunsaturated fatty acids enriched diet on the contractile function, structure, Ca2+ handling and electrophysiology in the rat heart** Wpływ diety wzbogaconej w wielonienasycone kwasy tłuszczowe omega-3 na funkcję skurczową i morfologię lewej komory oraz na wewnątrzkomórkowy obieg Ca2+ i elektrofizjologię w sercu szczura Department of Clinical Physiology, Medical Center of Postgraduate Education, Warszawa Head of Department: Michał Mączewski, MD, PhD S u m m a r y Introduction. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are essential fatty acids that cannot be synthesized by mammals and must be delivered with food. Epidemiological observations suggest that supplementation of ω-3 PUFA reduces cardiovascular mortality, although results of clinical trials and animal studies are highly variable and inconsistent.Aim. The aim of the study was to examine cardiovascular effects of ω-3 PUFA supplementation in healthy rats. Eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), the two most commonly used ω-3 PUFAs, were used.Material and methods. Rats were fed with normal chow or EPA-or DHA-enriched diet for 4 weeks. Epicardial monophasic action potentials (MAPs) were recorded, cardiomyocyte Ca 2+ handling was assessed and eachocardiographic imaging was performed before and after 4 weeks of feeding.Results. Neither EPA nor DHA affected left ventricular (LV) ejection fraction, wall thickness or diameters, indicating that 4 weeks of feeding had no effect on LV structure and function. While EPA enriched diet had no impact on intracellular Ca 2+ handling, DHA-rich diet significantly increased amplitude of Ca 2+ transient and SR Ca 2+ content. Neither EPA nor DHA affected action potential duration, however EPA mildly increased action potential amplitude.Conclusions. This indicates that ω-3 PUFAs are safe for the cardiovascular system, but the above mentioned cellular effects may be considered arrhythmogenic under specific conditions. S t r e s z c z e n i e Wstęp. Wielonienasycone kwasy omega-3 (ω-3 WNKT) należą do grupy tzw. niezbędnych kwasów tłuszczowych, których organizm ssaków nie może syntetyzować de novo i muszą być one dostarczane z pokarmem. Badania epidemiologiczne sugerują, że suplementacja ω-3 WNKT zmniejsza śmiertelność z przyczyn sercowo-naczyniowych. Jednakże przeprowadzone dotychczas badania kliniczne i podstawowe dostarczyły różnorodnych i często sprzecznych wyników.Cel pracy. Celem tej pracy jest zbadanie wpływu suplementacji dwóch głównych przedstawicieli ω-3 WNKT: kwasu eikozapentaenowego (EPA) i dokozaheksaenowego (DHA), na układ sercowo-naczyniowy.Materiał i metody. Szczurom podawano karmę wzbogaconą w EPA, DHA lub standardową dietę kontrolną. Po 4 tygodniach rejestrowano potencjały czynnościowe z powierzchni serca, badano wewnątrzkomórkowy obieg Ca 2+ w izolowanych kardiomiocytach oraz echokardiograficznie oszacowano funkcję i wymiary lewej komory serca.Wyniki. Dieta wzbogacona w EPA i DHA nie miała wpływu na frakcję wyrzucania, grubość ściany i średnicę lewej komory. Dieta ...
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