Ivabradine Protects Against Ventricular Arrhythmias in Acute Myocardial Infarction in the Rat. Issue 6 (June 2014)

• Record Type: Journal Article
• Authors: Mackiewicz, Urszula; Gerges, Joseph Y.; Chu, Sandy; Duda, Monika; Dobrzynski, Halina; Lewartowski, Bohdan; Mączewski, Michał
• Is Part Of: Journal of cellular physiology. Volume 229:Issue 6(2014:Jun.)
• Page Start: 813
• Page End: 823
• Publication Date: 2014-06
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24507
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jcp24507-sec-0001" sec-type="section"> <p>Ventricular arrhythmias are an important cause of mortality in the acute myocardial infarction (MI). To elucidate effect of ivabradine, pure heart rate (HR) reducing drug, on ventricular arrhythmias within 24 h after non‐reperfused MI in the rat. ECG was recorded for 24 h after MI in untreated and ivabradine treated rats and episodes of ventricular tachycardia/fibrillation (VT/VF) were identified. Forty‐five minutes and twenty‐four hours after MI epicardial monophasic action potentials (MAPs) were recorded, cardiomyocyte Ca<sup>2+</sup> handling was assessed and expression and function of ion channels were studied. Ivabradine reduced average HR by 17%. Combined VT/VF incidence and arrhythmic mortality were higher in MI versus MI + Ivabradine rats. MI resulted in (1) increase of Ca<sup>2+</sup> sensitivity of ryanodine receptors 24 h after MI; (2) increase of HCN4 expression in the left ventricle (LV) and funny current (I<sub>F</sub>) in LV cardiomyocytes 24 h after MI, and (3) dispersion of MAP duration both 45 min and 24 h after MI. Ivabradine partially prevented all these three potential proarrhythmic effects of MI. Ivabradine is antiarrhythmic in the acute MI in the rat. Potential mechanisms include prevention of: diastolic Ca<sup>2+</sup>‐leak from sarcoplasmic reticulum, upregulation of I<sub>F</sub> current in LV and dispersion of cardiac repolarization. Ivabradine could be an attractive antiarrhythmic agent in the setting of acute MI. J. Cell. Physiol. 229: 813–823, 2014. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>