title: Ivabradine protects against ventricular arrhythmias in acute myocardial infarction in the rat.
abstract: 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(2+) 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(2+) sensitivity of ryanodine receptors 24 h after MI; (2) increase of HCN4 expression in the left ventricle (LV) and funny current (IF) 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(2+)-leak from sarcoplasmic reticulum, upregulation of IF current in LV and dispersion of cardiac repolarization. Ivabradine could be an attractive antiarrhythmic agent in the setting of acute MI.
authors.affiliation: Department of Clinical Physiology, Medical Center of Postgraduate Education, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Mackiewicz
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Gerges
authors.forename: Sandy
authors.initials: S
authors.lastname: Chu
authors.forename: Monika
authors.initials: M
authors.lastname: Duda
authors.forename: Halina
authors.initials: H
authors.lastname: Dobrzynski
authors.forename: Bohdan
authors.initials: B
authors.lastname: Lewartowski
authors.forename: Michał
authors.initials: M
authors.lastname: Mączewski
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D001552:Benzazepines / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D000077550:Ivabradine; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000188:drug therapy*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D015221:Potassium Channels; D000077550:Ivabradine; D002118:Calcium