title: Losartan but not enalaprilat acutely reduces reperfusion ventricular tachyarrhythmias in hypertrophied rat hearts after low-flow ischaemia.
abstract: Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti-arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti-arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low-flow ischaemia and reperfusion. In dose-finding experiments in non-hypertrophied isolated perfused hearts, we performed dose-response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD(90%)) and ventricular fibrillation (VF) threshold. Subsequently, we determined the effects of losartan and enalaprilat (in therapeutically relevant concentrations) on ventricular tachyarrhythmias induced by low-flow ischaemia/reperfusion in hearts demonstrating left ventricular (LV) hypertrophy 70 days after aortic banding. We found that neither drug significantly affected MAPD(90%) (1 nM-1 mM) or VF threshold (1 microM losartan and 10 microM enalaprilat) in non-hypertrophied hearts. Similarly in hypertrophied hearts, neither drug significantly affected the incidence or the duration of ventricular tachyarrhythmias (ventricular tachycardia and VF) during low-flow ischaemia. However, 1 microM losartan significantly reduced the duration of ventricular tachyarrhythmias during reperfusion. In conclusion, neither losartan nor enalaprilat is acutely anti-arrhythmic in hypertrophied rat hearts during low-flow ischaemia. During reperfusion, however, losartan but not enalaprilat exerts acute anti-arrhythmic effects.
authors.affiliation: Experimental Cardiology Research Group, Department of Research, University Hospital of Basel, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Butz
authors.forename: Sergey
authors.initials: S
authors.lastname: Driamov
authors.forename: Andrea
authors.initials: A
authors.lastname: Remondino
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bellahcene
authors.forename: Konstantin
authors.initials: K
authors.lastname: Beier
authors.forename: André
authors.initials: A
authors.lastname: Ziegler
authors.forename: Peter T
authors.initials: PT
authors.lastname: Buser
authors.forename: Christian E
authors.initials: CE
authors.lastname: Zaugg
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications; D066298:In Vitro Techniques; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000517:prevention & control*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D015773:Enalaprilat; D019808:Losartan