title: Heart rate slowing for myocardial dysfunction/heart failure.
abstract: Heart failure is a major health problem, and is one of the few cardiovascular diseases that increased its prevalence over the last decade. Increased heart rate, generally observed in patients with heart failure, is involved in the deterioration of cardiac pump function. However, the effects of 'pure' heart rate reduction on the progression of heart failure are unknown. In a rat model of heart failure, ivabradine, a blocker of I(f) channels reduces dose-dependently heart rate without modification of blood pressure. This heart rate reduction is associated with an improvement in cardiac function. After chronic administration, this improvement of cardiac function persists after ivabradine withdrawal, revealing an improvement in intrinsic myocardial function. This beneficial effect could be explained by direct effects of heart rate reduction induced by ivabradine, i.e. improved myocardial oxygen supply to demand ratio, and/or myocardial tissular effects induced by chronic decrease in heart rate such, i.e. decreased extracellular collagen accumulation, increased myocardial microcirculation. In conclusion, 'pure' chronic heart rate reduction can be beneficial in heart failure.
authors.affiliation: INSERM U644, Faculté de Médecine et de Pharmacie, Rouen, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Mulder
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D000077550:Ivabradine; D009206:Myocardium / Q000737:chemistry; D051381:Rats; D012849:Sinoatrial Node / Q000187:drug effects
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D007473:Ion Channels; D000077550:Ivabradine