title: Comparative Efficacy of Nebivolol and Metoprolol to Prevent Tachycardia-Induced Cardiomyopathy in a Porcine Model.
abstract: Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model. Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were obtained at baseline and at the end of the study. At the end of week 8, the pigs were euthanized, and complete histopathologic studies were performed. All the pigs developed left ventricular cardiomyopathy but remained hemodynamically stable and survived to the end of the study. The mean left ventricular ejection fraction decreased from baseline by 34%, 20%, and 20% in the nebivolol, metoprolol, and placebo groups, respectively. These changes did not differ significantly among the 3 groups (P=0.51). Histopathologic analysis revealed mild left ventricular perivascular fibrosis with cardiomyocyte hypertrophy in 14 of the 15 pigs. Both nebivolol and metoprolol failed to prevent cardiomyopathy in our animal model of persistent tachycardia and a high catecholamine state.
authors.forename: Alireza
authors.initials: A
authors.lastname: Nazeri
authors.forename: MacArthur A
authors.initials: MA
authors.lastname: Elayda
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Segura
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Stainback
authors.forename: Joanna
authors.initials: J
authors.lastname: Nathan
authors.forename: Vei-Vei
authors.initials: VV
authors.lastname: Lee
authors.forename: Christina
authors.initials: C
authors.lastname: Bove
authors.forename: Luiz
authors.initials: L
authors.lastname: Sampaio
authors.forename: Brian
authors.initials: B
authors.lastname: Grace
authors.forename: Ali
authors.initials: A
authors.lastname: Massumi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Razavi
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D002304:Cardiac Pacing, Artificial; D009202:Cardiomyopathies / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005355:Fibrosis; D008790:Metoprolol / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D000068577:Nebivolol / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D034421:Sus scrofa; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000068577:Nebivolol; D008790:Metoprolol
keywords: Anti-arrhythmia agents/therapeutic use; arrhythmias, cardiac/prevention & control; cardiomyopathies/physiopathology; disease models, animal; heart rate/drug effects; metoprolol; nebivolol; receptors, adrenergic, beta/drug effects; swine; tachycardia/drug effects/prevention & control/physiopathology