Publication Date

12-1-2016

Journal

The Texas Heart Journal

DOI

10.14503/THIJ-15-5495

PMID

28100964

Publication Date(s)

December 2016

Language

English

PMCID

PMC5179150

PubMedCentral® Posted Date

12-1-2016

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

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

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.

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