Document Detail


Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling.
MedLine Citation:
PMID:  20952661     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to investigate the effect of chronic heart rate (HR) reduction with the hyperpolarization-activated current inhibitor ivabradine on the global phenotype of left ventricular (LV) remodeling in a ligated rat model. Seven days after coronary artery ligation, Wistar rats received ivabradine (10 mg · kg(-1) · day(-1) administered in drinking water) [myocardial infarction + ivabradine (MI+IVA), n = 22] or vehicle only (drinking water) (MI, n = 20) for 90 days. A sham group (n = 20) was included for model validation. MI+IVA rats had 12% lower HR (P < 0.01), improved LV volumes, 15% higher LV ejection fraction (LVEF, P < 0.01) than MI rats, and 33% reductions in both plasma atrial natriuretic peptide (ANP, P = 0.052) and cardiac hydroxyproline. Using patch-clamp, action potential duration was reduced and transient outward current density increased (P < 0.05). Cardiac energy metabolism was also improved (+33% creatine phosphate, P < 0.001; +15% ATP; and +9% energy charge, P < 0.05). Significant correlations were found between HR and parameters of cardiac metabolism, ANP, and LVEF (all P < 0.05). The HR-reducing properties of ivabradine prevent changes in the global phenotype of LV remodeling in the rat, optimize energy consumption, and avoid electrophysiological and structural remodeling.
Authors:
Claudio Ceconi; Laura Comini; Silvia Suffredini; Francesca Stillitano; Muriel Bouly; Elisabetta Cerbai; Alessandro Mugelli; Roberto Ferrari
Publication Detail:
Type:  Journal Article     Date:  2010-10-15
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  300     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H366-73     Citation Subset:  IM    
Affiliation:
Department of Cardiology, University of Ferrara, Ferrara, Italy. claudio.ceconi@unife.it
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects,  physiology
Animals
Benzazepines / pharmacology*
Electrocardiography
Energy Metabolism / drug effects,  physiology
Heart / drug effects*,  physiopathology
Heart Rate / drug effects*,  physiology
Male
Myocardial Infarction / metabolism,  physiopathology
Myocardium / metabolism
Rats
Rats, Wistar
Ventricular Function, Left / drug effects*,  physiology
Ventricular Remodeling / drug effects*,  physiology
Chemical
Reg. No./Substance:
0/Benzazepines; 155974-00-8/ivabradine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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