In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 300, No. 1 ( 2011-01), p. H366-H373
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.01117.2009
Language:
English
Publisher:
American Physiological Society
Publication Date:
2011
detail.hit.zdb_id:
1477308-9
SSG:
12
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