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Influence of ivabradine on reverse remodelling during mechanical unloading.
MedLine Citation:
PMID:  23079200     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Ivabradine (Iva) has shown beneficial structural and functional effects in clinical and experimental heart failure (HF), but its action in combination with mechanical unloading (MU), such as during treatment with left ventricular assist devices (LVAD), is unknown. The aim of this study was to investigate the effects of Iva during MU, in a rodent model of HF.Methods and ResultsWe studied the chronic effects (4 weeks) of Iva (10mg/kg/day) alone, and in combination with MU (induced by heterotopic abdominal heart transplantation (HATx)) on whole heart and cellular structure, function and excitation-contraction (EC) coupling in a rodent (rat) model of HF, 12 weeks post left coronary artery (LCA) ligation. Iva's effects were compared with those of β-blockade using metoprolol ((Met), 250mg/kg/day). Iva, but not Met, reversed myocardial fibrosis, alone and in combination with MU. MU-induced restoration of deranged EC coupling was enhanced by Iva, to a greater extent than Met: both Iva and Met enhanced recovery of Ca(2+)transient amplitude and sarcoplasmic reticulum (SR) Ca(2+)content, but Iva alone maintained MU-induced normalisation of L-type Ca(2+)current and t-tubule abnormalities. Met prevented MU-induced reduction in myocardial size (myocardial atrophy); Iva had no effect on this parameter. CONCLUSIONS: Iva shows beneficial structural and EC coupling effects during MU: Iva reverses myocardial fibrosis and enhances restoration of deranged EC coupling, displaying more beneficial effects than that of Met. These results suggest that Iva may prove effective in enhancing functional recovery in heart failure patients receiving LVAD therapy.
Authors:
Manoraj Navaratnarajah; Michael Ibrahim; Urszula Siedlecka; Carin van Doorn; Adarsh Shah; Ajay Gandhi; Priyanthi Dias; Padmini Sarathchandra; Magdi H Yacoub; Cesare M Terracciano
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-18
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Harefield Heart Science Centre, Imperial College London, National Heart and Lung Institute, Laboratory of Cellular Electrophysiology, Harefield Hospital, Harefield, Middlesex, UB9 6JH, UK.
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