| Ivabradine reduces heart rate while preserving metabolic fluxes and energy status of healthy normoxic working hearts. | |
| | |
MedLine Citation:
|
PMID: 21257916 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Heart rate reduction (HRR) is an important target in the management of patients with chronic stable angina. Most available drugs for HRR such as β-blockers have adverse effects, including on cardiac energy substrate metabolism, a well-recognized determinant of cardiac homeostasis. This study aimed at (i) testing whether HRR by ivabradine (IVA) alters substrate metabolism in the healthy normoxic working heart and (ii) comparing the effect of IVA to that of the β-blocker metoprolol (METO). This was assessed using our well-established model of ex vivo mouse heart perfusion in the working mode, which enables concomitant evaluation of myocardial contractility and metabolic fluxes using (13)C-labeled substrates. Hearts were perfused in the absence (controls; n=10) or presence of IVA (n=10, 3 μM) with or without atrial pacing to abolish HRR in IVA group. IVA significantly reduced HR (35±5%), increased stroke volume (39±9%), while maintaining similar cardiac output, contractility, power and efficiency. Effects of IVA on HR and stroke volume were reversed by atrial pacing. At the metabolic level, IVA did not impact on substrate selection to citrate formation, rates of glycolysis or tissue levels of high energy phosphates. In contrast, METO, at concentrations up to 40 μM, decreased markedly cardiac function (flow: 25±6%; stroke volume: 30±10%; contractility: 31±9%), as well as glycolysis (2.9-fold), but marginally affected HR. Collectively, these results demonstrate that IVA selectively reduces HR while preserving energy substrate metabolism of normoxic healthy working mouse hearts perfused ex vivo, a model that mimics to some extent the denervated transplanted heart. Our results provide the impetus for testing selective HRR by IVA on cardiac substrate metabolism in pathological models. |
| | |
Authors:
|
Benjamin Lauzier; Fanny Vaillant; Roselle Gelinas; Bertrand Bouchard; Roger W Brownsey; Eric Thorin; Jean-Claude Tardif; Christine Des Rosiers |
Related Documents
:
|
1638706 - Evidence for transient linking of atrial excitation during atrial fibrillation in humans. 14688506 - Prevalence, prognostic significance, and treatment of atrial fibrillation in congestive... 17382646 - Superiority of cut-and-sew technique for the cox maze procedure: comparison with radiof... 8353866 - Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. rele... 6320666 - Norepinephrine increases beta-receptors and adenylate cyclase in canine myocardium. 21616286 - The v(2) transition ratio a new electrocardiographic criterion for distinguishing left ... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-1-21 |
Journal Detail:
|
Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2011-1-24 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1LPPCE. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Soluble guanylate cyclase-?1 is required for the cardioprotective effects of inhaled nitric oxide.
Next Document: Relation between QT interval variability and cardiac sympathetic activity in hypertension.