| Effect of graded heart rate reduction with ivabradine on myocardial oxygen consumption and diastolic time in exercising dogs. | |
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MedLine Citation:
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PMID: 14569053 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lowering heart rate reduces myocardial oxygen consumption (MVO2) and produces potent anti-ischemic effects. The development of selective heart rate-reducing agents represents an alternative approach to the use of beta-blockers. Therefore, our goal was to establish the dose-response curve of the effects of ivabradine (If channel inhibitor) on MVO2 and diastolic time. Seven conscious and chronically instrumented dogs were investigated during exercise at spontaneous and paced heart rate (250 beats/min) after administration of increasing doses of ivabradine (0.25, 0.5, and 1 mg/kg i.v.). During exercise, ivabradine dose dependently and significantly reduced the exercise-induced tachycardia (-17, -21, and -32% at 0.25, 0.5, and 1 mg/kg, respectively, versus saline) without altering myocardial contractility nor mean ejection wall stress. A linear relationship between heart rate (HR) and MVO2 was demonstrated (MVO2 = 0.044 x HR - 1.4; r = 0.987). These effects of ivabradine on MVO2 were abolished by atrial pacing. Similarly, ivabradine dose dependently increased diastolic time without altering the inverse and non linear relationship between diastolic time and heart rate observed with saline. In conclusion, selective heart rate reduction with ivabradine dose dependently increases diastolic time and reduces MVO2 with a linear relationship between heart rate and MVO2. The lack of "on-off" pharmacological profile will predict the possibility of using a wide range of dose regimen. |
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Authors:
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Patrice Colin; Bijan Ghaleh; Xavier Monnet; Luc Hittinger; Alain Berdeaux |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-10-20 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 308 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2004-01-13 Completed Date: 2004-02-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 236-40 Citation Subset: IM |
Affiliation:
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Laboratoire de Pharmacologie, Institut National de la Santé et de la Recherche Médicale E 00.01, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Benzazepines / pharmacology* Dogs Heart Rate / drug effects* Myocardial Contraction Oxygen Consumption / drug effects* Physical Conditioning, Animal / physiology* Time Factors Ventricular Function, Left / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Benzazepines; 155974-00-8/ivabradine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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