| Effects of ranolazine on the exercise capacity of rats with chronic heart failure induced by myocardial infarction. | |
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MedLine Citation:
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PMID: 8877580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ranolazine was previously shown to stimulate cardiac glucose oxidation. Dichloroacetate (DCA) also does and was shown to improve exercise capacity in animals, but it has long-term toxicity problems. To test the hypothesis that ranolazine would increase exercise performance in the chronic heart failure (CHF) condition, we compared the exercise endurance capacities of rats with a surgically induced myocardial infarction (MI) with those of noninfarcted sham-operated (Sham) controls both before and after 14 and 28 days of drug administration. Chronic administration of ranolazine, 50 mg/kg twice daily (b.i.d.) oral, significantly reduced the endurance capacities of both Sham and MI rats (measured after a 12-h fast to reduce liver glycogen stores), as indicated by the reductions in run times to fatigue during a progressive treadmill test. Ranolazine produced reductions in resting plasma lactate and glucose concentrations of animals fasted for 12 h (consistent with stimulating glucose oxidation); however, tissue glycogen concentrations measured in various locomotor muscles located in the animal's hindlimb were unaffected when measured 48 h after the last treadmill test and after 12 h of fasting. Chronic administration of ranolazine did not increase the endurance capacity of rats with CHF induced by MI at the dosage and with the protocol used. To the contrary, the chronic administration of ranolazine appears to reduce the work capacity of all rats, suggesting that this drug may not be useful therapeutically in the treatment of CHF. Whether the decrements in endurance capacity produced by ranolazine are related to the high plasma concentrations of the drug produced in this study as compared with previous studies in humans remains subject to further experimentation. |
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Authors:
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A Aaker; J G McCormack; T Hirai; T I Musch |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 28 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1996 Sep |
Date Detail:
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Created Date: 1997-03-03 Completed Date: 1997-03-03 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 353-62 Citation Subset: IM; S |
Affiliation:
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Department of Anatomy and Physiology, Kansas State University, Manhattan 66506, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetanilides Animals Blood Glucose / analysis Cardiac Output, Low / complications, physiopathology* Enzyme Inhibitors / therapeutic use* Female Glycogen / analysis Lactic Acid / blood Muscle, Skeletal / drug effects, metabolism Myocardial Infarction / complications*, drug therapy Physical Exertion / drug effects*, physiology Piperazines / blood, therapeutic use* Rats Rats, Wistar |
| Grant Support | |
ID/Acronym/Agency:
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AG11535/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acetanilides; 0/Blood Glucose; 0/Enzyme Inhibitors; 0/Piperazines; 110445-25-5/ranolazine; 50-21-5/Lactic Acid; 9005-79-2/Glycogen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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