| Cardioprotective effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on cardiac dysfunction induced by ischemia/reperfusion in isolated rat hearts. | |
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MedLine Citation:
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PMID: 11093075 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inhibition of fatty acid metabolite accumulation may be beneficial for treatment of cardiac dysfunction induced by ischemia. MET-88, 3-(2,2,2-trimethylhydrazinium)propionate dihydrate, inhibits gamma-butyrobetaine hydroxylase which catalyzes conversion of gamma-butyrobetaine to carnitine. In this study, we investigated whether MET-88 has cardioprotective effects against cardiac dysfunction induced by ischemia/reperfusion. Rats were divided into four groups: (1) control; (2) MET-88 at 50 mg/kg; (3) MET-88 at 100 mg/kg; (4) nifedipine at 30 mg/kg. MET-88 was administered orally once a day for 10 days, and nifedipine was administered orally 30 min before the experiments. Cardiac functions (heart rate, left ventricular systolic pressure and coronary flow) were measured in rat working heart preparations for 30 min under ischemia followed by 20 min under reperfusion. Myocardial carnitine levels were measured at the end of the experiments. Before ischemia, MET-88 did not affect cardiac functions, but nifedipine significantly increased only coronary flow. Under the ischemic condition, cardiac functions were markedly decreased in all groups. During reperfusion, MET-88 and nifedipine promoted recovery of cardiac functions and decreased the incidence of ventricular fibrillation. MET-88 also prevented the accumulation of long-chain acylcarnitine induced by ischemia. These results indicated that MET-88 protected against cardiac dysfunction in ischemia/reperfusion, and preventing the accumulation of long-chain acylcarnitine may be responsible for the cardioprotective effects. |
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Authors:
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Y Hayashi; K Tajima; T Kirimoto; H Miyake; N Matsuura |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Pharmacology Volume: 61 ISSN: 0031-7012 ISO Abbreviation: Pharmacology Publication Date: 2000 Nov |
Date Detail:
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Created Date: 2001-01-09 Completed Date: 2001-01-09 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0152016 Medline TA: Pharmacology Country: SWITZERLAND |
Other Details:
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Languages: eng Pagination: 238-43 Citation Subset: IM |
Copyright Information:
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Copyright 2000 S. Karger AG, Basel. |
Affiliation:
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Pharmacology Research Laboratory, Taiho Pharmaceutical Co. Ltd., Tokushima, Japan. yucky@mail.netwave.or.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carnitine / metabolism Enzyme Inhibitors / therapeutic use* Heart Function Tests Hemodynamics / drug effects Lactic Acid / metabolism Male Methylhydrazines / therapeutic use* Mixed Function Oxygenases / antagonists & inhibitors* Myocardial Contraction / drug effects Myocardial Reperfusion Injury / enzymology, physiopathology, prevention & control* Myocardium / metabolism Nifedipine / pharmacology Rats Rats, Sprague-Dawley Ventricular Fibrillation / drug therapy gamma-Butyrobetaine Dioxygenase |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Methylhydrazines; 21829-25-4/Nifedipine; 50-21-5/Lactic Acid; 541-15-1/Carnitine; 76144-81-5/3-(2,2,2-trimethylhydrazine)propionate; EC 1.-/Mixed Function Oxygenases; EC 1.14.11.1/gamma-Butyrobetaine Dioxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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