| Combined sodium and calcium channel blockade in prevention of lethal arrhythmias. | |
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MedLine Citation:
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PMID: 12717095 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Anti-arrhythmic compounds with multiple actions reduce arrhythmic death risk in post-myocardial infarction (MI) patients. Sudden death prevention, however, may rely more on implantable defibrillators than anti-arrhythmic drugs due to ineffective pharmacologic intervention. Widespread use of implantable defibrillators should not obscure the need for development of new anti-arrhythmic drugs. This study tested the hypothesis that combined blockade of I(Na) and I(Ca(L)) prevents ischemia-dependent ventricular fibrillation (VF) in conscious dogs after MI. I(Na) and I(Ca(L)) blockade was accomplished with levosemotiadil in 11 dogs known to be at high risk for VF during 2 min of coronary occlusion during submaximal treadmill exercise 30 days after MI. Negative chronotropic effect of levosemotiadil was examined using the heart rate response to isoproterenol and comparing it with response to propranolol. Levosemotiadil prevented VF in 64% (7 of 11) of the high-risk animals. Heart rate responses to myocardial ischemia and to graded doses of isoproterenol were blunted by the high dose of levosemotiadil. Propranolol prevented VF in 73% (8 of 11) of the dogs. Levosemotiadil had approximately one half the beta-blocking activity of propranolol. The combination of I(Na) and I(Ca(L)) channel blockade coupled with partial beta-adrenergic blockade was equally effective in preventing VF as propranolol. |
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Authors:
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Philip B Adamson; Emilio Vanoli; Toshiro Shibano; Robert D Foreman; Peter J Schwartz |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 41 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2003 May |
Date Detail:
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Created Date: 2003-04-28 Completed Date: 2004-03-18 Revised Date: 2006-11-15 |
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: 665-70 Citation Subset: IM |
Affiliation:
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Department of Physiology, Cardiovascular Diseases Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. philip-adamson@ouhsc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Antagonists
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pharmacology Animals Anti-Arrhythmia Agents / pharmacology, therapeutic use Calcium Channel Blockers / pharmacology, therapeutic use* Death, Sudden, Cardiac / etiology, prevention & control* Depression, Chemical Dogs Drug Synergism Drug Therapy, Combination Heart Rate / drug effects* Isoproterenol / pharmacology Myocardial Infarction / complications Physical Conditioning, Animal Propranolol / pharmacology Sodium Channel Blockers / pharmacology, therapeutic use* Thiazoles / pharmacology Ventricular Fibrillation / etiology, mortality, prevention & control* |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Antagonists; 0/Anti-Arrhythmia Agents; 0/Calcium Channel Blockers; 0/Sodium Channel Blockers; 0/Thiazoles; 116476-14-3/sesamodil; 525-66-6/Propranolol; 7683-59-2/Isoproterenol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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