Document Detail

Combined sodium and calcium channel blockade in prevention of lethal arrhythmias.
MedLine Citation:
PMID:  12717095     Owner:  NLM     Status:  MEDLINE    
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.
Philip B Adamson; Emilio Vanoli; Toshiro Shibano; Robert D Foreman; Peter J Schwartz
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  41     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-04-28     Completed Date:  2004-03-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  665-70     Citation Subset:  IM    
Department of Physiology, Cardiovascular Diseases Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology
Anti-Arrhythmia Agents / pharmacology,  therapeutic use
Calcium Channel Blockers / pharmacology,  therapeutic use*
Death, Sudden, Cardiac / etiology,  prevention & control*
Depression, Chemical
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*
Reg. No./Substance:
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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