Document Detail


Early after-depolarizations and torsade de pointes: implications for the control of cardiac arrhythmias by prolonging repolarization.
MedLine Citation:
PMID:  8293755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Common clinical features in drug-induced torsade de pointes include hypokalemia and cycle-length prolongation just prior to initiation of the arrhythmia. In canine Purkinje fibres, drugs known to be associated with torsade de pointes, such as quinidine, sotalol or N-acetylprocainamide, consistently produce early after-depolarizations (EADs) and triggered activity at slow drive rates; for quinidine, these abnormalities are exaggerated by low extracellular potassium. Triggered activity can be abolished in vitro in two ways. First, action-potential shortening with abolition of EADs can be accomplished by increasing stimulation rates, beta-stimulation and action-potential shortening antiarrhythmics such as lidocaine. Second, triggered activity can be suppressed, with less prominent effects on EADs, by magnesium, alpha- and/or beta-adrenergic blockade and calcium-channel blockers. The parallels between these in vitro findings and clinical torsade de pointes suggest that EADs and triggered activity play a role in the genesis of the clinical arrhythmia. Further research directed at determining the mechanisms underlying the cellular abnormalities and their propagation to the whole heart should yield information that will increase the safety of antiarrhythmic therapy.
Authors:
D M Roden
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  European heart journal     Volume:  14 Suppl H     ISSN:  0195-668X     ISO Abbreviation:  Eur. Heart J.     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1994-03-03     Completed Date:  1994-03-03     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  56-61     Citation Subset:  IM    
Affiliation:
Vanderbilt University, Division of Clinical Pharmacology, Nashville, TN 37232-6602.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects
Animals
Anti-Arrhythmia Agents / pharmacology*
Heart Conduction System / drug effects*,  physiopathology
Humans
Long QT Syndrome / chemically induced,  physiopathology*
Potassium Channels / drug effects
Purkinje Fibers / drug effects
Torsades de Pointes / chemically induced,  physiopathology*
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Potassium Channels

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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