Document Detail


Cardiac ventricular repolarization reserve: a principle for understanding drug-related proarrhythmic risk.
MedLine Citation:
PMID:  21545574     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiac repolarization abnormalities can be caused by a wide range of cardiac and non-cardiac compounds and may lead to the development of life-threatening Torsades de Pointes (TdP) ventricular arrhythmias. Drug-induced torsades de pointes is associated with unexpected and unexplained sudden cardiac deaths resulting in the withdrawal of several compounds in the past. To better understand the mechanism of such unexpected sudden cardiac deaths, the concept of repolarization reserve has recently emerged. According to this concept, pharmacological, congenital or acquired impairment of one type of transmembrane ion channel does not necessarily result in excessive repolarization changes because other repolarizing currents can take over and compensate. In this review, the major factors contributing to repolarization reserve are discussed in the context of their clinical significance in physiological and pathophysiological conditions including drug administration, genetic defects, heart failure, diabetes mellitus, gender, renal failure, hypokalaemia, hypothyroidism and athletes' sudden deaths. In addition, pharmacological support of repolarization reserve as a possible therapeutic option is discussed. Some methods for the quantitative estimation of repolarization reserve are also recommended. It is concluded that repolarization reserve should be considered by safety pharmacologists to better understand, predict and prevent previously unexplained drug-induced sudden cardiac deaths.
Authors:
András Varró; István Baczkó
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  British journal of pharmacology     Volume:  164     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-08     Completed Date:  2012-02-02     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  14-36     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary. a.varro@phcol.szote.u-szeged.hu
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / chemically induced*,  physiopathology*
Heart / drug effects*,  physiopathology*
Heart Conduction System / drug effects,  physiopathology
Heart Ventricles / drug effects,  physiopathology
Humans
Pharmaceutical Preparations / adverse effects*
Risk Factors
Torsades de Pointes / chemically induced,  physiopathology
Chemical
Reg. No./Substance:
0/Pharmaceutical Preparations
Comments/Corrections

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


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