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Remodeling of ventricular repolarization in a chronic doxorubicin cardiotoxicity rat model.
MedLine Citation:
PMID:  22429163     Owner:  NLM     Status:  Publisher    
Doxorubicin, one of the most effective anticancer drugs, is characterized by severe cardiotoxic effects, which induce cardiac remodeling and congestive heart failure. The aim of the study was to evaluate remodeling of ventricular repolarization heterogeneity in chronic doxorubicin cardiotoxicity in rats. Doxorubicin cardiotoxicity was produced by six equal intraperitoneal injections of the drug in a cumulative dose of 15 mg/kg in a 2-week period. Electrophysiological mapping of the ventricular epicardium in situ was performed 6 weeks after the last injection of doxorubicin. Activation-recovery intervals (ARIs) were used for the evaluation of the heterogeneity in repolarization durations. The major findings were as follows: (1) ARIs on the ventricular epicardium of both ventricles were significantly prolonged in the doxorubicin group and (2) this inhomogeneous prolongation of ARIs on the ventricular epicardium resulted in (i) the increase in the dispersion of repolarization across the ventricular epicardium and (ii) the inhomogeneous alterations of the regional ARI gradients on the ventricular epicardium. These changes in repolarization could explain the electrocardiographic alterations, that is, the prolongation of the QT interval and flattening of the T wave.
Sergey Kharin; Valeria Krandycheva; Alena Tsvetkova; Marina Strelkova; Dmitry Shmakov
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-19
Journal Detail:
Title:  Fundamental & clinical pharmacology     Volume:  -     ISSN:  1472-8206     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8710411     Medline TA:  Fundam Clin Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors. Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.
Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya st., Syktyvkar, Komi Republic 167000, Russia Department of Physiology, Komi Branch of Kirov State Medical Academy, 11, Babushkin st., Syktyvkar, Komi Republic 167000, Russia.
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