Document Detail


In vivo studies of Scn5a+/- mice modeling Brugada syndrome demonstrate both conduction and repolarization abnormalities.
MedLine Citation:
PMID:  20638671     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: We investigate the extent to which the electrocardiographic (ECG) properties of intact Scn5a+/- mice reproduce the corresponding clinical Brugada syndrome phenotype and use this model to investigate the role of conduction and repolarization abnormalities in the arrhythmogenic mechanism.
METHODS AND RESULTS: The ECGs were obtained from anesthetized wild-type and Scn5a+/- mice, before and after administration of the known pro- and antiarrhythmic agents flecainide and quinidine. The ECG intervals were measured and their dispersions calculated. Scn5a+/- hearts showed ventricular arrhythmias, ST elevation, and conduction disorders including increased QT dispersion, accentuated by flecainide. Quinidine did not cause ventricular arrhythmias but exerted variable effects on ST segments and worsened conduction abnormalities.
CONCLUSIONS: The ECG features in an Scn5a+/- mouse establish it as a suitable model for Brugada syndrome and demonstrate abnormal conduction and repolarization phenomena. Altered QT dispersion, taken to indicate increased transmural repolarization gradients, may be useful in clinical risk stratification.
Authors:
Claire A Martin; Yanmin Zhang; Andrew A Grace; Christopher L-H Huang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-17
Journal Detail:
Title:  Journal of electrocardiology     Volume:  43     ISSN:  1532-8430     ISO Abbreviation:  J Electrocardiol     Publication Date:    2010 Sep-Oct
Date Detail:
Created Date:  2010-08-23     Completed Date:  2011-01-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0153605     Medline TA:  J Electrocardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  433-9     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom. clairemartin@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Arrhythmia Agents / pharmacology
Brugada Syndrome / physiopathology*
Disease Models, Animal*
Electrocardiography*
Flecainide / pharmacology
Heart Conduction System / physiopathology*
Mice
Mice, Inbred Strains
Phenotype
Quinidine / pharmacology
Grant Support
ID/Acronym/Agency:
//Biotechnology and Biological Sciences Research Council; //British Heart Foundation; //Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 54143-55-4/Flecainide; 56-54-2/Quinidine

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