In vivo studies of Scn5a+/- mice modeling Brugada syndrome demonstrate both conduction and repolarization abnormalities.

Journal of Electrocardiology
Claire A MartinChristopher L-H Huang

Abstract

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. 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. 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.

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Citations

Jul 23, 2011·Pflügers Archiv : European journal of physiology·Claire A MartinChristopher L-H Huang
Mar 8, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Claire A MartinChristopher L-H Huang
Nov 26, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Claire A MartinChristopher L-H Huang
Jan 3, 2013·The Journal of Clinical Investigation·Alfred L George
Oct 20, 2011·International Heart Journal·Masayoshi KofuneAtsushi Hirayama
Dec 30, 2015·Progress in Biophysics and Molecular Biology·Colin H PetersPeter C Ruben
Aug 22, 2013·Pediatric Cardiology·Yanmin ZhangJames A Fraser
Oct 30, 2015·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Boris RudicTheano Papavassiliu
Dec 16, 2016·Physiological Reviews·Christopher L-H Huang
Mar 5, 2019·Expert Opinion on Drug Discovery·Ben Waldau
Apr 30, 2019·International Journal of Molecular Sciences·Franziska SendfeldRamon Brugada
Jul 10, 2013·The Journal of Physiology·Gareth D K MatthewsChristopher L-H Huang
Sep 28, 2017·Clinical and Experimental Pharmacology & Physiology·Shiraz AhmadChristopher L-H Huang
Dec 22, 2020·European Journal of Pharmacology·Daniel AmstetterHannes Todt
Feb 13, 2021·Cardiovascular Research·Paloma Nieto-MarínUNKNOWN I T A C A Consortium Investigators

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