title: In vivo studies of Scn5a+/- mice modeling Brugada syndrome demonstrate both conduction and repolarization abnormalities.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom. clairemartin@gmail.com
authors.forename: Claire A
authors.initials: CA
authors.lastname: Martin
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Grace
authors.forename: Christopher L-H
authors.initials: CL
authors.lastname: Huang
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D053840:Brugada Syndrome / Q000503:physiopathology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005424:Flecainide / Q000494:pharmacology; D006329:Heart Conduction System / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D011802:Quinidine / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D011802:Quinidine; D005424:Flecainide