title: Differences in arrhythmogenicity between the canine right ventricular outflow tract and anteroinferior right ventricle in a model of Brugada syndrome.
abstract: BACKGROUND
  The Brugada syndrome is characterized by ST-segment elevation on the ECG, especially in the right precordial leads sensitive to the right ventricular outflow tract (RVOT).
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the hypothesis that right ventricular electrophysiologic heterogeneity caused arrhythmogenicity in the Brugada syndrome.
  
  
  METHODS
  Action potentials (APs) were mapped on the epicardium of 14 RVOT preparations and on the transmural surfaces of 15 pairs of RVOT and right ventricular anteroinferior (RVAI) preparations isolated from canine hearts. Brugada ECG and arrhythmias were induced with pilsicainide (2.5-12.5 micromol/L), pinacidil (1.25-12.5 micromol/L), and terfenadine (2.0 micromol/L).
  
  
  RESULTS
  Low doses of drugs elevated the J-ST segment and induced APs with both short and long action potential durations (APDs) in contiguous RVOT epicardial regions. In addition, APs in the RVOT had a larger phase 1 notch and longer APD than in RVAI. The longest APDs were in the epicardium in RVOT but in the endocardium in RVAI regions. High doses of drugs eliminated the phase 2 dome of the AP and abbreviated APDs in the epicardium but not in endocardium and reduced the epicardial heterogeneity of APs but increased the transmural gradient of APD in 14 (93%) of the RVOT preparations. In contrast, abbreviations of epicardial APDs occurred in only 4 (27%) of the RVAI preparations. Ventricular tachycardia occurred more frequently in the RVOT (47%) than in paired RVAI preparations (7%). Blocking the transient outward current reduced the heterogeneity of APs and eliminated arrhythmogenicity in all preparations.
  
  
  CONCLUSIONS
  Compared with the RVAI region, the RVOT has greater electrophysiologic heterogeneity that contributes to arrhythmogenicity in this model of Brugada syndrome.
authors.affiliation: Department of Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Zipes
authors.forename: Shiho T
authors.initials: ST
authors.lastname: Morita
authors.forename: Jiashin
authors.initials: J
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D053840:Brugada Syndrome / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D008297:Male; D020110:Pinacidil / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D016278:Ventricular Function, Right
chemical_list: D000889:Anti-Arrhythmia Agents; D020110:Pinacidil; D011802:Quinidine