title: Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model: high-resolution optical mapping study.
abstract: OBJECTIVE
  We examined how repolarization and depolarization abnormalities contribute to the development of extrasystoles and subsequent ventricular fibrillation (VF) in a model of the Brugada syndrome.
  
  
  BACKGROUND
  Repolarization and depolarization abnormalities have been considered to be mechanisms of the coved-type ST-segment elevation (Brugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome.
  
  
  METHODS
  We used high-resolution (256 x 256) optical mapping techniques to study arterially perfused canine right ventricular wedges (n = 20) in baseline and in the Brugada-ECG produced by administration of terfenadine (5 micromol/l), pinacidil (2 micromol/l), and pilsicainide (5 micromol/l). We recorded spontaneous episodes of phase 2 re-entrant (P2R)-extrasystoles and subsequent self-terminating polymorphic ventricular tachycardia (PVT) or VF under the Brugada-ECG condition and analyzed the epicardial conduction velocity and action potential duration (APD) restitutions in each condition.
  
  
  RESULTS
  Forty-one episodes of spontaneous P2R-extrasystoles in the Brugada-ECG were successfully mapped in 9 of 10 preparations, and 33 of them were originated from the maximum gradient of repolarization (GR(max): 176 +/- 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GR(max) was not different between PVT and VF. Wave-break during the first P2R-extrasystole produced multiple wavelets in all VF cases, whereas no wave-break or wave-break followed by wave collision and termination occurred in PVT cases. Moreover, conduction velocity restitution was shifted lower and APD restitution was more variable in VF cases than in PVT cases.
  
  
  CONCLUSIONS
  Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.
authors.affiliation: Department of Cardiovascular Dynamics, Research Institute, National Cardiovascular Center, Suita, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aiba
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hidaka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Uemura
authors.forename: Takashi
authors.initials: T
authors.lastname: Noda
authors.forename: Can
authors.initials: C
authors.lastname: Zheng
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kamiya
authors.forename: Masashi
authors.initials: M
authors.lastname: Inagaki
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000200:Action Potentials; D000818:Animals; D002317:Cardiovascular Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods*; D004699:Endocardium; D006329:Heart Conduction System / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced; D006352:Heart Ventricles / Q000187:drug effects; D008012:Lidocaine / Q000009:adverse effects / Q000031:analogs & derivatives; D008297:Male; D010496:Pericardium; D020110:Pinacidil / Q000009:adverse effects; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000503:physiopathology; D016593:Terfenadine / Q000009:adverse effects; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D002317:Cardiovascular Agents; D020110:Pinacidil; D016593:Terfenadine; D008012:Lidocaine; C042288:pilsicainide