title: Repolarization Alternans and Ventricular Arrhythmia in a Repaired Tetralogy of Fallot Animal Model.
abstract: BACKGROUND
  Ventricular arrhythmia is an important cause of late death in patients with repaired tetralogy of Fallot (rTOF). By using an rTOF canine model, we investigated the role of repolarization alternans and its electrophysiological mechanisms.
  
  
  RESULTS
  Six dogs received right ventricular outflow tract (RVOT) transannular patch, pulmonary valve destruction, and right bundle branch ablation to simulate rTOF. After 1 year, we performed high-resolution dual-voltage and calcium optical mapping to record action potentials and calcium transients on the excised right ventricular outflow tract wedges. Another 6 dogs without operation served as control. The rTOF group was more susceptible to action potential duration alternans (APD-ALT) and spatially discordant APD-ALT than control (threshold for APD-ALT: 516±36 vs 343±36 ms; P=0.017; threshold for discordant APD-ALT: 387±30 vs 310±14 ms; P=0.046). We detected 2 episodes of ventricular tachycardia in the rTOF group, but none in the control. Expressions of Kv4.3 and KChIP2 decreased in the rTOF group. Expression of connexin 43 also decreased in the rTOF group with a corresponding decrease of conduction velocity and might contribute to spatially discordant APD-ALT. We also found distinct electrophysiological features of the RVOT, including biphasic relationship between magnitude of APD-ALT and pacing cycle length, uncoupling of APD-ALT, and calcium transients alternans, and shortened APD, but unchanged, APD restitution in rTOF.
  
  
  CONCLUSIONS
  We demonstrated novel electrophysiological properties of the RVOT. In an rTOF model, the RVOT exhibits increased susceptibility to temporal and spatially discordant APD-ALT, which was not totally dependent on calcium transient alternans.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (S.N.C., J.K.W., M.H.W.).
authors.forename: Shuenn-Nan
authors.initials: SN
authors.lastname: Chiu
authors.affiliation: Department of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (C.T.T., L.Y.L., L.P.L., J.L.L.).
authors.forename: Chia-Ti
authors.initials: CT
authors.lastname: Tsai
authors.affiliation: Department of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (C.T.T., L.Y.L., L.P.L., J.L.L.).
authors.forename: Lian-Yu
authors.initials: LY
authors.lastname: Lin
authors.affiliation: Department of Surgery, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (S.C.H., Y.S.C.).
authors.forename: Shu-Chien
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Surgery, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (S.C.H., Y.S.C.).
authors.forename: Yih-Sharng
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (S.N.C., J.K.W., M.H.W.).
authors.forename: Jou-Kou
authors.initials: JK
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (S.N.C., J.K.W., M.H.W.).
authors.forename: Mei-Hwan
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Department of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (C.T.T., L.Y.L., L.P.L., J.L.L.).
authors.forename: Ling-Ping
authors.initials: LP
authors.lastname: Lai
authors.affiliation: Department of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan (C.T.T., L.Y.L., L.P.L., J.L.L.).
authors.forename: Jiunn-Lee
authors.initials: JL
authors.lastname: Lin
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D018031:Connexin 43 / Q000032:analysis; D017630:Connexins / Q000032:analysis; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D006321:Heart / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology*; D007473:Ion Channels / Q000032:analysis; D009206:Myocardium / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D013771:Tetralogy of Fallot / Q000150:complications / Q000503:physiopathology / Q000601:surgery*; D000097003:Gap Junction alpha-5 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D007473:Ion Channels; D000097003:Gap Junction alpha-5 Protein
keywords: action potentials; connexin 43; ion channels; tachyarrhythmias; tetralogy of Fallot