Repolarization alternans and ventricular arrhythmia in a repaired tetralogy of Fallot animal model

Shuenn Nan Chiu, Chia Ti Tsai, Lian Yu Lin, Shu Chien Huang, Yih Sharng Chen, Jou Kou Wang, Mei Hwan Wu, Ling Ping Lai, Jiunn Lee Lin

Research output: Contribution to journalArticle

7 Citations (Scopus)

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. Methods and 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.

Original languageEnglish
Article numbere002173
JournalJournal of the American Heart Association
Volume4
Issue number12
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

Keywords

  • Action potentials
  • Connexin 43
  • Ion channels
  • Tachyarrhythmias
  • Tetralogy of Fallot

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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