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. 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 KC h IP 2 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.