Repolarization Alternans and Ventricular Arrhythmia in a Repaired Tetralogy of Fallot Animal Model
Repolarization Alternans and Ventricular Arrhythmia in a Repaired Tetralogy of Fallot Animal Model
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DOI：
10.1161/jaha.115.002173
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发表时间：
2015-12-01
影响因子：
5.4
通讯作者：
Lin, Jiunn-Lee
中科院分区：
文献类型：
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作者：
Chiu, Shuenn-Nan;Tsai, Chia-Ti;Lin, Jiunn-Lee
背景：室性心律失常是修复性法洛四联症（rTOF）患者晚期死亡的重要原因。通过犬rTOF模型，研究了复极化交替的作用及其电生理机制。方法与结果：6只狗接受右心室流出道（RVOT）经环贴片、肺动脉瓣破坏和右束支消融模拟rTOF。1年后，我们进行了高分辨率双电压和钙光学测绘，记录了切除的右心室流出道楔形的动作电位和钙瞬态。另外6只未做手术的狗作为对照组。与对照组相比，rTOF组更容易发生动作电位持续交替（APD-ALT）和空间不协调APD-ALT （APD-ALT阈值：516 +/- 36 vs 343 +/- 36 ms， P=0.017； APD-ALT不协调阈值：387 +/- 30 vs 310 +/- 14 ms， P=0.046）。我们在rTOF组检测到2次室性心动过速，但在对照组中没有。rTOF组Kv4.3和KChIP2表达降低。rTOF组连接蛋白43的表达也降低，传导速度相应降低，这可能是APD-ALT在空间上不一致的原因。我们还发现RVOT具有明显的电生理特征，包括APD- alt的大小与起搏周期长度之间的双相关系，APD- alt的解耦和钙瞬态交替，以及rTOF中APD缩短但未改变的APD恢复。结论：我们展示了RVOT新的电生理特性。在rTOF模型中，RVOT对时间和空间不一致的APD-ALT表现出增加的敏感性，而APD-ALT并不完全依赖于钙瞬态交替。
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.