Department of Physics, School of Physical Science and Technology, Ningbo University, Zhejiang, China (Z.Z.).
Department of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA (P.-S.C.).
Circ Arrhythm Electrophysiol. 2022 Jan;15(1):e010365. doi: 10.1161/CIRCEP.121.010365. Epub 2021 Dec 29.
Three types of characteristic ST-segment elevation are associated with Brugada syndrome but only type 1 is diagnostic. Why only type 1 ECG is diagnostic remains unanswered.
Computer simulations were performed in single cells, 1-dimensional cables, and 2-dimensional tissues to investigate the effects of the peak and late components of the transient outward potassium current (I), sodium current, and L-type calcium current (I) as well as other potassium currents on the genesis of ECG morphologies and phase 2 reentry (P2R).
Although a sufficiently large peak I was required to result in the type 1 ECG pattern and P2R, increasing the late component of I converted type 1 ECG to type 2 ECG and suppressed P2R. Increasing the peak I promoted spiral wave breakup, potentiating the transition from tachycardia to fibrillation, but increasing the late I prevented spiral wave breakup by flattening the action potential duration restitution and preventing P2R. A sufficiently large I conductance was needed for P2R to occur, but once above the critical conductance, blocking I promoted P2R. However, selectively blocking the window and late components of I suppressed P2R, countering the effect of the late I. Blocking either the peak or late components of sodium current promoted P2R, with the late sodium current blockade having the larger effect. As expected, increasing other potassium currents potentiated P2R, with ATP-sensitive potassium current exhibiting a larger effect than rapid and slow component of the delayed rectifier potassium current.
The peak I promotes type 1 ECG and P2R, whereas the late I converts type 1 ECG to type 2 ECG and suppresses P2R. Blocking the peak I and either the peak or the late sodium current promotes P2R, whereas blocking the window and late I suppresses P2R. These results provide important insights into the mechanisms of arrhythmogenesis and potential therapeutic targets for treatment of Brugada syndrome. Graphic Abstract: A graphic abstract is available for this article.
Brugada 综合征与三种特征性的 ST 段抬高有关，但只有 1 型具有诊断意义。为什么只有 1 型心电图具有诊断意义，目前仍未得到解答。
在单细胞、1 维电缆和 2 维组织中进行计算机模拟，以研究瞬时外向钾电流（I）、钠电流和 L 型钙电流（I）的峰值和晚期成分以及其他钾电流对心电图形态和 2 相折返（P2R）的发生的影响。
尽管需要足够大的峰值 I 才能导致 1 型心电图模式和 P2R，但增加 I 的晚期成分会将 1 型心电图转换为 2 型心电图并抑制 P2R。增加峰值 I 会促进螺旋波破裂，增强从心动过速到颤动的转变，但增加晚期 I 会通过使动作电位时程恢复平坦并防止 P2R 来防止螺旋波破裂。发生 P2R 需要足够大的 I 电导，但一旦超过临界电导，阻断 I 会促进 P2R。然而，选择性阻断 I 的窗口和晚期成分会抑制 P2R，抵消晚期 I 的作用。阻断钠电流的峰值或晚期成分都会促进 P2R，其中晚期钠电流阻断的影响更大。正如预期的那样，增加其他钾电流会增强 P2R，其中 ATP 敏感性钾电流的作用大于快速和缓慢延迟整流钾电流的作用。
峰值 I 促进 1 型心电图和 P2R，而晚期 I 将 1 型心电图转换为 2 型心电图并抑制 P2R。阻断峰值 I 和峰值或晚期钠电流中的任何一个都会促进 P2R，而阻断窗口和晚期 I 会抑制 P2R。这些结果为心律失常发生的机制提供了重要的见解，并为 Brugada 综合征的治疗提供了潜在的治疗靶点。
