Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation
Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation
复制标题
使用高频电刺激的时空控制心脏传导阻滞
作者：
B. Dura;G. Kovacs;L. Giovangrandi
背景技术长期以来一直在寻求用于心脏兴奋的电抑制的方法来控制兴奋性和传导，但迄今为止仍然基本上不切实际。已知高振幅交流电 (AC) 刺激可延长心脏动作电位 (AP)，并且最近已被用于通过产生可逆传导阻滞来终止折返性心律失常。然而，相似频率的低振幅电流已被证明会通过产生重复的 AP 来夹带心脏组织，在某些情况下导致体内心室颤动和血流动力学崩溃。因此，非常需要一种不会导致夹带的抑制方法——无论刺激幅度如何（在体内环境中必然会波动）。方法/主要发现 我们使用正弦波和方波研究了更宽的振幅和频率范围对细胞外交流电刺激对微电极阵列上培养的 HL-1 心肌细胞的抑制作用的影响。我们的结果表明，在足够高的频率下，心脏组织对刺激幅度表现出二元响应，要么延长 AP，要么没有效果，从而有效地避免了在较低频率下观察到的重复放电夹带的风险。我们进一步证明了在跳动培养物中精确定义可逆局部传导阻滞而不影响非阻滞区域中的传播活动的能力。传导阻滞分别由电极几何形状和刺激持续时间进行时空控制，并且可持续较长的持续时间（300 秒）。结论/意义 对高频交流刺激引起的心脏兴奋的抑制表现出对高于阈值频率的幅度的二元响应，从而能够产生可逆传导阻滞，而没有夹带的风险。这种抑制方法可以为体外心律失常建模提供新的方法，并为体内心脏测绘和射频消融指导应用提供更安全、更有效的工具。
Background Methods for the electrical inhibition of cardiac excitation have long been sought to control excitability and conduction, but to date remain largely impractical. High-amplitude alternating current (AC) stimulation has been known to extend cardiac action potentials (APs), and has been recently exploited to terminate reentrant arrhythmias by producing reversible conduction blocks. Yet, low-amplitude currents at similar frequencies have been shown to entrain cardiac tissues by generation of repetitive APs, leading in some cases to ventricular fibrillation and hemodynamic collapse in vivo. Therefore, an inhibition method that does not lead to entrainment – irrespective of the stimulation amplitude (bound to fluctuate in an in vivo setting) – is highly desirable. Methodology/Principal Findings We investigated the effects of broader amplitude and frequency ranges on the inhibitory effects of extracellular AC stimulation on HL-1 cardiomyocytes cultured on microelectrode arrays, using both sinusoidal and square waveforms. Our results indicate that, at sufficiently high frequencies, cardiac tissue exhibits a binary response to stimulus amplitude with either prolonged APs or no effect, thereby effectively avoiding the risks of entrainment by repetitive firing observed at lower frequencies. We further demonstrate the ability to precisely define reversible local conduction blocks in beating cultures without influencing the propagation activity in non-blocked areas. The conduction blocks were spatiotemporally controlled by electrode geometry and stimuli duration, respectively, and sustainable for long durations (300 s). Conclusion/Significance Inhibition of cardiac excitation induced by high-frequency AC stimulation exhibits a binary response to amplitude above a threshold frequency, enabling the generation of reversible conduction blocks without the risks of entrainment. This inhibition method could yield novel approaches for arrhythmia modeling in vitro, as well as safer and more efficacious tools for in vivo cardiac mapping and radio-frequency ablation guidance applications.
DOI：
10.1073/pnas.95.6.2979
发表时间：
1998-03-17
影响因子：
11.1
作者：
Claycomb, WC;Lanson, NA;Izzo, NJ
通讯作者：
Izzo, NJ
影响因子：
64.8
作者：
Zhang, Feng;Wang, Li-Ping;Deisseroth, Karl
通讯作者：
Deisseroth, Karl