Kim Vitalii, Gudvangen Emily, Kondratiev Oleg, Redondo Luis, Xiao Shu, Pakhomov Andrei G
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
Energy Pulse Systems, 1600-546 Lisbon, Portugal.
Int J Mol Sci. 2021 Jun 30;22(13):7051. doi: 10.3390/ijms22137051.
Intense pulsed electric fields (PEF) are a novel modality for the efficient and targeted ablation of tumors by electroporation. The major adverse side effects of PEF therapies are strong involuntary muscle contractions and pain. Nanosecond-range PEF (nsPEF) are less efficient at neurostimulation and can be employed to minimize such side effects. We quantified the impact of the electrode configuration, PEF strength (up to 20 kV/cm), repetition rate (up to 3 MHz), bi- and triphasic pulse shapes, and pulse duration (down to 10 ns) on eliciting compound action potentials (CAPs) in nerve fibers. The excitation thresholds for single unipolar but not bipolar stimuli followed the classic strength-duration dependence. The addition of the opposite polarity phase for nsPEF increased the excitation threshold, with symmetrical bipolar nsPEF being the least efficient. Stimulation by nsPEF bursts decreased the excitation threshold as a power function above a critical duty cycle of 0.1%. The threshold reduction was much weaker for symmetrical bipolar nsPEF. Supramaximal stimulation by high-rate nsPEF bursts elicited only a single CAP as long as the burst duration did not exceed the nerve refractory period. Such brief bursts of bipolar nsPEF could be the best choice to minimize neuromuscular stimulation in ablation therapies.
强脉冲电场（PEF）是一种通过电穿孔有效且靶向消融肿瘤的新方法。PEF疗法的主要不良副作用是强烈的非自主肌肉收缩和疼痛。纳秒级PEF（nsPEF）在神经刺激方面效率较低，可用于将此类副作用降至最低。我们量化了电极配置、PEF强度（高达20 kV/cm）、重复频率（高达3 MHz）、双相和三相脉冲形状以及脉冲持续时间（低至10 ns）对神经纤维中复合动作电位（CAP）诱发的影响。单极而非双极刺激的兴奋阈值遵循经典的强度-时间依赖性。nsPEF添加相反极性相可提高兴奋阈值，对称双极nsPEF效率最低。nsPEF脉冲串刺激在高于0.1%的临界占空比时，作为幂函数降低兴奋阈值。对称双极nsPEF的阈值降低要弱得多。只要脉冲串持续时间不超过神经不应期，高速nsPEF脉冲串的超强刺激仅诱发单个CAP。这种双极nsPEF的短暂脉冲串可能是消融治疗中使神经肌肉刺激最小化的最佳选择。
