Sowa Pamela W, Novickij Vitalij, Kiełbik Aleksander, Kollotzek Ferdinand, Heinzmann David, Borst Oliver, Gawaz Meinrad P
Department of Cardiology and Angiology, University Hospital Tübingen, Tübingen, Germany.
Institute of High Magnetic Fields, Vilnius Gediminas Technical University, Vilnius, Lithuania; Department of Immunology and Bioelectrochemistry, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
Heart Rhythm. 2025 Sep;22(9):e697-e709. doi: 10.1016/j.hrthm.2025.03.1954. Epub 2025 Mar 17.
Nanosecond pulsed electric fields (nsPEFs) are a promising method for cardiac pulsed field ablation, currently in early clinical trials. However, effective ablation often requires high voltages, more pulses, and higher frequencies, which can raise tissue temperatures because of Joule heating. Fractionated pulse delivery can help mitigate thermal effects and potentially evoke electrosensitization, increasing cell damage.
This study evaluates the effects of fractionated nsPEF on treatment efficacy and its selectivity against cardiomyocytes, aiming to determine whether fractionation improves ablation outcomes.
Monolayers of HL-1 murine cardiomyocytes, MHEC5-T murine endothelial cells, AC16 human cardiomyocytes, and human umbilical vein endothelial cells were exposed to pulsed electric fields using a contact electrode operated by a custom robotic system. Cell viability and permeability were measured using wide-field fluorescence microscopy. Stained areas were matched to simulated electric fields for dose-response curves. Fractionation effects were also validated in an ex vivo murine model.
Fractionation of nsPEF reduced the electric field affecting 50% of cells for plasma membrane permeabilization by 10% compared with a single train of 200 pulses (P < .0001). This translated into enhanced cardiomyocyte ablation, with fractionated exposure lowering the electric field affecting 50% of cells for cell killing by 13% (P < .0001). Ex vivo results further confirmed a larger ablation area with fractionated nsPEF (P < .0001).
Fractionated nsPEF improves cardiac ablation efficiency by enhancing membrane permeability and cell-killing effect. These findings suggest that fractionated delivery could optimize nsPEF therapies, offering a more effective approach for cardiac ablation.
纳秒级脉冲电场（nsPEF）是一种用于心脏脉冲场消融的有前景的方法，目前正处于早期临床试验阶段。然而，有效的消融通常需要高电压、更多脉冲和更高频率，这会因焦耳热而升高组织温度。分次脉冲递送有助于减轻热效应，并可能引发电敏化，增加细胞损伤。
本研究评估分次nsPEF对治疗效果的影响及其对心肌细胞的选择性，旨在确定分次递送是否能改善消融结果。
使用由定制机器人系统操作的接触电极，将HL-1小鼠心肌细胞、MHEC5-T小鼠内皮细胞、AC16人心肌细胞和人脐静脉内皮细胞单层暴露于脉冲电场。使用宽场荧光显微镜测量细胞活力和通透性。将染色区域与模拟电场匹配以绘制剂量反应曲线。还在离体小鼠模型中验证了分次递送的效果。
与单次200个脉冲序列相比，nsPEF的分次递送使影响50%细胞膜通透化细胞的电场降低了10%（P <.0001）。这转化为增强的心肌细胞消融，分次暴露使影响50%细胞杀伤的电场降低了13%（P <.0001）。离体结果进一步证实分次nsPEF具有更大的消融面积（P <.0001）。
分次nsPEF通过增强膜通透性和细胞杀伤作用提高了心脏消融效率。这些发现表明，分次递送可以优化nsPEF治疗，为心脏消融提供一种更有效的方法。
