Irreversible electroporation (IRE) employs brief, high-electric field pulses to ablate tumors while preserving the extracellular matrix. Recently, we showed that combining short high-voltage (SHV) IRE pulses and long low-voltage (LLV) IRE pulses can enlarge the tissue ablation region, presumably through a synergistic effect. Objective: The goal of this study is to further investigate the effect of this combination on a 2-D cell layer tumor model. Methods: 2-D layers of tumor cells are exposed to various SHV and LLV combinations, and the results of propidium iodide (PI) and fluorescein diacetate staining are examined to correlate treatment protocols with the ensuing irreversible and reversible electroporation areas. Results: The combination of SHV+LLV pulses produces a larger area of electroporation and ablation than LLV+SHV pulses, LLV pulses alone, and SHV pulses alone. Conclusion: Judiciously combining SHV and LLV pulses can produce a synergistic effect that enlarges the electroporation-induced ablation area. A hypothetical explanation for this effect is that it involves a combination of pore expansion and electrolysis induced by LLV pulses in the area that had been reversibly permeabilized by the SHV pulses. Significance: This paper is valuable for the design of improved IRE protocols and provides a hypothesis for the mechanisms involved.

中文翻译：

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高电压和低电压不可逆电穿孔脉冲协同组合的二维细胞层研究

不可逆电穿孔 (IRE) 采用短暂的高电场脉冲来消融肿瘤，同时保留细胞外基质。最近，我们表明结合短高压 (SHV) IRE 脉冲和长低压 (LLV) IRE 脉冲可以扩大组织消融区域，大概是通过协同效应。目的：本研究的目的是进一步研究这种组合对二维细胞层肿瘤模型的影响。方法：将肿瘤细胞的二维层暴露于各种 SHV 和 LLV 组合，并检查碘化丙啶 (PI) 和荧光素二乙酸酯染色的结果，以将治疗方案与随后的不可逆和可逆电穿孔区域相关联。结果：SHV+LLV 脉冲的组合产生比 LLV+SHV 脉冲更大的电穿孔和消融区域，单独的 LLV 脉冲和单独的 SHV 脉冲。结论：明智地结合 SHV 和 LLV 脉冲可以产生协同效应，扩大电穿孔诱导的消融区域。对这种效应的一个假设解释是，它涉及由 LLV 脉冲在已被 SHV 脉冲可逆渗透的区域中引起的孔隙膨胀和电解的组合。意义：本文对于改进 IRE 协议的设计很有价值，并为所涉及的机制提供了一个假设。对这种效应的一个假设解释是，它涉及由 LLV 脉冲在已被 SHV 脉冲可逆渗透的区域中引起的孔隙膨胀和电解的组合。意义：本文对于改进 IRE 协议的设计很有价值，并为所涉及的机制提供了一个假设。对这种效应的一个假设解释是，它涉及由 LLV 脉冲在已被 SHV 脉冲可逆渗透的区域中引起的孔隙膨胀和电解的组合。意义：本文对于改进 IRE 协议的设计很有价值，并为所涉及的机制提供了一个假设。