Rubinsky Liel, Guenther Enric, Mikus Paul, Stehling Michael, Rubinsky Boris
Interscience, Luzern, Switzerland.
Interscience, Luzern, Switzerland Boston University School of Medicine, MA, USA
Technol Cancer Res Treat. 2016 Oct;15(5):NP95-NP103. doi: 10.1177/1533034615601549. Epub 2015 Aug 31.
Nonthermal irreversible electroporation is a new tissue ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible electroporation is of interest because it allows treatment near sensitive tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with electroporation pulses to augment and optimize tissue ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that tissue ablation ascribed in the past to irreversible electroporation is actually caused by at least 3 different cytotoxic effects: irreversible electroporation without electrolysis, irreversible electroporation combined with electrolysis, and reversible electroporation combined with electrolysis. These different mechanisms may affect cell and tissue ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible electroporation studies in tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal electroporation ablation protocols.
非热不可逆电穿孔是一种新的组织消融技术，该技术通过在细胞上施加脉冲电场，在细胞膜上造成永久性损伤，从而诱导细胞死亡。非热不可逆电穿孔技术备受关注，因为它能够在血管和神经等敏感组织结构附近进行治疗。最近的两篇文章报道，电极处的电解反应产物可与电穿孔脉冲相结合，以增强和优化组织消融效果。这些文章引发了人们的担忧，即早期关于非热不可逆电穿孔的研究结果可能受到未被考虑的电解效应的影响。本研究的目的是在这些文章的背景下重新审视先前关于非热不可逆电穿孔的研究。研究表明，早期一些关于非热不可逆电穿孔的研究结果受到了未被考虑的电解作用的影响，特别是在比色皿中对细胞进行的研究。研究还表明，过去归因于不可逆电穿孔的组织消融实际上是由至少3种不同的细胞毒性效应引起的：无电解的不可逆电穿孔、与电解相结合的不可逆电穿孔以及与电解相结合的可逆电穿孔。这些不同的机制可能以不同的方式影响细胞和组织消融，其影响可能取决于各种临床参数，如电极的极性、输送的电荷量（电压、脉冲数量和长度）以及靶组织与电极的距离。目前的临床方案采用的电穿孔脉冲数量不断增加，现已比我们最初在组织中进行的基础非热不可逆电穿孔研究中使用的脉冲数量大一个数量级。细胞死亡的不同机制以及临床参数对这些机制的影响，可能解释了不同临床研究结果之间的差异，在设计最佳电穿孔消融方案时应予以考虑。
