A Conceivable Mechanism Responsible for the Synergy of High and Low Voltage Irreversible Electroporation Pulses
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Annals of Biomedical Engineering (Ó 2019) https://doi.org/10.1007/s10439-019-02258-5
A Conceivable Mechanism Responsible for the Synergy of High and Low Voltage Irreversible Electroporation Pulses YANPENG LV,1,2 CHENGUO YAO ,1 and BORIS RUBINSKY2 1
College of Electrical Engineering, Chongqing University, Chongqing 400030, China; and 2Department of Mechanical Engineering and Department of Bioengineering, University of California Berkeley, Berkeley, CA 94720, USA (Received 21 September 2018; accepted 29 March 2019) Associate Editor Stefan M. Duma oversaw the review of this article.
Abstract—Irreversible electroporation (IRE), is a new nonthermal tissue ablation technology in which brief high electric field pulses are delivered across the target tissue to induce cell death by irreversible permeabilization of the cell membrane. A deficiency of conventional IRE is that the ablation zone is relatively small, bounded by the irreversible electroporation isoelectric field margin. In the previous studies we have introduced a new treatment protocol that combines few short high voltage (SHV) pulses with long low-voltage (LLV) pulses. In the previous studies, we also have shown that the addition of few SHV pulses increases by almost a factor of two the area ablated by a protocol that employs only the LLV pulses. This study employs potato and gel phantom to generate a plausible explanation for the mechanism. The study provides circumstantial evidence that the mechanism involved is the production of electrolytic compounds by the LLV pulse sequence, which causes tissue ablation beyond the margin of the irreversible electroporation isoelectric field generated by the SHV pulses, presumable to the reversible electroporation isoelectric field margin generated by the SHV pulses. Keywords—Focal ablation, Electroporation, Electrolysis, High and low voltage pulses, Synergistic effect.
INTRODUCTION Electroporation, is the permeabilization of the cell membrane with brief, high electric fields, delivered across the cell.14 Currently, electroporation is used for tissue ablation, through two modalities, electrochemotherapy9,23 and irreversible electroporation.7,10,27 These modalities are defined by the electric parameters used for the cell membrane permeabilization. The primary electric parameters are the electric
Address correspondence to Chenguo Yao, College of Electrical Engineering, Chongqing University, Chongqing 400030, China. Electronic mail: [email protected]
field and the time-based mode of delivery of the electric field. Electrochemotherapy employs reversible electroporation (RE), in which the electric parameters cause transient permeabilization of the cell membrane, after which the cell membrane reseals. Combining reversible electroporation with injection of toxic chemical additives such as bleomycin or cis-platinum, that penetrate the cell during the temporary permeabilization of the cell membrane, is electrochemotherapy (EChT). Other electric parameters, in particular higher electric fields and longer times of delivery can cause i
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