The Role of pH Fronts in Reversible Electroporation

Pablo Turjanski,Fernando Victor Molina,Sebastian Michinski,Nahuel Olaiz,Guillermo Marshall,Felipe Maglietti,Cecilia Suárez,Boris Rubinsky

doi:10.1371/journal.pone.0017303

Pablo Turjanski, Fernando Victor Molina + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0017303

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Abstract

We present experimental measurements and theoretical predictions of ion transport in agar gels during reversible electroporation (ECT) for conditions typical to many clinical studies found in the literature, revealing the presence of pH fronts emerging from both electrodes. These results suggest that pH fronts are immediate and substantial. Since they might give rise to tissue necrosis, an unwanted condition in clinical applications of ECT as well as in irreversible electroporation (IRE) and in electrogenetherapy (EGT), it is important to quantify their extent and evolution. Here, a tracking technique is used to follow the space-time evolution of these pH fronts. It is found that they scale in time as , characteristic of a predominantly diffusive process. Comparing ECT pH fronts with those arising in electrotherapy (EChT), another treatment applying constant electric fields whose main goal is tissue necrosis, a striking result is observed: anodic acidification is larger in ECT than in EChT, suggesting that tissue necrosis could also be greater. Ways to minimize these adverse effects in ECT are suggested.

Highlights

During the last decade, pulsed electric fields were explored in local tumor treatment based upon electroporation, a technique in which pulsed electric fields are employed to disturb cell membrane integrity creating pores across it
In this paper we look into the electroporation process from a new angle apparently overseen in the literature, the role of pH in ECT modeling based on ion transport and associated pH changes that take place during the treatment
Acid and basic pH fronts are represented by pink and red pixels, respectively. This figure is constructed from a stack of pH spatial distributions for different times, and unveils the existence of significant pH gradients during a typical ECT. It is readily seen the larger extension of the anodic pH front relative to the cathodic one, though both pH indicators change color at the same distance from neutrality (6.2 and 8.3 for acid and basic indicators respectively)

Summary

Introduction

During the last decade, pulsed electric fields were explored in local tumor treatment based upon electroporation, a technique in which pulsed electric fields are employed to disturb cell membrane integrity creating pores across it.

Results

Conclusion