Speaker
Description
Pulsed field ablation (PFA) – an electroporation-based ablation - is being rapidly adopted as a safer and more efficient alternative to conventional thermal ablation methods for the treatment of cardiac arrhythmias, particularly atrial fibrillation. Although electroporation is a phenomenon occurring on the cell membrane level, its effects require modeling on several levels. The basic biophysics of PFA, focusing on electroporation at the membrane, cellular, and tissue levels will be presented providing mechanistic explanations for the observed clinical outcomes and potential adverse events. Drawing on decades of electroporation research in other biomedical fields, modeling attempts/efforts will challenge current understanding of PFA. Cell membrane electroporation is based on long standing “pore formation” theory leading to transient membrane permeabilization \cite{Kotnik_Rems_Tarek_Miklavcic_2019}. Although non-thermal, when applied in vivo, high electric currents increase temperature, which can be significant \cite{Cornelis_Cindric_Kos_Fujimori_Petre_Miklavcic_Solomon_Srimathveeravalli_2020}. Cell membrane electroporation is usually related to membrane electroporation which depends on local electric field. Electric field distribution in the tissue depends on tissue conductivity, which is inhomogeneous and anisotropic, and further increases locally with cell membrane electroporation and temperature increase. Mass transport, electrochemistry and cellular and tissue effects like cell death \cite{Batista Napotnik_Polajzer_Miklavcic_2021}, interstitial fluid pressure \cite{Pusenjak_Miklavcic_2000} and effects on blood perfusion \cite{Jarm_Cemazar_Miklavcic_Sersa_2010} are only sparsely addressed although they may be critical in predicting treatment outcome.
Bibliography
@article{Kotnik_Rems_Tarek_Miklavcic_2019, title={Membrane Electroporation and Electropermeabilization: Mechanisms and Models}, volume={48}, ISSN={1936-122X, 1936-1238}, url={https://www.annualreviews.org/doi/10.1146/annurev-biophys-052118-115451}, DOI={10.1146/annurev-biophys-052118-115451}, abstractNote={Exposure of biological cells to high-voltage, short-duration electric pulses causes a transient increase in their plasma membrane permeability, allowing transmembrane transport of otherwise impermeant molecules. In recent years, large steps were made in the understanding of underlying events. Formation of aqueous pores in the lipid bilayer is now a widely recognized mechanism, but evidence is growing that changes to individual membrane lipids and proteins also contribute, substantiating the need for terminological distinction between electroporation and electropermeabilization. We first revisit experimental evidence for electrically induced membrane permeability, its correlation with transmembrane voltage, and continuum models of electropermeabilization that disregard the molecular-level structure and events. We then present insights from molecular-level modeling, particularly atomistic simulations that enhance understanding of pore formation, and evidence of chemical modifications of membrane lipids and functional modulation of membrane proteins affecting membrane permeability. Finally, we discuss the remaining challenges to our full understanding of electroporation and electropermeabilization.}, number={1}, journal={Annual Review of Biophysics}, author={Kotnik, Tadej and Rems, Lea and Tarek, Mounir and Miklavčič, Damijan}, year={2019}, month=may, pages={63–91}, language={en} }
@article{Cornelis_Cindric_Kos_Fujimori_Petre_Miklavcic_Solomon_Srimathveeravalli_2020, title={Peri-tumoral Metallic Implants Reduce the Efficacy of Irreversible Electroporation for the Ablation of Colorectal Liver Metastases}, volume={43}, ISSN={0174-1551, 1432-086X}, url={http://link.springer.com/10.1007/s00270-019-02300-y}, DOI={10.1007/s00270-019-02300-y}, number={1}, journal={CardioVascular and Interventional Radiology}, author={Cornelis, Francois H. and Cindrič, Helena and Kos, Bor and Fujimori, Masashi and Petre, Elena N. and Miklavčič, Damijan and Solomon, Stephen B. and Srimathveeravalli, Govindarajan}, year={2020}, month=jan, pages={84–93}, language={en} }
@article{Batista Napotnik_Polajzer_Miklavcic_2021, title={Cell death due to electroporation – A review}, volume={141}, ISSN={15675394}, url={https://linkinghub.elsevier.com/retrieve/pii/S1567539421001341}, DOI={10.1016/j.bioelechem.2021.107871}, journal={Bioelectrochemistry}, author={Batista Napotnik, Tina and Polajžer, Tamara and Miklavčič, Damijan}, year={2021}, month=oct, pages={107871}, language={en} }
@article{Pusenjak_Miklavcic_2000, title={Modeling of interstitial fluid pressure in solid tumor}, volume={8}, rights={https://www.elsevier.com/tdm/userlicense/1.0/}, ISSN={09284869}, url={https://linkinghub.elsevier.com/retrieve/pii/S0928486900000033}, DOI={10.1016/S0928-4869(00)00003-3}, number={1–2}, journal={Simulation Practice and Theory}, author={Pusenjak, Jani and Miklavcic, Damijan}, year={2000}, month=apr, pages={17–24}, language={en} }
@article{Jarm_Cemazar_Miklavcic_Sersa_2010, title={Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases}, volume={10}, ISSN={1473-7140, 1744-8328}, url={http://www.tandfonline.com/doi/full/10.1586/era.10.43}, DOI={10.1586/era.10.43}, number={5}, journal={Expert Review of Anticancer Therapy}, author={Jarm, Tomaz and Cemazar, Maja and Miklavcic, Damijan and Sersa, Gregor}, year={2010}, month=may, pages={729–746}, language={en} }
