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Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro

Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with oth...

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Autores principales: Baena-Montes, Jara M., O’Halloran, Tony, Clarke, Cormac, Donaghey, Kevin, Dunne, Eoghan, O’Halloran, Martin, Quinlan, Leo R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409892/
https://www.ncbi.nlm.nih.gov/pubmed/36005404
http://dx.doi.org/10.3390/jcdd9080240
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author Baena-Montes, Jara M.
O’Halloran, Tony
Clarke, Cormac
Donaghey, Kevin
Dunne, Eoghan
O’Halloran, Martin
Quinlan, Leo R.
author_facet Baena-Montes, Jara M.
O’Halloran, Tony
Clarke, Cormac
Donaghey, Kevin
Dunne, Eoghan
O’Halloran, Martin
Quinlan, Leo R.
author_sort Baena-Montes, Jara M.
collection PubMed
description Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy sources. However, more tissue and cell-specific evidence is required to demonstrate the selective threshold parameters for human cells. The aim here is to determine the optimal ablation threshold parameters related to lesion size for human cardiomyocytes in 2D culture. Conventional biphasic pulses of different field strengths and on-times were delivered in a monolayer culture system of human AC16 cardiomyocytes. The dynamics of cell death and lesion dimensions were examined at different time points. Human cardiomyocytes are susceptible to significant electroporation and cell death at a field strength of 750 V/cm or higher with 100 μs pulses. Increasing the IRE on-time from 3 ms to 60 ms reduces the effective field threshold to 250 V/cm. Using very short pulses of 2 μs and 5 μs also causes significant cell death, but only at fields higher than 1000 V/cm. A longer on-time results in more cell death and induced greater lesion area in 2D models. In addition, different forms of cell death are predicted based on the evolution of cell death over time. This study presents important findings on the ability of different IRE parameters to induce human cardiomyocyte cell death. Lesion size can be tuned by appropriate choice of IRE parameters and cardiomyocytes display an upregulation of delayed cell death 24 h after electroporation, which is an important consideration for clinical practice.
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spelling pubmed-94098922022-08-26 Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro Baena-Montes, Jara M. O’Halloran, Tony Clarke, Cormac Donaghey, Kevin Dunne, Eoghan O’Halloran, Martin Quinlan, Leo R. J Cardiovasc Dev Dis Article Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy sources. However, more tissue and cell-specific evidence is required to demonstrate the selective threshold parameters for human cells. The aim here is to determine the optimal ablation threshold parameters related to lesion size for human cardiomyocytes in 2D culture. Conventional biphasic pulses of different field strengths and on-times were delivered in a monolayer culture system of human AC16 cardiomyocytes. The dynamics of cell death and lesion dimensions were examined at different time points. Human cardiomyocytes are susceptible to significant electroporation and cell death at a field strength of 750 V/cm or higher with 100 μs pulses. Increasing the IRE on-time from 3 ms to 60 ms reduces the effective field threshold to 250 V/cm. Using very short pulses of 2 μs and 5 μs also causes significant cell death, but only at fields higher than 1000 V/cm. A longer on-time results in more cell death and induced greater lesion area in 2D models. In addition, different forms of cell death are predicted based on the evolution of cell death over time. This study presents important findings on the ability of different IRE parameters to induce human cardiomyocyte cell death. Lesion size can be tuned by appropriate choice of IRE parameters and cardiomyocytes display an upregulation of delayed cell death 24 h after electroporation, which is an important consideration for clinical practice. MDPI 2022-07-28 /pmc/articles/PMC9409892/ /pubmed/36005404 http://dx.doi.org/10.3390/jcdd9080240 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Baena-Montes, Jara M.
O’Halloran, Tony
Clarke, Cormac
Donaghey, Kevin
Dunne, Eoghan
O’Halloran, Martin
Quinlan, Leo R.
Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro
title Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro
title_full Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro
title_fullStr Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro
title_full_unstemmed Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro
title_short Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro
title_sort electroporation parameters for human cardiomyocyte ablation in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409892/
https://www.ncbi.nlm.nih.gov/pubmed/36005404
http://dx.doi.org/10.3390/jcdd9080240
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