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How to alleviate cardiac injury from electric shocks at the cellular level

Electric shocks, the only effective therapy for ventricular fibrillation, also electroporate cardiac cells and contribute to the high-mortality post-cardiac arrest syndrome. Copolymers such as Poloxamer 188 (P188) are known to preserve the membrane integrity and viability of electroporated cells, bu...

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Autores principales: Sowa, Pamela W., Kiełbik, Aleksander S., Pakhomov, Andrei G., Gudvangen, Emily, Mangalanathan, Uma, Adams, Volker, Pakhomova, Olga N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812960/
https://www.ncbi.nlm.nih.gov/pubmed/36620647
http://dx.doi.org/10.3389/fcvm.2022.1004024
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author Sowa, Pamela W.
Kiełbik, Aleksander S.
Pakhomov, Andrei G.
Gudvangen, Emily
Mangalanathan, Uma
Adams, Volker
Pakhomova, Olga N.
author_facet Sowa, Pamela W.
Kiełbik, Aleksander S.
Pakhomov, Andrei G.
Gudvangen, Emily
Mangalanathan, Uma
Adams, Volker
Pakhomova, Olga N.
author_sort Sowa, Pamela W.
collection PubMed
description Electric shocks, the only effective therapy for ventricular fibrillation, also electroporate cardiac cells and contribute to the high-mortality post-cardiac arrest syndrome. Copolymers such as Poloxamer 188 (P188) are known to preserve the membrane integrity and viability of electroporated cells, but their utility against cardiac injury from cardiopulmonary resuscitation (CPR) remains to be established. We studied the time course of cell killing, mechanisms of cell death, and protection with P188 in AC16 human cardiomyocytes exposed to micro- or nanosecond pulsed electric field (μsPEF and nsPEF) shocks. A 3D printer was customized with an electrode holder to precisely position electrodes orthogonal to a cell monolayer in a nanofiber multiwell plate. Trains of nsPEF shocks (200, 300-ns pulses at 1.74 kV) or μsPEF shocks (20, 100-μs pulses at 300 V) produced a non-uniform electric field enabling efficient measurements of the lethal effect in a wide range of the electric field strength. Cell viability and caspase 3/7 expression were measured by fluorescent microscopy 2–24 h after the treatment. nsPEF shocks caused little or no caspase 3/7 activation; most of the lethally injured cells were permeable to propidium dye already at 2 h after the exposure. In contrast, μsPEF shocks caused strong activation of caspase 3/7 at 2 h and the number of dead cells grew up to 24 h, indicating the prevalence of the apoptotic death pathway. P188 at 0.2–1% reduced cell death, suggesting its potential utility in vivo to alleviate electric injury from defibrillation.
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spelling pubmed-98129602023-01-06 How to alleviate cardiac injury from electric shocks at the cellular level Sowa, Pamela W. Kiełbik, Aleksander S. Pakhomov, Andrei G. Gudvangen, Emily Mangalanathan, Uma Adams, Volker Pakhomova, Olga N. Front Cardiovasc Med Cardiovascular Medicine Electric shocks, the only effective therapy for ventricular fibrillation, also electroporate cardiac cells and contribute to the high-mortality post-cardiac arrest syndrome. Copolymers such as Poloxamer 188 (P188) are known to preserve the membrane integrity and viability of electroporated cells, but their utility against cardiac injury from cardiopulmonary resuscitation (CPR) remains to be established. We studied the time course of cell killing, mechanisms of cell death, and protection with P188 in AC16 human cardiomyocytes exposed to micro- or nanosecond pulsed electric field (μsPEF and nsPEF) shocks. A 3D printer was customized with an electrode holder to precisely position electrodes orthogonal to a cell monolayer in a nanofiber multiwell plate. Trains of nsPEF shocks (200, 300-ns pulses at 1.74 kV) or μsPEF shocks (20, 100-μs pulses at 300 V) produced a non-uniform electric field enabling efficient measurements of the lethal effect in a wide range of the electric field strength. Cell viability and caspase 3/7 expression were measured by fluorescent microscopy 2–24 h after the treatment. nsPEF shocks caused little or no caspase 3/7 activation; most of the lethally injured cells were permeable to propidium dye already at 2 h after the exposure. In contrast, μsPEF shocks caused strong activation of caspase 3/7 at 2 h and the number of dead cells grew up to 24 h, indicating the prevalence of the apoptotic death pathway. P188 at 0.2–1% reduced cell death, suggesting its potential utility in vivo to alleviate electric injury from defibrillation. Frontiers Media S.A. 2022-12-22 /pmc/articles/PMC9812960/ /pubmed/36620647 http://dx.doi.org/10.3389/fcvm.2022.1004024 Text en Copyright © 2022 Sowa, Kiełbik, Pakhomov, Gudvangen, Mangalanathan, Adams and Pakhomova. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Sowa, Pamela W.
Kiełbik, Aleksander S.
Pakhomov, Andrei G.
Gudvangen, Emily
Mangalanathan, Uma
Adams, Volker
Pakhomova, Olga N.
How to alleviate cardiac injury from electric shocks at the cellular level
title How to alleviate cardiac injury from electric shocks at the cellular level
title_full How to alleviate cardiac injury from electric shocks at the cellular level
title_fullStr How to alleviate cardiac injury from electric shocks at the cellular level
title_full_unstemmed How to alleviate cardiac injury from electric shocks at the cellular level
title_short How to alleviate cardiac injury from electric shocks at the cellular level
title_sort how to alleviate cardiac injury from electric shocks at the cellular level
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812960/
https://www.ncbi.nlm.nih.gov/pubmed/36620647
http://dx.doi.org/10.3389/fcvm.2022.1004024
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