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Assessing anesthetic activity through modulation of the membrane dipole potential
There is great individual variation in response to general anesthetics (GAs) leading to difficulties in optimal dosing and sometimes even accidental awareness during general anesthesia (AAGA). AAGA is a rare, but potentially devastating, complication affecting between 0.1% and 2% of patients undergo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625120/ https://www.ncbi.nlm.nih.gov/pubmed/28818873 http://dx.doi.org/10.1194/jlr.M073932 |
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author | Davis, Benjamin Michael Brenton, Jonathan Davis, Sterenn Shamsher, Ehtesham Sisa, Claudia Grgic, Ljuban Cordeiro, M. Francesca |
author_facet | Davis, Benjamin Michael Brenton, Jonathan Davis, Sterenn Shamsher, Ehtesham Sisa, Claudia Grgic, Ljuban Cordeiro, M. Francesca |
author_sort | Davis, Benjamin Michael |
collection | PubMed |
description | There is great individual variation in response to general anesthetics (GAs) leading to difficulties in optimal dosing and sometimes even accidental awareness during general anesthesia (AAGA). AAGA is a rare, but potentially devastating, complication affecting between 0.1% and 2% of patients undergoing surgery. The development of novel personalized screening techniques to accurately predict a patient’s response to GAs and the risk of AAGA remains an unmet clinical need. In the present study, we demonstrate the principle of using a fluorescent reporter of the membrane dipole potential, di-8-ANEPPs, as a novel method to monitor anesthetic activity using a well-described inducer/noninducer pair. The membrane dipole potential has previously been suggested to contribute a novel mechanism of anesthetic action. We show that the fluorescence ratio of di-8-ANEPPs changed in response to physiological concentrations of the anesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F(3)), but not the structurally similar noninducer, 1,2-dichlorohexafluorocyclobutane (F(6)), to artificial membranes and in vitro retinal cell systems. Modulation of the membrane dipole provides an explanation to overcome the limitations associated with the alternative membrane-mediated mechanisms of GA action. Furthermore, by combining this technique with noninvasive retinal imaging technologies, we propose that this technique could provide a novel and noninvasive technique to monitor GA susceptibility and identify patients at risk of AAGA. |
format | Online Article Text |
id | pubmed-5625120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-56251202017-10-04 Assessing anesthetic activity through modulation of the membrane dipole potential Davis, Benjamin Michael Brenton, Jonathan Davis, Sterenn Shamsher, Ehtesham Sisa, Claudia Grgic, Ljuban Cordeiro, M. Francesca J Lipid Res Research Articles There is great individual variation in response to general anesthetics (GAs) leading to difficulties in optimal dosing and sometimes even accidental awareness during general anesthesia (AAGA). AAGA is a rare, but potentially devastating, complication affecting between 0.1% and 2% of patients undergoing surgery. The development of novel personalized screening techniques to accurately predict a patient’s response to GAs and the risk of AAGA remains an unmet clinical need. In the present study, we demonstrate the principle of using a fluorescent reporter of the membrane dipole potential, di-8-ANEPPs, as a novel method to monitor anesthetic activity using a well-described inducer/noninducer pair. The membrane dipole potential has previously been suggested to contribute a novel mechanism of anesthetic action. We show that the fluorescence ratio of di-8-ANEPPs changed in response to physiological concentrations of the anesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F(3)), but not the structurally similar noninducer, 1,2-dichlorohexafluorocyclobutane (F(6)), to artificial membranes and in vitro retinal cell systems. Modulation of the membrane dipole provides an explanation to overcome the limitations associated with the alternative membrane-mediated mechanisms of GA action. Furthermore, by combining this technique with noninvasive retinal imaging technologies, we propose that this technique could provide a novel and noninvasive technique to monitor GA susceptibility and identify patients at risk of AAGA. The American Society for Biochemistry and Molecular Biology 2017-10 2017-08-17 /pmc/articles/PMC5625120/ /pubmed/28818873 http://dx.doi.org/10.1194/jlr.M073932 Text en Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc. http://creativecommons.org/licenses/by/4.0/ Author’s Choice—Final version free via Creative Commons CC-BY license. |
spellingShingle | Research Articles Davis, Benjamin Michael Brenton, Jonathan Davis, Sterenn Shamsher, Ehtesham Sisa, Claudia Grgic, Ljuban Cordeiro, M. Francesca Assessing anesthetic activity through modulation of the membrane dipole potential |
title | Assessing anesthetic activity through modulation of the membrane dipole potential |
title_full | Assessing anesthetic activity through modulation of the membrane dipole potential |
title_fullStr | Assessing anesthetic activity through modulation of the membrane dipole potential |
title_full_unstemmed | Assessing anesthetic activity through modulation of the membrane dipole potential |
title_short | Assessing anesthetic activity through modulation of the membrane dipole potential |
title_sort | assessing anesthetic activity through modulation of the membrane dipole potential |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625120/ https://www.ncbi.nlm.nih.gov/pubmed/28818873 http://dx.doi.org/10.1194/jlr.M073932 |
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