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Differential effect of anesthetics on mucociliary clearance in vivo in mice

Respiratory mucociliary clearance (MCC) is a key defense mechanism that functions to entrap and transport inhaled pollutants, particulates, and pathogens away from the lungs. Previous work has identified a number of anesthetics to have cilia depressive effects in vitro. Wild-type C57BL/6 J mice rece...

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Autores principales: Feldman, Kyle S., Kim, Eunwon, Czachowski, Michael J., Wu, Yijen, Lo, Cecilia W., Zahid, Maliha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921682/
https://www.ncbi.nlm.nih.gov/pubmed/33649513
http://dx.doi.org/10.1038/s41598-021-84605-y
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author Feldman, Kyle S.
Kim, Eunwon
Czachowski, Michael J.
Wu, Yijen
Lo, Cecilia W.
Zahid, Maliha
author_facet Feldman, Kyle S.
Kim, Eunwon
Czachowski, Michael J.
Wu, Yijen
Lo, Cecilia W.
Zahid, Maliha
author_sort Feldman, Kyle S.
collection PubMed
description Respiratory mucociliary clearance (MCC) is a key defense mechanism that functions to entrap and transport inhaled pollutants, particulates, and pathogens away from the lungs. Previous work has identified a number of anesthetics to have cilia depressive effects in vitro. Wild-type C57BL/6 J mice received intra-tracheal installation of (99m)Tc-Sulfur colloid, and were imaged using a dual-modality SPECT/CT system at 0 and 6 h to measure baseline MCC (n = 8). Mice were challenged for one hour with inhalational 1.5% isoflurane, or intraperitoneal ketamine (100 mg/kg)/xylazine (20 mg/kg), ketamine (0.5 mg/kg)/dexmedetomidine (50 mg/kg), fentanyl (0.2 mg/kg)/1.5% isoflurane, propofol (120 mg/Kg), or fentanyl/midazolam/dexmedetomidine (0.025 mg/kg/2.5 mg/kg/0.25 mg/kg) prior to MCC assessment. The baseline MCC was 6.4%, and was significantly reduced to 3.7% (p = 0.04) and 3.0% (p = 0.01) by ketamine/xylazine and ketamine/dexmedetomidine challenge respectively. Importantly, combinations of drugs containing fentanyl, and propofol in isolation did not significantly depress MCC. Although no change in cilia length or percent ciliation was expected, we tried to correlate ex-vivo tracheal cilia ciliary beat frequency and cilia-generated flow velocities with MCC and found no correlation. Our results indicate that anesthetics containing ketamine (ketamine/xylazine and ketamine/dexmedetomidine) significantly depress MCC, while combinations containing fentanyl (fentanyl/isoflurane, fentanyl/midazolam/dexmedetomidine) and propofol do not. Our method for assessing MCC is reproducible and has utility for studying the effects of other drug combinations.
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spelling pubmed-79216822021-03-02 Differential effect of anesthetics on mucociliary clearance in vivo in mice Feldman, Kyle S. Kim, Eunwon Czachowski, Michael J. Wu, Yijen Lo, Cecilia W. Zahid, Maliha Sci Rep Article Respiratory mucociliary clearance (MCC) is a key defense mechanism that functions to entrap and transport inhaled pollutants, particulates, and pathogens away from the lungs. Previous work has identified a number of anesthetics to have cilia depressive effects in vitro. Wild-type C57BL/6 J mice received intra-tracheal installation of (99m)Tc-Sulfur colloid, and were imaged using a dual-modality SPECT/CT system at 0 and 6 h to measure baseline MCC (n = 8). Mice were challenged for one hour with inhalational 1.5% isoflurane, or intraperitoneal ketamine (100 mg/kg)/xylazine (20 mg/kg), ketamine (0.5 mg/kg)/dexmedetomidine (50 mg/kg), fentanyl (0.2 mg/kg)/1.5% isoflurane, propofol (120 mg/Kg), or fentanyl/midazolam/dexmedetomidine (0.025 mg/kg/2.5 mg/kg/0.25 mg/kg) prior to MCC assessment. The baseline MCC was 6.4%, and was significantly reduced to 3.7% (p = 0.04) and 3.0% (p = 0.01) by ketamine/xylazine and ketamine/dexmedetomidine challenge respectively. Importantly, combinations of drugs containing fentanyl, and propofol in isolation did not significantly depress MCC. Although no change in cilia length or percent ciliation was expected, we tried to correlate ex-vivo tracheal cilia ciliary beat frequency and cilia-generated flow velocities with MCC and found no correlation. Our results indicate that anesthetics containing ketamine (ketamine/xylazine and ketamine/dexmedetomidine) significantly depress MCC, while combinations containing fentanyl (fentanyl/isoflurane, fentanyl/midazolam/dexmedetomidine) and propofol do not. Our method for assessing MCC is reproducible and has utility for studying the effects of other drug combinations. Nature Publishing Group UK 2021-03-01 /pmc/articles/PMC7921682/ /pubmed/33649513 http://dx.doi.org/10.1038/s41598-021-84605-y Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Feldman, Kyle S.
Kim, Eunwon
Czachowski, Michael J.
Wu, Yijen
Lo, Cecilia W.
Zahid, Maliha
Differential effect of anesthetics on mucociliary clearance in vivo in mice
title Differential effect of anesthetics on mucociliary clearance in vivo in mice
title_full Differential effect of anesthetics on mucociliary clearance in vivo in mice
title_fullStr Differential effect of anesthetics on mucociliary clearance in vivo in mice
title_full_unstemmed Differential effect of anesthetics on mucociliary clearance in vivo in mice
title_short Differential effect of anesthetics on mucociliary clearance in vivo in mice
title_sort differential effect of anesthetics on mucociliary clearance in vivo in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921682/
https://www.ncbi.nlm.nih.gov/pubmed/33649513
http://dx.doi.org/10.1038/s41598-021-84605-y
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