Differential effect of anesthetics on mucociliary clearance in vivo in mice

Abstract 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...

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Autores principales:	Kyle S. Feldman, Eunwon Kim, Michael J. Czachowski, Yijen Wu, Cecilia W. Lo, Maliha Zahid
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9cb1cb17294a4c8f9374e89f293fce45
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spelling	oai:doaj.org-article:9cb1cb17294a4c8f9374e89f293fce452021-12-02T13:19:31ZDifferential effect of anesthetics on mucociliary clearance in vivo in mice10.1038/s41598-021-84605-y2045-2322https://doaj.org/article/9cb1cb17294a4c8f9374e89f293fce452021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84605-yhttps://doaj.org/toc/2045-2322Abstract 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 99mTc-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.Kyle S. FeldmanEunwon KimMichael J. CzachowskiYijen WuCecilia W. LoMaliha ZahidNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyle S. Feldman Eunwon Kim Michael J. Czachowski Yijen Wu Cecilia W. Lo Maliha Zahid Differential effect of anesthetics on mucociliary clearance in vivo in mice
description	Abstract 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 99mTc-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.
format	article
author	Kyle S. Feldman Eunwon Kim Michael J. Czachowski Yijen Wu Cecilia W. Lo Maliha Zahid
author_facet	Kyle S. Feldman Eunwon Kim Michael J. Czachowski Yijen Wu Cecilia W. Lo Maliha Zahid
author_sort	Kyle S. Feldman
title	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_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_sort	differential effect of anesthetics on mucociliary clearance in vivo in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9cb1cb17294a4c8f9374e89f293fce45
work_keys_str_mv	AT kylesfeldman differentialeffectofanestheticsonmucociliaryclearanceinvivoinmice AT eunwonkim differentialeffectofanestheticsonmucociliaryclearanceinvivoinmice AT michaeljczachowski differentialeffectofanestheticsonmucociliaryclearanceinvivoinmice AT yijenwu differentialeffectofanestheticsonmucociliaryclearanceinvivoinmice AT ceciliawlo differentialeffectofanestheticsonmucociliaryclearanceinvivoinmice AT malihazahid differentialeffectofanestheticsonmucociliaryclearanceinvivoinmice
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Differential effect of anesthetics on mucociliary clearance in vivo in mice

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