Resistance to state transitions in responsiveness is differentially modulated by different volatile anaesthetics in male mice.

Anesthetics, Inhalation / pharmacology Animals Halothane / pharmacology Isoflurane / pharmacology Male Mice Mice, Inbred C57BL Models, Animal Reflex, Righting / drug effects Sevoflurane / pharmacology
general anaesthesia individual-based pharmacology inhalational anaesthetics population-based pharmacology responsiveness state transitions

Journal

British journal of anaesthesia
ISSN: 1471-6771
Titre abrégé: Br J Anaesth
Pays: England
ID NLM: 0372541

Informations de publication

Date de publication:
09 2020
Historique:
received: 31 01 2020
revised: 07 04 2020
accepted: 03 05 2020
pubmed: 15 7 2020
medline: 17 9 2020
entrez: 15 7 2020
Statut: ppublish

Résumé

Recent studies point to a fundamental distinction between population-based and individual-based anaesthetic pharmacology. At the population level, anaesthetic potency is defined as the relationship between drug concentration and the likelihood of response to a stimulus. At the individual level, even when the anaesthetic concentration is held constant, fluctuations between the responsive and unresponsive states are observed. Notably, these spontaneous fluctuations exhibit resistance to state transitions R Adult (14-24 weeks old) C57BL/6J male mice (n=60) were subjected to repeated righting reflex (RR) assays at equipotent steady-state concentrations of isoflurane (0.6 vol%), sevoflurane (1.0 vol%), and halothane (0.4 vol%). Fluctuations in RR were observed for all tested anaesthetics. Analysis of these fluctuations revealed that R Whilst equipotent doses of distinct anaesthetics produce comparable population response probabilities, they engage dramatically different dynamics in each individual animal. This manifests as a differential aggregate propensity to exhibit state transitions. Thus, resistance to state transitions is a fundamentally distinct, novel measure of individualised anaesthetic pharmacology.

Sections du résumé

BACKGROUND
Recent studies point to a fundamental distinction between population-based and individual-based anaesthetic pharmacology. At the population level, anaesthetic potency is defined as the relationship between drug concentration and the likelihood of response to a stimulus. At the individual level, even when the anaesthetic concentration is held constant, fluctuations between the responsive and unresponsive states are observed. Notably, these spontaneous fluctuations exhibit resistance to state transitions R
METHODS
Adult (14-24 weeks old) C57BL/6J male mice (n=60) were subjected to repeated righting reflex (RR) assays at equipotent steady-state concentrations of isoflurane (0.6 vol%), sevoflurane (1.0 vol%), and halothane (0.4 vol%).
RESULTS
Fluctuations in RR were observed for all tested anaesthetics. Analysis of these fluctuations revealed that R
CONCLUSIONS
Whilst equipotent doses of distinct anaesthetics produce comparable population response probabilities, they engage dramatically different dynamics in each individual animal. This manifests as a differential aggregate propensity to exhibit state transitions. Thus, resistance to state transitions is a fundamentally distinct, novel measure of individualised anaesthetic pharmacology.

Identifiants

DOI: 10.1016/j.bja.2020.05.031 PMID: 32660718 PMC: PMC7497031
pubmed: 32660718
pii: S0007-0912(20)30413-X
doi: 10.1016/j.bja.2020.05.031
pmc: PMC7497031
pii:
doi:

Substances chimiques

Anesthetics, Inhalation 0
Sevoflurane 38LVP0K73A
Isoflurane CYS9AKD70P
Halothane UQT9G45D1P

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

308-320

Subventions

Organisme : NIGMS NIH HHS
ID : K08 GM123317
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124023
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM088156
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM107117
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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Auteurs

Andrzej Z Wasilczuk (AZ)

Department of Anaesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA, USA; Department of Bioengineering, School of Engineering and Applied Science, Philadelphia, PA, USA.

Benjamin A Harrison (BA)

Department of Anaesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA, USA.

Paula Kwasniewska (P)

Department of Anaesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA, USA.

Bo Ku (B)

Department of Anaesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA, USA.

Max B Kelz (MB)

Department of Anaesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA, USA; Department of Bioengineering, School of Engineering and Applied Science, Philadelphia, PA, USA; Chronobiology and Sleep Institute, University of Pennsylvania, Philadelphia, PA, USA.

Andrew R McKinstry-Wu (AR)

Department of Anaesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: andrew.mckinstry@pennmedicine.upenn.edu.

Alex Proekt (A)

Department of Anaesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA, USA; Chronobiology and Sleep Institute, University of Pennsylvania, Philadelphia, PA, USA.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Dépresseurs du système nerveux central › Anesthésiques › Anesthésiques généraux › Anesthésiques par inhalation › Resistance to state transitions in...
questionsmedicales.fr › Eucaryotes › Animaux › Resistance to state transitions in...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures halogénés › Halothane › Resistance to state transitions in...
questionsmedicales.fr › Composés chimiques organiques › Éthers › Éthers méthyliques › Isoflurane › Resistance to state transitions in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Resistance to state transitions in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Resistance to state transitions in...
questionsmedicales.fr › Techniques d'investigation › Modèles animaux › Resistance to state transitions in...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Réflexe › Réflexe de redressement › Resistance to state transitions in...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures halogénés › Hydrocarbures fluorés › Sévoflurane › Resistance to state transitions in...