Naturally Occurring Variability in Anesthetic Potency Among Inbred Mouse Strains

Sonner, James M.; Gong, Diane; Eger, Edmond I.

doi:10.1097/00000539-200009000-00042

Cited by 62 publications

(45 citation statements)

References 18 publications

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“…The small difference in MAC LORR for halothane (our determination is 13% greater than theirs) is easily accounted by the different genetic background of their mice which could influence anesthetic sensitivity by as much as 40% [32]. Our best fit values for Hill coefficients are within the expected range for volatile anesthetics of 20–30 [33].…”

Section: Discussionmentioning

confidence: 75%

High throughput modular chambers for rapid evaluation of anesthetic sensitivity

et al. 2006

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BackgroundAnesthetic sensitivity is determined by the interaction of multiple genes. Hence, a dissection of genetic contributors would be aided by precise and high throughput behavioral screens. Traditionally, anesthetic phenotyping has addressed only induction of anesthesia, evaluated with dose-response curves, while ignoring potentially important data on emergence from anesthesia.MethodsWe designed and built a controlled environment apparatus to permit rapid phenotyping of twenty-four mice simultaneously. We used the loss of righting reflex to indicate anesthetic-induced unconsciousness. After fitting the data to a sigmoidal dose-response curve with variable slope, we calculated the MACLORR (EC50), the Hill coefficient, and the 95% confidence intervals bracketing these values. Upon termination of the anesthetic, Emergence timeRR was determined and expressed as the mean ± standard error for each inhaled anesthetic.ResultsIn agreement with several previously published reports we find that the MACLORR of halothane, isoflurane, and sevoflurane in 8–12 week old C57BL/6J mice is 0.79% (95% confidence interval = 0.78 – 0.79%), 0.91% (95% confidence interval = 0.90 – 0.93%), and 1.96% (95% confidence interval = 1.94 – 1.97%), respectively. Hill coefficients for halothane, isoflurane, and sevoflurane are 24.7 (95% confidence interval = 19.8 – 29.7%), 19.2 (95% confidence interval = 14.0 – 24.3%), and 33.1 (95% confidence interval = 27.3 – 38.8%), respectively. After roughly 2.5 MACLORR • hr exposures, mice take 16.00 ± 1.07, 6.19 ± 0.32, and 2.15 ± 0.12 minutes to emerge from halothane, isoflurane, and sevoflurane, respectively.ConclusionThis system enabled assessment of inhaled anesthetic responsiveness with a higher precision than that previously reported. It is broadly adaptable for delivering an inhaled therapeutic (or toxin) to a population while monitoring its vital signs, motor reflexes, and providing precise control over environmental conditions. This system is also amenable to full automation. Data presented in this manuscript prove the utility of the controlled environment chambers and should allow for subsequent phenotyping of mice with targeted mutations that are expected to alter sensitivity to induction or emergence from anesthesia.

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Section: Discussionmentioning

confidence: 75%

High throughput modular chambers for rapid evaluation of anesthetic sensitivity

et al. 2006

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“…8 Genetic differences between mouse strains may alter sensitivity to anesthetics. 14,15 We did, however, match the strains as closely as possible. The reported difference in anesthetic sensitivity between the 129 and C57BL/6J strains is small for most drugs and is statistically indistinguishable for the anesthetics used in this study.…”

Section: Discussionmentioning

confidence: 99%

“…The reported difference in anesthetic sensitivity between the 129 and C57BL/6J strains is small for most drugs and is statistically indistinguishable for the anesthetics used in this study. 15 Although it is recognized that the hybrid could have different sensitivity than either pure strain, this behavior has not been reported for anesthetics.…”

Section: Discussionmentioning

confidence: 99%

Inhaled Anesthetic Potency in Aged Alzheimer Mice

Bianchi¹,

Caltagarone²,

LaFerla³

et al. 2010

Anesthesia &Amp; Analgesia

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BACKGROUND The number of elderly patients with frank or incipient Alzheimer’s disease (AD) requiring surgery is growing as the population ages. General anesthesia may exacerbate symptoms of and the pathology underlying AD, so minimizing anesthetic exposure may be important. This requires knowledge of whether the continuing AD pathogenesis alters anesthetic potency. METHODS We determined the induction potency and emergence time for isoflurane, halothane, and sevoflurane using the minimum alveolar anesthetic concentration for loss of righting reflex as an end point in 12- to 14-mo-old triple transgenic Alzheimer (3xTgAD) mice and wild type C57BL6 controls. 3xTgAD mice model AD by harboring three distinct mutations: the APPSwe, Tau, and PS1 human transgenes, each of which has been associated with familial forms of human AD. RESULTS The 3xTgAD mice exhibited mild resistance (from 8% to 30%) to volatile anesthetics but displayed indistinguishable emergence patterns from all three inhaled anesthetics. CONCLUSIONS These results show that the genetic vulnerabilities and neuropathology associated with AD produce a small but significant decrease in sensitivity to the hypnotic actions of three inhaled anesthetics. Emergence times were not altered.

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“…This stimulus is a tail-clamp; forceps are applied to the base of the tail for 1 min. Using this stimulus, only modest differences in MAC have been found across various in-bred mouse strains (Sonner, Gong, & Eger, 2000;Sonner et al, 1999). For example, the MAC for the C57BL/6J strain is 1.30 vol% isoflurane or 1.28 vol% halothane, and is 1.40 vol% isoflurane or 1.30 vol% halothane for the 129/SvJ strain.…”

Section: Mouse General Anesthesia Endpoints Follow a Similar Trend Tomentioning

confidence: 99%

What is unconsciousness in a fly or a worm? A review of general anesthesia in different animal models

Zalucki

Swinderen

2016

Consciousness and Cognition

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Naturally Occurring Variability in Anesthetic Potency Among Inbred Mouse Strains

Abstract: Laboratory mouse strains differ significantly in susceptibility to anesthetics. These phenotypic differences may be exploited to help determine the genetic basis of anesthetic-induced immobility.

Cited by 62 publications

References 18 publications

High throughput modular chambers for rapid evaluation of anesthetic sensitivity

High throughput modular chambers for rapid evaluation of anesthetic sensitivity

Inhaled Anesthetic Potency in Aged Alzheimer Mice

What is unconsciousness in a fly or a worm? A review of general anesthesia in different animal models

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