Murine auto- and cross-tolerance to volatile anaesthetics

Chalon, Jack; Tang, Chau-Kvei; Roberts, Craig S.; Walpert, Laura; Hoffman, Cheryl; Ramanathan, Sivam; Turndorf, Herman

doi:10.1007/bf03013800

Cited by 9 publications

(4 citation statements)

References 4 publications

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“…This flaw may be mitigated as short-term tolerance to volatile anesthetics does not occur, which makes cross-tolerance also doubtful. 47,61 We did not acquire respiratory data and cannot formally exclude intermittent hypoxia or hypoventilation during anesthetic exposures. We attempted to normalize exposures using equipotent anesthetic concentrations that were 1.2–1.3 times the ED 50 for loss of righting in mice.…”

Section: Discussionmentioning

confidence: 99%

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Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

et al. 2011

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Background General anesthesia has been likened to a state in which anesthetized subjects are locked out of access to both rapid eye movement (REM) sleep and wakefulness. Were this true for all anesthetics, one might expect a significant REM rebound following anesthetic exposure. However, for the intravenous anesthetic propofol, studies demonstrate that no sleep debt accrues. Moreover, pre-existing sleep debts dissipate during propofol anesthesia. To determine whether these effects are specific to propofol or are typical of volatile anesthetics we tested the hypothesis that REM sleep debt would accrue in rodents anesthetized with volatile anesthetics. Methods Electroencephalographic and electromyographic electrodes were implanted in 10 mice. After 9–11 days of recovery and habituation to a 12h:12h light:dark cycle, baseline states of wakefulness, non-rapid eye movement sleep, and REM sleep were recorded in mice exposed to 6 hours of an oxygen control and on separate days to 6 hours of isoflurane, sevoflurane, or halothane in oxygen. All exposures were conducted at the onset of light. Results Mice in all three anesthetized groups exhibited a significant doubling of REM sleep during the first six-hours of the dark phase of the circadian schedule while only mice exposed to halothane displayed a significant increase in non-rapid eye movement sleep that peaked at 152% of baseline. Conclusion REM sleep rebound following exposure to volatile anesthetics suggests that these volatile anesthetics do not fully substitute for natural sleep. This result contrasts with the published actions of propofol for which no REM sleep rebound occurred.

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Section: Discussionmentioning

confidence: 99%

“…Halothane was deliberately chosen to be last anesthetic based upon a published report of cross-tolerance. 47 …”

Section: Methodsmentioning

confidence: 99%

Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

et al. 2011

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“…H 2 S was always given as the final exposure. Prior work has established the lack of acute adaptation or tachyphylaxis to repeated anesthetic exposure (Chalon et al, 1983;Milutinovic et al, 2009).…”

Section: Raw and Processed Eeg And Emg Analysismentioning

confidence: 99%

Is Hydrogen Sulfide-Induced Suspended Animation General Anesthesia?

McKinstry²,

Moore³

et al. 2012

J Pharmacol Exp Ther

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Hydrogen sulfide (H 2 S) depresses mitochondrial function and thereby metabolic rates in mice, purportedly resulting in a state of "suspended animation." Volatile anesthetics also depress mitochondrial function, an effect that may contribute to their anesthetic properties. In this study, we ask whether H 2 S has general anesthetic properties, and by extension, whether mitochondrial effects underlie the state of anesthesia. We compared loss of righting reflex, electroencephalography, and electromyography in mice exposed to metabolically equipotent concentrations of halothane, isoflurane, sevoflurane, and H 2 S. We also studied combinations of H 2 S and anesthetics to assess additivity. Finally, the long-term effects of H 2 S were assessed by using the Morris water maze behavioral testing 2 to 3 weeks after exposures. Exposure to H 2 S decreases O 2 consumption, CO 2 production, and body temperature similarly to that of the general anesthetics, but fails to produce a loss of righting reflex or muscle atonia at metabolically equivalent concentrations. When combined, H 2 S antagonizes the metabolic effects of isoflurane, but potentiates the isoflurane-induced loss of righting reflex. We found no effect of prior H 2 S exposure on memory or learning. H 2 S (250 ppm), not itself lethal, produced delayed lethality when combined with subanesthetic concentrations of isoflurane. H 2 S cannot be considered a general anesthetic, despite similar metabolic suppression. Metabolic suppression, presumably via mitochondrial actions, is not sufficient to account for the hypnotic or immobilizing components of the anesthetic state. Combinations of H 2 S and isoflurane can be lethal, suggesting extreme care in the combination of these gases in clinical situations.

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“…Although the relative contributions of these targets toward anesthesia and sedation are not completely understood, it is clear that anesthetics act by reducing excitatory synaptic transmission and enhancing inhibitory synaptic transmission, which leads to a net reduction in neuronal activity (Hemmings 2009; Staiman and Seeman 1977). Tolerance can arise in response to a wide variety of sedating and abused substances, which can include—depending on the behavior measured—inhaled anesthetics (Chalon et al 1983; Smith et al 1979). Functional tolerance appears to be a homeostatic response to a reduction in neuronal activity, opposing the sedative effects of the drug by increasing neuronal excitability.…”

Section: Introductionmentioning

confidence: 99%

Tolerance to Anesthesia Depends on Synaptic Proteins

et al. 2011

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The hypnotic effects of anesthetics are caused by their interactions with neuronal components vital for proper signaling. An understanding of the adaptive mechanisms that lead to the development of anesthetic tolerance can offer insight into the regulation of neuroexcitability and plasticity that alter behavioral output. Here we use genetic and pharmacological manipulation of Drosophila to investigate the mechanisms of tolerance to benzyl alcohol. The mutants tested were temperature-sensitive paralytics that interfere with neuronal signaling: two mutations in dynamin that affect vesicle recycling, shits1 and shits2, and one that affects the voltage-activated Na+ channel, parats1. We also used N-ethylmaleimide (NEM) to pharmacologically interfere with synaptic function. We found that blocking the generation of action potentials using a temperature-sensitive paralytic mutation does not induce nor prevent the development of functional tolerance to benzyl alcohol, but that disruption of synaptic signaling using mutations in the dynamin gene or by NEM treatment inhibits the induction of tolerance.

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Murine auto- and cross-tolerance to volatile anaesthetics

Cited by 9 publications

References 4 publications

Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

Is Hydrogen Sulfide-Induced Suspended Animation General Anesthesia?

Tolerance to Anesthesia Depends on Synaptic Proteins

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