Tolerance to Isoflurane Does Not Occur in Developing Xenopus laevis Tadpoles

Milutinovic, Pavle S.; Zhao, Jing; Sonner, James M.

doi:10.1213/ane.0b013e31818ca33e

Cited by 4 publications

(3 citation statements)

References 22 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%

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%

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

The Journal of Pharmacology and Experimental Therapeutics

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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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“…Both methylmalonic acid and propionic acid had to be coadministered with isoflurane or the tadpoles would not recover over the concentration range that prevented movement. When coadministered with 0.3% isoflurane (a concentration equal to half isoflurane’s EC 50 (22)), 75.0 ± 9.1 mM propionic acid (Hill number n = 1.4 ± 0.4), or 149.6 ± 2.1 mM methylmalonic acid (Hill number n = 12.4 ± 2.0) had to be present in the bath to reversibly anesthetize the tadpoles. See Fig 2.…”

Section: Resultsmentioning

confidence: 99%

Isovaleric, Methylmalonic, and Propionic Acid Decrease Anesthetic EC50 in Tadpoles, Modulate Glycine Receptor Function, and Interact with the Lipid 1,2-Dipalmitoyl-Sn-Glycero-3-Phosphocholine

Weng¹,

Hsu²,

Zhao³

et al. 2009

Anesthesia &Amp; Analgesia

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Introduction Elevated concentrations of isovaleric, methylmalonic, and propionic acid are associated with impaired consciousness in genetic diseases (organic acidemias). We conjectured that part of the central nervous system depression observed in these disorders was due to anesthetic effects of these metabolites. We tested three hypotheses. First, that these metabolites would have anesthetic-sparing effects, possibly being anesthetics by themselves. Second, that these compounds would modulate glycine and GABAA receptor function, increasing chloride currents through these channels as potent clinical inhaled anesthetics do. Third, that these compounds would affect physical properties of lipids. Methods Anesthetic EC50’s were measured in Xenopus laevis tadpoles. Glycine and GABAA receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. Pressure-area isotherms of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were measured with and without added organic acids. Results Isovaleric acid was an anesthetic in tadpoles, while methylmalonic and propionic acid decreased isoflurane’s EC50 by half. All three organic acids concentration-dependently increased current through α1 glycine receptors. There were minimal effects on α1β2γ2s GABAA receptors. The organic acids increased total lateral pressure (surface pressure) of DPPC monolayers, including at mean molecular areas typical of bilayers. Conclusion Isovaleric, methylmalonic, and propionic acid have anesthetic affects in tadpoles, positively modulate glycine receptor fuction, and affect physical properties of DPPC monolayers.

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Tolerance to Isoflurane Does Not Occur in Developing Xenopus laevis Tadpoles

Cited by 4 publications

References 22 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?

Isovaleric, Methylmalonic, and Propionic Acid Decrease Anesthetic EC50 in Tadpoles, Modulate Glycine Receptor Function, and Interact with the Lipid 1,2-Dipalmitoyl-Sn-Glycero-3-Phosphocholine

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