Abstract
Hydrogen sulfide (H2S) 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 H2S 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 H2S. We also studied combinations of H2S and anesthetics to assess additivity. Finally, the long-term effects of H2S were assessed by using the Morris water maze behavioral testing 2 to 3 weeks after exposures. Exposure to H2S decreases O2 consumption, CO2 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, H2S antagonizes the metabolic effects of isoflurane, but potentiates the isoflurane-induced loss of righting reflex. We found no effect of prior H2S exposure on memory or learning. H2S (250 ppm), not itself lethal, produced delayed lethality when combined with subanesthetic concentrations of isoflurane. H2S 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 H2S and isoflurane can be lethal, suggesting extreme care in the combination of these gases in clinical situations.
Footnotes
This research was supported by the National Institutes of Health National Institute of General Medical Sciences [Grants GM077357, GM088156] (to M.B.K.); the Mary Elizabeth Groff Foundation (M.B.K.); and the Austin Lamont Endowment (R.G.E.).
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
↵ The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.
ABBREVIATIONS:
- H2S
- hydrogen sulfide
- EEG
- electroencephalography
- EMG
- electromyography
- LORR
- loss of righting reflex
- ANOVA
- analysis of variance.
- Received August 24, 2011.
- Accepted March 12, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|