Anesthetic synergy between two n-alkanes

Robert J Brosnan, Fabíola B. Fukushima, Trung L. Pham

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective N-butane and n-pentane can both produce general anesthesia. Both compounds potentiate γ-aminobutyric acid type A (GABAA) receptor function, but only butane inhibits N-methyl-D-aspartate (NMDA) receptors. It was hypothesized that butane and pentane would exhibit anesthetic synergy due to their different actions on ligand-gated ion channels. Study design Prospective experimental study. Animals A total of four Xenopus laevis frogs and 43 Sprague–Dawley rats. Methods Alkane concentrations for all studies were determined via gas chromatography. Using a Xenopus oocyte expression model, standard two-electrode voltage clamp techniques were used to measure NMDA and GABAA receptor responses in vitro as a function of butane and pentane concentrations relevant to anesthesia. The minimum alveolar concentrations (MAC) of butane and pentane were measured separately in rats, and then pentane MAC was measured during coadministration of 0.25, 0.50 or 0.75 times MAC of butane. An isobole with 95% confidence intervals was constructed using regression analysis. A sum of butane and pentane that was statistically less than the lower-end confidence bound isobole indicated a synergistic interaction. Results Both butane and pentane dose-dependently potentiated GABAA receptor currents over the study concentration range. Butane dose-dependently inhibited NMDA receptor currents, but pentane did not modulate NMDA receptors. Butane and pentane MAC in rats was 39.4 ± 0.7 and 13.7 ± 0.4 %, respectively. A small but significant (p < 0.03) synergistic anesthetic effect with pentane was observed during administration of either 0.50 or 0.75 × MAC butane. Conclusions Butane and pentane show synergistic anesthetic effects in vivo consistent with their different in vitro receptor effects. Clinical relevance Findings support the relevance of NMDA receptors in mediating anesthetic actions for some, but not all, inhaled agents.

Original languageEnglish (US)
Pages (from-to)577-588
Number of pages12
JournalVeterinary Anaesthesia and Analgesia
Volume44
Issue number3
DOIs
StatePublished - May 1 2017

Fingerprint

Alkanes
pentane
anesthetics
alkanes
Anesthetics
aspartic acid
N-Methyl-D-Aspartate Receptors
receptors
GABA-A Receptors
butanes
butane
rats
anesthesia
Ligand-Gated Ion Channels
Aminobutyrates
patch-clamp technique
Xenopus laevis
ion channels
Xenopus
Patch-Clamp Techniques

Keywords

  • inhaled anesthetics
  • isobologram
  • mechanism of action
  • minimum alveolar concentration
  • N-methyl-D-aspartate receptor
  • γ-aminobutyric acid type A receptor

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Anesthetic synergy between two n-alkanes. / Brosnan, Robert J; Fukushima, Fabíola B.; Pham, Trung L.

In: Veterinary Anaesthesia and Analgesia, Vol. 44, No. 3, 01.05.2017, p. 577-588.

Research output: Contribution to journalArticle

Brosnan, Robert J ; Fukushima, Fabíola B. ; Pham, Trung L. / Anesthetic synergy between two n-alkanes. In: Veterinary Anaesthesia and Analgesia. 2017 ; Vol. 44, No. 3. pp. 577-588.
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abstract = "Objective N-butane and n-pentane can both produce general anesthesia. Both compounds potentiate γ-aminobutyric acid type A (GABAA) receptor function, but only butane inhibits N-methyl-D-aspartate (NMDA) receptors. It was hypothesized that butane and pentane would exhibit anesthetic synergy due to their different actions on ligand-gated ion channels. Study design Prospective experimental study. Animals A total of four Xenopus laevis frogs and 43 Sprague–Dawley rats. Methods Alkane concentrations for all studies were determined via gas chromatography. Using a Xenopus oocyte expression model, standard two-electrode voltage clamp techniques were used to measure NMDA and GABAA receptor responses in vitro as a function of butane and pentane concentrations relevant to anesthesia. The minimum alveolar concentrations (MAC) of butane and pentane were measured separately in rats, and then pentane MAC was measured during coadministration of 0.25, 0.50 or 0.75 times MAC of butane. An isobole with 95{\%} confidence intervals was constructed using regression analysis. A sum of butane and pentane that was statistically less than the lower-end confidence bound isobole indicated a synergistic interaction. Results Both butane and pentane dose-dependently potentiated GABAA receptor currents over the study concentration range. Butane dose-dependently inhibited NMDA receptor currents, but pentane did not modulate NMDA receptors. Butane and pentane MAC in rats was 39.4 ± 0.7 and 13.7 ± 0.4 {\%}, respectively. A small but significant (p < 0.03) synergistic anesthetic effect with pentane was observed during administration of either 0.50 or 0.75 × MAC butane. Conclusions Butane and pentane show synergistic anesthetic effects in vivo consistent with their different in vitro receptor effects. Clinical relevance Findings support the relevance of NMDA receptors in mediating anesthetic actions for some, but not all, inhaled agents.",
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N2 - Objective N-butane and n-pentane can both produce general anesthesia. Both compounds potentiate γ-aminobutyric acid type A (GABAA) receptor function, but only butane inhibits N-methyl-D-aspartate (NMDA) receptors. It was hypothesized that butane and pentane would exhibit anesthetic synergy due to their different actions on ligand-gated ion channels. Study design Prospective experimental study. Animals A total of four Xenopus laevis frogs and 43 Sprague–Dawley rats. Methods Alkane concentrations for all studies were determined via gas chromatography. Using a Xenopus oocyte expression model, standard two-electrode voltage clamp techniques were used to measure NMDA and GABAA receptor responses in vitro as a function of butane and pentane concentrations relevant to anesthesia. The minimum alveolar concentrations (MAC) of butane and pentane were measured separately in rats, and then pentane MAC was measured during coadministration of 0.25, 0.50 or 0.75 times MAC of butane. An isobole with 95% confidence intervals was constructed using regression analysis. A sum of butane and pentane that was statistically less than the lower-end confidence bound isobole indicated a synergistic interaction. Results Both butane and pentane dose-dependently potentiated GABAA receptor currents over the study concentration range. Butane dose-dependently inhibited NMDA receptor currents, but pentane did not modulate NMDA receptors. Butane and pentane MAC in rats was 39.4 ± 0.7 and 13.7 ± 0.4 %, respectively. A small but significant (p < 0.03) synergistic anesthetic effect with pentane was observed during administration of either 0.50 or 0.75 × MAC butane. Conclusions Butane and pentane show synergistic anesthetic effects in vivo consistent with their different in vitro receptor effects. Clinical relevance Findings support the relevance of NMDA receptors in mediating anesthetic actions for some, but not all, inhaled agents.

AB - Objective N-butane and n-pentane can both produce general anesthesia. Both compounds potentiate γ-aminobutyric acid type A (GABAA) receptor function, but only butane inhibits N-methyl-D-aspartate (NMDA) receptors. It was hypothesized that butane and pentane would exhibit anesthetic synergy due to their different actions on ligand-gated ion channels. Study design Prospective experimental study. Animals A total of four Xenopus laevis frogs and 43 Sprague–Dawley rats. Methods Alkane concentrations for all studies were determined via gas chromatography. Using a Xenopus oocyte expression model, standard two-electrode voltage clamp techniques were used to measure NMDA and GABAA receptor responses in vitro as a function of butane and pentane concentrations relevant to anesthesia. The minimum alveolar concentrations (MAC) of butane and pentane were measured separately in rats, and then pentane MAC was measured during coadministration of 0.25, 0.50 or 0.75 times MAC of butane. An isobole with 95% confidence intervals was constructed using regression analysis. A sum of butane and pentane that was statistically less than the lower-end confidence bound isobole indicated a synergistic interaction. Results Both butane and pentane dose-dependently potentiated GABAA receptor currents over the study concentration range. Butane dose-dependently inhibited NMDA receptor currents, but pentane did not modulate NMDA receptors. Butane and pentane MAC in rats was 39.4 ± 0.7 and 13.7 ± 0.4 %, respectively. A small but significant (p < 0.03) synergistic anesthetic effect with pentane was observed during administration of either 0.50 or 0.75 × MAC butane. Conclusions Butane and pentane show synergistic anesthetic effects in vivo consistent with their different in vitro receptor effects. Clinical relevance Findings support the relevance of NMDA receptors in mediating anesthetic actions for some, but not all, inhaled agents.

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