Anesthetic synergy between two n-alkanes - PubMed (original) (raw)

Anesthetic synergy between two n-alkanes

Robert J Brosnan et al. Vet Anaesth Analg. 2017 May.

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.

Keywords: N-methyl-d-aspartate receptor; inhaled anesthetics; isobologram; mechanism of action; minimum alveolar concentration; γ-aminobutyric acid type A receptor.

Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

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Figures

Figure 1

Figure 1

Sample electrophysiology tracings from two electrode voltage clamp studies of oocytes expressing (a) GABAA or (b) NMDA receptors before, during, and after exposure to solutions containing approximately 30% of an atmosphere n-butane.

Figure 2

Figure 2

Concentration-dependent effects of (a) butane or (b) pentane on potentiation of GABAA receptor currents measured using a two-electrode voltage clamp in oocytes.

Figure 3

Figure 3

Concentration-dependent effects of butane on inhibition of NMDA receptor currents measured using a two-electrode voltage clamp in oocytes. Pentane (not shown) did not modulate NMDA receptor currents even at saturated aqueous concentrations.

Figure 4

Figure 4

Isobologram (solid line) with two-tailed 95% confidence bounds (dotted lines) for butane and pentane concentrations at 1 × MAC in rats. Data markers represent the mean values for 8–10 rats each; error bars denote SEM. Combinations significantly outside of the lower isobologram 95% confidence bound are indicated by an asterisk (*) and _p_-value.

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