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BMC Anesthesiology
Published in: BMC Anesthesiology 1/2012

Open Access 01-12-2012 | Research article

Increased NMDA receptor inhibition at an increased Sevoflurane MAC

Authors: Robert J Brosnan, Roberto Thiesen

Published in: BMC Anesthesiology | Issue 1/2012

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Abstract

Background

Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC) could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC.

Methods

Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF) containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL) plus 0.4 mg/mL dizocilpine (MK-801) was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured.

Results

Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P < 0.005) difference that is consistent with increased NMDA receptor antagonism by sevoflurane in rats receiving strychnine.

Conclusions

Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.
Appendix
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Metadata
Title
Increased NMDA receptor inhibition at an increased Sevoflurane MAC
Authors
Robert J Brosnan
Roberto Thiesen
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2012
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/1471-2253-12-9

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