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Correspondence  |   July 2004
Neuroprotection by Nitrous Oxide and Xenon and Its Relation to Minimum Alveolar Concentration
Author Affiliations & Notes
  • Jacques H. Abraini, Ph.D., D.Sc.
    *
  • * Université de Caen Basse Normandie and Air Liquide Santé International, Paris, France.
Article Information
Correspondence
Correspondence   |   July 2004
Neuroprotection by Nitrous Oxide and Xenon and Its Relation to Minimum Alveolar Concentration
Anesthesiology 7 2004, Vol.101, 260-261. doi:
Anesthesiology 7 2004, Vol.101, 260-261. doi:
To the Editor:—
We read with a real interest the recent article by Homi et al.  ,1 published in the October 2003 issue of Anesthesiology, on the neuroprotective effect of xenon administration during transient middle cerebral artery occlusion in mice. Briefly, the authors showed that 70 vol% xenon decreased cerebral infarct volume and improved neurologic outcome when compared with 70 vol% nitrous oxide, whereas a mixture of 35 vol% xenon plus 35 vol% nitrous oxide had an intermediate neuroprotective action. Based on the assumption taken from previous data2,3 that xenon and nitrous oxide, which both provide N  -methyl-d-aspartate (NMDA) receptor antagonism,4,5 would have a similar minimum alveolar anesthetic concentration (MAC), Dr. Homi et al.  proposed that differences in cerebral infarct volume and neurologic outcome after treatment with xenon, nitrous oxide, or both would not result from variations in MAC between groups but rather from the fact that xenon may be a more potent NMDA receptor antagonist than nitrous oxide.
This work, together with our concomitant article6 published in the October 2003 issue of the Journal of Cerebral Blood Flow and Metabolism  , provides evidence that xenon may have a clinical potential as a neuroprotective agent for stroke treatment. However, it seems to us that some of the possible mechanisms that may explain the more potent neuroprotective action of xenon compared with nitrous oxide might have been overlooked.
To compare gases with “anesthetic” action, it might be important to distinguish between analgesic potency, as measured by the absence of response to a noxious stimulus, and narcotic (hypnotic) potency, as measured by loss of the righting reflex. Using loss of the righting reflex as a measure of narcotic potency and slow compression rates to avoid compression-rate–dependent distortion of narcotic potency in rats, we found MAC values for krypton (unpublished data), nitrogen, argon, nitrous oxide, and xenon6,7 that are similar to the experimental MAC values found in mice for these gases,3,8,9 as well as to those predicted for rats.3 So far as nitrous oxide and xenon are concerned, we found that these gases were effective at producing loss of the righting reflex at 128 ± 2.9 and 86 ± 2.3 vol%, respectively.6 This indicated that the narcotic potency of xenon is 1.48-fold higher than that of nitrous oxide, a value similar to the MAC ratio of nitrous oxide and xenon in humans.10,11 Accordingly, we showed that 50 vol% xenon and 75 vol% nitrous oxide have a similar effect at reducing NMDA-induced increase in Ca2+influx in mice cortical cultured neurons as well as cortical infarct volume in rats compared with controls animals treated with air when given after transient middle cerebral artery occlusion (i.e.  , after restoration of cerebral blood flow, a condition needed to make these agents therapeutically valuable).6 In addition, in agreement with data that suggested that xenon at concentrations higher than 70 vol% may produce adverse effects,12,13 we found that 75 vol% xenon shows potentially neurotoxic effects when given after transient middle cerebral artery occlusion6; interestingly, according to the MAC ratio of nitrous oxide and xenon, xenon at 75 vol% can be considered equipotent to 111 vol% nitrous oxide, a concentration that is not far from that of 117 vol%, at which nitrous oxide exhibits neurotoxic properties related to its NMDA receptor antagonistic action.5 Together, these data provide evidence that the neuroprotective action and NMDA antagonistic properties of nitrous oxide and xenon depend on their MAC ratio. Therefore, the interesting data reported by Dr. Homi et al.  on the intermediate neuroprotective effect of 35 vol% xenon plus 35 vol% nitrous oxide, compared to 70 vol% xenon and 70 vol% nitrous oxide, can be easily interpreted on the basis of the MAC ratio of nitrous oxide and xenon, because 35 vol% xenon plus 35 vol% nitrous oxide can be considered equivalent to 87 vol% nitrous oxide, whereas xenon at 70 vol% can be considered equivalent to 104 vol% nitrous oxide.
* Université de Caen Basse Normandie and Air Liquide Santé International, Paris, France.
References
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