We are most appreciative of the interest of Dr. Abraini et al. in our recent work examining the neuroprotective effect of xenon administration during transient middle cerebral artery occlusion in mice. Although they are in agreement with our interpretation that xenon possesses significant neuroprotective properties, their explanation for the apparent concentration response that we demonstrated (i.e. , 35% Xe in combination with 35% N2O having less neuroprotection than 70% Xe alone) differs from our own.
The disagreement centers on the definition of anesthetic equivalence between nitrous oxide and xenon. Whereas we believe that the animals received equivalent levels of anesthesia based on the common definition of minimum alveolar concentration (MAC; response to a noxious stimuli; MAC Xe, 160%,1MAC N2O, 150%2), thus making it unlikely that differences in anesthetic depth influenced our results, Abraini et al. believe that loss of the righting reflex is a more relevant marker of equivalence, thus questioning our assumption that the anesthetic depth was similar. Undoubtedly, the issue of equivalence is clouded by the surprisingly wide ranges for published anesthetic potency measures such as MAC (determined with tail clamping), loss of righting reflex, and responses to either tail flick or electrical stimulation.3–6If one adds to this the unresolved issues related to unexplained interspecies differences, one can simply conclude that the determination of anesthetic equivalence is anything but exact.
However, arguably more relevant than anesthetic equivalence is the issue of N -methyl-d-aspartate receptor potency, for which there is little data available for determining whether the concentrations of xenon and nitrous oxide that we used have similar ability to antagonize N -methyl-d-aspartate receptors and thus produce a neuroprotective effect. We assume that if we administered the gases at the same concentration (and thus with anesthetic equivalence),1,2because xenon was found to be neuroprotective, either there are differences in the ability of these gases to antagonize N -methyl-d-aspartate receptors or xenon possesses neuroprotective properties by acting at other targets, or both.7
* Duke University Medical Center, Durham, North Carolina. firstname.lastname@example.org