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LETTER TO THE EDITOR

Postischemic Nitrous Oxide Alone Versus Intraischemic Nitrous Oxide in the Presence of Isoflurane: What It May Change for Neuroprotection Against Cerebral Stroke in the Rat

Departments of Anesthesiology, Neurobiology, and Surgery; Duke University Medical Center; Durham, NC; warne002{at}mc.duke.edu

In Response:

We believe that the mechanism proposed by Abriani et al. is interesting. Indeed, evidence that nitrous oxide potentiates isoflurane neurotoxicity in the neonatal rat brain has been presented (1). It is reasonable to ask if such an interaction was also present in our study (2) that served to obscure an intra-ischemic protective effect of nitrous oxide. Specific investigation would be required to answer that question. However, we believe that such an explanation is unlikely. First, we will be convinced of any postischemic neuroprotective effect of nitrous oxide when evidence for this property is derived from a brain (or pericranial) temperature-controlled model (3) that provides prolonged outcome analysis (4). Second, if the purported site of action of nitrous oxide is the N-methyl-d-aspartate receptor, we should have observed the same interaction with the selective N-methyl-d-aspartate antagonist dizocilpine. To the contrary, dizocilpine given in the same context of isoflurane exposure provided a sustained and substantial neuroprotective effect. Finally, although there was some overlap in "co-presence" of isoflurane and nitrous oxide while the animal was awakening at onset of middle cerebral artery occlusion (i.e., during isoflurane elimination) and also when the animal was being reanesthetized with isoflurane to allow removal of the occlusive filament to terminate middle cerebral artery occlusion, these intervals were brief and thus constituted a small fraction of the 75-min middle cerebral artery occlusion interval. In contrast, evidence that nitrous oxide exacerbates perinatal rat brain injury induced by isoflurane was obtained from animals subjected to both drugs for 6 h (1).

References

1. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003;23:876–82.[Abstract/Free Full Text]
2. Yokoo N, Sheng H, Mixco J, et al. Intraischemic nitrous oxide alters neither neurologic nor histologic outcome: A comparison with dizocilpine. Anesth Analg 2004;99:896–903.[Abstract/Free Full Text]
3. Davies LM, MacLellan CL, Corbett DR, Colbourne F. Post-ischemic diazepam does not reduce hippocampal CA1 injury and does not improve hypothermic neuroprotection after forebrain ischemia in gerbils. Brain Res 2004;1013:223–9.[Web of Science][Medline]
4. Kawaguchi M, Kimbro JR, Drummond JC, et al. Isoflurane delays but does not prevent cerebral infarction in rats subjected to focal ischemia. Anesthesiology 2000;92:1335–42.[Web of Science][Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Warner, D. S. Articles by Yokoo, N. Search for Related Content PubMed Articles by Warner, D. S. Articles by Yokoo, N.