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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
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