The effects of anesthetics on stress responses to forebrain ischemia and reperfusion in the rat.
UNLABELLED: Rats exposed to forebrain ischemia have reduced injury when anesthetized with isoflurane versus fentanyl + N(2)O. The protection caused by isoflurane is reversed by trimethaphan. We hypothesized that these anesthetic-dependent effects on ischemic outcome can be associated with altered stress responses to ischemia. Rats were randomized to four treatments: isoflurane; fentanyl + N(2)O; isoflurane + trimethaphan; or isoflurane + metyrapone. Severe forebrain ischemia was then induced for 10 min. Plasma and brain corticosterone, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were assayed. Plasma corticosterone concentrations were similar in the isoflurane and isoflurane + trimethaphan groups, but greater than in the fentanyl + N(2)O and isoflurane + metyrapone groups. Brain corticosterone was similar among all groups except isoflurane + metyrapone, in which values were markedly reduced. The addition of metyrapone to isoflurane also reduced plasma TNF-alpha; however, values among other groups were similar. There were no differences among groups for brain TNF-alpha. Plasma IL-6 concentrations were below the limit of detection. Brain IL-6 concentrations were increased by ischemia; however, there was no difference among groups. In conclusion, there were no differences between the isoflurane and isoflurane + trimethaphan groups for any of the measured stress markers. Further, there was little difference between the isoflurane and fentanyl + N(2)O groups, except for plasma corticosterone concentration. Accordingly, isoflurane neuroprotection and its reversal by trimethaphan appear to be independent of effects on the stress responses measured in this study. IMPLICATIONS: Differential anesthetic effects on ischemic outcome are independent of effects on adrenergic/noradrenergic responses to ischemia. The absence of a consistent differential effect of anesthetics on either corticosterone or cytokine responses to ischemia serves to further refute the hypothesis that isoflurane neuroprotection can be attributed to dampening of adverse stress responses to ischemic insults.
Nellgård, B; Mackensen, GB; Massey, G; Pearlstein, RD; Warner, DS
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