The effects of anesthetics on stress responses to forebrain ischemia and reperfusion in the rat

Rats exposed to forebrain ischemia have reduced injury when anesthetized wi th isoflurane versus fentanyl + N2O. 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 + N2O; isoflurane + trimethaphan; or isoflurane + metyrapone. Severe foreb rain ischemia was then induced for 10 min. Plasma and brain corticosterone, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were assayed. Pl asma corticosterone concentrations were similar in the isoflurane and isofl urane + trimethaphan groups, but greater than in the fentanyl + N2O and iso flurane + metyrapone groups. Brain corticosterone was similar among all gro ups except isoflurane + metyrapone, in which values were markedly reduced. The addition of metyrapone to isoflurane also reduced plasma TNF-alpha; how ever, values among other groups were similar. There were no differences amo ng groups for brain TNF-alpha. Plasma IL-6 concentrations were below the li mit of detection. Brain IL-6 concentrations were increased by ischemia; how ever, there was no difference among groups. In conclusion, there were no di fferences between the isoflurane and isoflurane + trimethaphan groups for a ny of the measured stress markers. Further, there was Little difference bet ween the isoflurane and fentanyl + N2O groups, except for plasma corticoste rone concentration. Accordingly, isoflurane neuroprotection and its reversa l by trimethaphan appear to be independent of effects on the stress respons es measured in this study.