Nellgård B, Mackensen G B, Massey G, Pearlstein R D, Warner D S
Neuroanesthesia Research Laboratory, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Anesth Analg. 2000 Jul;91(1):145-51. doi: 10.1097/00000539-200007000-00027.
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.
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.
与使用芬太尼+笑气麻醉相比，接受前脑缺血的大鼠在使用异氟烷麻醉时损伤减轻。异氟烷引起的保护作用可被三甲噻方逆转。我们推测这些麻醉药物对缺血结局的依赖性作用可能与缺血应激反应的改变有关。将大鼠随机分为四种处理组：异氟烷；芬太尼+笑气；异氟烷+三甲噻方；或异氟烷+甲吡酮。然后诱导严重前脑缺血10分钟。检测血浆和脑皮质酮、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6。异氟烷组和异氟烷+三甲噻方组的血浆皮质酮浓度相似，但高于芬太尼+笑气组和异氟烷+甲吡酮组。除异氟烷+甲吡酮组（其值明显降低）外，所有组的脑皮质酮相似。在异氟烷中加入甲吡酮也降低了血浆TNF-α；然而，其他组的值相似。各组之间脑TNF-α无差异。血浆IL-6浓度低于检测限。脑IL-6浓度因缺血而升高；然而，各组之间无差异。总之，异氟烷组和异氟烷+三甲噻方组在任何测量的应激标志物方面均无差异。此外，异氟烷组和芬太尼+笑气组之间除血浆皮质酮浓度外几乎没有差异。因此，异氟烷的神经保护作用及其被三甲噻方逆转似乎与本研究中测量的应激反应无关。
麻醉药物对缺血结局的不同影响与对缺血的肾上腺素能/去甲肾上腺素能反应无关。麻醉药物对皮质酮或细胞因子对缺血反应没有一致的差异作用，这进一步反驳了异氟烷神经保护作用可归因于减轻对缺血性损伤的不良应激反应这一假说。
