Anti-inflammatory effects of sevoflurane and mild hypothermia in endotoxemic rats

Anti-inflammatory effects of sevoflurane and mild hypothermia in endotoxemic rats
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DOI:
10.1111/j.1399-6576.2007.01353.x
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发表时间:
2007-08-01
影响因子:
2.1
通讯作者:
Zwissler, B.
Zwissler, B.
中科院分区:
医学4区
文献类型:
--
作者:
Hofstetter, C.;Boost, K. A.;Zwissler, B.

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背景:挥发性麻醉剂和低温可减弱炎症反应。目的:比较七氟醚和亚低温对实验性内毒素血症大鼠的抗炎作用。方法:麻醉通气型SD大鼠,每组6只,单纯给予脂多糖(LPS),静脉注射脂多糖(LPS5 mg/kg)。没有进一步的治疗。内毒素-亚低温组于注射内毒素(LPS5 mg/kg)后15min降温至33℃。内毒素-七氟醚组在诱导内毒素血症后15min开始吸入七氟醚(1MAC)。内毒素血症诱导后15min,内毒素-七氟醚-亚低温组给予七氟醚-亚低温联合降温。假手术组作为对照组,不给予内毒素血症或治疗。内毒素血症4h后,检测血浆肿瘤坏死因子-α(TNF-α)、白介素1-β(IL-1β)和IL-10水平。结果:吸入七氟醚后,肺泡巨噬细胞(AM)中的肿瘤坏死因子-α(-60%,P<0.05)和IL-1β(-68%,P<0.05)水平明显低于单纯内毒素组。低温及其与七氟醚联合应用显著降低了肿瘤坏死因子-α水平(分别为-46%和-58%,P均<0.05),但不降低IL-1β水平。与内毒素血症对照组相比,应用亚低温及其与七氟醚联合应用可使血浆IL-10显著升高。七氟醚(-83%)、低温(-73%)及两者合用均能显著抑制AM亚硝酸盐的释放(P&lt;0.05)。结论:七氟醚和亚低温可减轻体内内毒素血症时的炎症反应,有助于临床器官保护。
Background: Volatile anesthetics and hypothermia attenuate the inflammatory response. We aimed to compare the anti-inflammatory effects of sevoflurane and mild hypothermia during experimental endotoxemia in the rat.Methods: Anesthetized, ventilated Sprague-Dawley (SD) rats were randomly treated as follows (n = 6 per group): lipopolysaccharide (LPS) only, animals received LPS [LPS 5 mg/kg, intravenously (i.v.)] with no further treatment. In the LPS-hypothermia group, rats were cooled down to a temperature of 33 degrees C 15 min after LPS-injection (LPS 5 mg/kg i.v.). In animals of the LPS-sevoflurane group, sevoflurane inhalation (1 MAC) was initiated 15 min after induction of endotoxemia. The LPS-sevoflurane-hypothermia group received combined sevoflurane and hypothermia 15 min after induction of endotoxemia. A Sham group served as control without endotoxemia or treatment. After 4 h of endotoxemia, plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-10 were measured. Alveolar macrophages (AM) were ex vivo cultured for nitrite assay.Results: Inhalation of sevoflurane significantly attenuated plasma levels of TNF-alpha (-60%, P < 0.05) and IL-1 beta (-68%, P < 0.05) as compared with the LPS-only group. Hypothermia and its combination with sevoflurane significantly reduced TNF-alpha levels (-46% and -58%, each P < 0.05), but not IL-1 beta. Application of mild hypothermia and also its combination with sevoflurane resulted in a significant increase in plasma IL-10 as compared with endotoxemic controls. Nitrite release from AM was found to be significantly suppressed by sevoflurane (-83%), hypothermia (-73%) and by the combination of both (-67%) (P < 0.05, each).Conclusion: Our data suggest that sevoflurane and mild hypothermia attenuate the inflammatory response during endotoxemia in vivo thus contributing to their beneficial role in clinical organ protection.