Sevoflurane Exposure Prevents Diaphragmatic Oxidative Stress During Mechanical Ventilation but Reduces Force and Affects Protein Metabolism Even During Spontaneous Breathing in a Rat Model
Sevoflurane Exposure Prevents Diaphragmatic Oxidative Stress During Mechanical Ventilation but Reduces Force and Affects Protein Metabolism Even During Spontaneous Breathing in a Rat Model
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DOI：
10.1213/ane.0000000000000736
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发表时间：
2015-07-01
影响因子：
5.7
通讯作者：
Bruells, Christian S.
中科院分区：
文献类型：
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作者：
Breuer, Thomas;Maes, Karen;Bruells, Christian S.
背景：呼吸机诱导的横隔膜功能障碍与氧化应激、蛋白降解增强、自噬和横隔膜蛋白质合成减少有关。七氟醚是一种常见的手术室麻醉剂，也可用于重症监护医学。除了它的麻醉特性外，如果在心脏手术开始时使用它，它在心脏缺血再灌注模型中的应用可以维持蛋白质的合成和抑制活性氧的产生。本研究假设七氟醚可能通过阻止氧化应激的产生来预防呼吸机诱导的横隔膜功能障碍。方法：4个月龄雄性SD大鼠给予七氟醚镇静(最低肺泡浓度=1)，机械通气(MV)12小时(n=8)或允许自主呼吸(SB)12小时(n=8)。另设急性麻醉组作为对照组(CON)(n=8)。安乐死后，观察大鼠的横隔肌收缩特性、纤维横截面积、蛋白分解(calain-1和caspase-3)和氧化应激(脂质过氧化、蛋白质氧化)。结果：在所有刺激频率下，SB组和MV组的横隔膜收缩力与对照组相比，差异无统计学意义。氧化应激指标和纤维横截面积在CON和SB/MV之间没有改变。MV组钙依赖性蛋白水解酶(calain-1和caspase-3)表达增强。七氟醚暴露后SB组和MV组p-AKT/AKT和p-FoxO1/FoxO1比值均显著低于对照组，且差异无统计学意义(P>0.05)。结论：七氟醚暴露不会引起氧化应激。这导致了隔膜力的降低。在MV组，七氟醚导致萎缩信号通路的激活。这些发现对重症监护病房的临床应用具有特别重要的意义，并对其使用提出质疑，特别是在SB阶段。
BACKGROUND: Ventilator-induced diaphragmatic dysfunction is associated with the generation of oxidative stress, enhanced proteolysis, autophagy and reduced protein synthesis in the diaphragm. Sevoflurane is a common operating room anesthetic and can be used in the intensive care medicine as well. Besides its anesthetic properties, its use in cardiac ischemia-reperfusion models can maintain protein synthesis and inhibit generation of reactive oxygen species, if used at the beginning of heart surgery. This study has been performed on the hypothesis that sevoflurane might protect against ventilator-induced diaphragmatic dysfunction by preventing the production of oxidative stress.METHODS: Four-month-old, male Sprague-Dawley rats sedated with sevoflurane (minimal alveolar concentration = 1) were either mechanically ventilated (MV) for 12 hours (n = 8) or allowed to breathe spontaneously (SB) for 12 hours (n = 8). An acutely anesthetized group was used as a control (Con) group (n = 8). After euthanization, diaphragmatic contractile properties, fiber cross-sectional areas, proteolysis (calpain-1 and caspase-3), and oxidative stress (lipid peroxidation, protein oxidation) were examined. After testing for normality, 1-way or 2-way analysis of variance with the Dunnett post hoc test was used to test for significance.RESULTS: The diaphragm contractile force was similarly reduced at all stimulation frequencies in the SB and MV groups compared with controls. Markers of oxidative stress and fiber cross-sectional areas were unaltered between Con and SB/MV, respectively. The calcium-dependent proteases (calpain-1 and caspase-3) were enhanced in the MV group. The p-AKT/AKT ratio and p-FoxO1/FoxO1 ratio were significantly and similarly reduced after sevoflurane exposure in the SB and MV group compared with Con group.CONCLUSIONS: Exposure to sevoflurane did not induce oxidative stress. It led to reduction in diaphragmatic force. In the MV group, sevoflurane led to the activation of atrophy signaling pathways. These findings are of particular importance for clinical utilization in intensive care units and question its use, especially during the phases of SB.