Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production.
Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production.
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DOI：
10.1016/j.freeradbiomed.2009.01.002
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发表时间：
2009-03-15
影响因子：
7.4
通讯作者：
Powers, Scott K.
中科院分区：
文献类型：
--
作者：
Kavazis, Andreas N.;Talbert, Erin E.;Smuder, Ashley J.;Hudson, Matthew B.;Nelson, W. Bradley;Powers, Scott K.
机械通气(MV)是一种用于急性呼吸衰竭患者的救命干预措施。不幸的是，机械通气时间过长会导致横隔肌无力，这是导致患者无法脱离机械通气的一个重要原因。我们的实验室先前已经证明，活性氧(ROS)在介导MV后的横隔肌无力中起着关键作用。然而，MV诱导的横隔膜ROS产生的途径仍不清楚。这些实验验证了延长机械通气会导致线粒体ROS释放增加、线粒体氧化损伤和线粒体功能障碍的假说。为了验证这一假设，成年(3-4月龄)雌性SD大鼠被分配到对照组或12小时机械通气组。治疗结束后，去除横隔膜，分离线粒体，用于随后的呼吸和生化测量。与对照组相比，机械通气时间延长导致膜线粒体呼吸控制率降低。此外，MV动物的横隔膜线粒体在状态3和状态4呼吸中都释放了更高的ROS速率。延长的MV也与隔膜线粒体的氧化损伤有关，这表明脂质过氧化和蛋白质氧化增加。最后，我们的数据还显示，在MV动物横隔膜分离的线粒体中，电子传输链复合体II、III和IV的活性受到抑制。总之，这些结果与横隔膜不活动促进线粒体ROS释放增加、线粒体氧化损伤和线粒体呼吸功能障碍的概念是一致的。
Mechanical ventilation (MV) is a life-saving intervention used in patients with acute respiratory failure. Unfortunately, prolonged MV results in diaphragmatic weakness, which is an important contributor to the failure to wean patients from MV. Our laboratory has previously shown that reactive oxygen species (ROS) play a critical role in mediating diaphragmatic weakness after MV. However, the pathways responsible for MV-induced diaphragmatic ROS production remain unknown. These experiments tested the hypothesis that prolonged MV results in an increase in mitochondrial ROS release, mitochondrial oxidative damage, and mitochondrial dysfunction. To test this hypothesis, adult (3–4 months of age) female Sprague–Dawley rats were assigned to either a control or a 12-h MV group. After treatment, diaphragms were removed and mitochondria were isolated for subsequent respiratory and biochemical measurements. Compared to control, prolonged MV resulted in a lower respiratory control ratio in diaphragmatic mitochondria. Furthermore, diaphragmatic mitochondria from MV animals released higher rates of ROS in both State 3 and State 4 respiration. Prolonged MV was also associated with diaphragmatic mitochondrial oxidative damage as indicated by increased lipid peroxidation and protein oxidation. Finally, our data also reveal that the activities of the electron transport chain complexes II, III, and IV are depressed in mitochondria isolated from diaphragms of MV animals. In conclusion, these results are consistent with the concept that diaphragmatic inactivity promotes an increase in mitochondrial ROS emission, mitochondrial oxidative damage, and mitochondrial respiratory dysfunction.
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影响因子：
3.3
作者：
Falk, D. J.;DeRuisseau, K. C.;Powers, S. K.
通讯作者：
Powers, S. K.
DOI：
10.1164/rccm.200601-142oc
发表时间：
2007-01-15
影响因子：
24.7
作者：
McClung, Joseph M.;Kavazis, Andreas N.;Powers, Scott K.
通讯作者：
Powers, Scott K.
影响因子：
3.3
作者：
DeRuisseau, KC;Kavazis, AN;Powers, SK
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影响因子：
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作者：
Moghaddas, S;Hoppel, CL;Lesnefsky, EJ
通讯作者：
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影响因子：
7.4
作者：
Lawler, JM;Song, W;Demaree, SR
通讯作者：
Demaree, SR