RATIONALE: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency, and increases morbidity, duration of hospital stay and health care costs. The mechanisms underlying diaphragm weakness are unknown, but might include mitochondrial dysfunction and oxidative stress. OBJECTIVES: We hypothesized that weakness of diaphragm muscle fibers in critically ill patients is accompanied by impaired mitochondrial function, structure, and increased markers of oxidative stress. METHODS: To test these hypotheses, we studied contractile force, mitochondrial function, and mitochondrial structure in diaphragm muscle fibers. Fibers were isolated from diaphragm biopsies of thirty-six mechanically ventilated critically ill patients and compared to those isolated from biopsies of twenty-seven patients with suspected early-stage lung malignancy (controls). MEASUREMENTS AND MAIN RESULTS: Diaphragm muscle fibers from critically ill patients displayed significant atrophy and contractile weakness, but lacked impaired mitochondrial respiration and increased levels of oxidative stress markers. Mitochondrial energy status and morphology were not altered, despite a lower content of fusion proteins. CONCLUSIONS: Critically ill patients have manifest diaphragm muscle fiber atrophy and weakness, in the absence of mitochondrial dysfunction and oxidative stress. Thus, mitochondrial dysfunction and oxidative stress do not play a causative role in the development of atrophy and contractile weakness of the diaphragm in critically ill patients.

中文翻译：

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严重疾病中缺乏线粒体功能障碍的肌萎缩和虚弱

理由：重症患者diaphragm肌无力的临床意义是显而易见的：它延长了对呼吸机的依赖，并增加了发病率，住院时间和医疗保健费用。diaphragm肌无力的潜在机制尚不清楚，但可能包括线粒体功能障碍和氧化应激。目的：我们假设重症患者的diaphragm肌肌纤维无力伴随着线粒体功能，结构和氧化应激标志物的受损。方法：为了检验这些假设，我们研究了diaphragm肌纤维中的收缩力，线粒体功能和线粒体结构。从36例机械通气危重患者的隔膜活检中分离出纤维，并与从27例怀疑为早期肺恶性肿瘤的患者（对照）的活检中分离出的纤维进行了比较。测量和主要结果：重症患者的Dia肌纤维表现出明显的萎缩和收缩无力，但缺乏线粒体呼吸功能受损和氧化应激标志物水平升高。尽管融合蛋白的含量较低，但线粒体的能量状态和形态没有改变。结论：在没有线粒体功能障碍和氧化应激的情况下，重症患者表现为diaphragm肌纤维萎缩和无力。因此，