Diaphragm Atrophy and Weakness in the Absence of Mitochondrial Dysfunction in the Critically Ill
Diaphragm Atrophy and Weakness in the Absence of Mitochondrial Dysfunction in the Critically Ill
复制标题
DOI：
10.1164/rccm.201703-0501oc
复制
发表时间：
2017-12-15
影响因子：
24.7
通讯作者：
Ottenheijm, Coen A. C.
中科院分区：
文献类型：
--
作者：
van den Berg, Marloes;Hooijman, Pleuni E.;Ottenheijm, Coen A. C.
理由：危重患者膈肌无力的临床意义是显而易见的：它会延长呼吸机依赖时间，增加发病率、住院时间和医疗费用。膈肌无力的机制尚不清楚，但可能包括线粒体功能障碍和氧化应激。目的：我们假设危重患者的膈肌纤维无力伴随着线粒体功能和结构受损，以及氧化应激标志物增加。方法：为了检验这些假设，我们研究了收缩力， 线粒体功能和膈肌纤维中的线粒体结构。从 36 名机械通气重症患者的膈肌活检中分离出纤维，并与从 27 名疑似早期肺恶性肿瘤患者（对照受试者）的活检中分离出的纤维进行比较。测量和主要结果：危重患者的膈肌纤维表现出明显的萎缩和收缩无力，但没有线粒体呼吸受损和氧化应激水平增加 标记。尽管融合蛋白含量较低，但线粒体能量状态和形态没有改变。结论：危重患者在没有线粒体功能障碍和氧化应激的情况下，存在明显的膈肌纤维萎缩和无力。因此，线粒体功能障碍和氧化应激在危重患者膈肌萎缩和收缩无力的发展中不起因果作用。
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 and structure, and by 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 36 mechanically ventilated critically ill patients and compared with those isolated from biopsies of 27 patients with suspected early-stage lung malignancy (control subjects).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.