• Marloes van den Berg, Pleuni E Hooijman, Albertus Beishuizen, Monique C de Waard, Marinus A Paul, Koen J Hartemink, van Hees Hieronymus W H HWH 6 Department of Pulmonology, Radboud University Medical Center, Nijmegen, the Netherlands., Michael W Lawlor, Lorenza Brocca, Roberto Bottinelli, Maria A Pellegrino, Stienen Ger J M GJM 1 Department of Physiology, Amsterdam Cardiovascular Sciences. 12 Faculty of Science, Heunks Leo M A LMA 3 Department of Intensive Care, and., Rob C I Wüst, and Ottenheijm Coen A C CAC 1 Department of Physiology, Amsterdam Cardiovascular Sciences. 14 Department of .
• 1 Department of Physiology, Amsterdam Cardiovascular Sciences.
• Am. J. Respir. Crit. Care Med. 2017 Dec 15; 196 (12): 1544-1558.

RationaleThe 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.ObjectivesWe 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.MethodsTo 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 ResultsDiaphragm 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.ConclusionsCritically 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.

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