Diaphragm Atrophy and Weakness in the Absence of Mitochondrial Dysfunction in the Critically Ill

被引:54
作者
van den Berg, Marloes [1 ]
Hooijman, Pleuni E. [1 ]
Beishuizen, Albertus [4 ]
de Waard, Monique C. [2 ]
Paul, Marinus A. [3 ]
Hartemink, Koen J. [5 ]
van Hees, Hieronymus W. H. [6 ]
Lawlor, Michael W. [7 ]
Brocca, Lorenza [8 ]
Bottinelli, Roberto [8 ,9 ,11 ]
Pellegrino, Maria A. [8 ,9 ,10 ]
Stienen, Ger J. M. [1 ,12 ]
Heunks, Leo M. A. [2 ]
Wust, Rob C. I. [1 ,13 ]
Ottenheijm, Coen A. C. [1 ,14 ]
机构
[1] Vrije Univ, Univ Med Ctr, Amsterdam Cardiovasc Sci, Dept Physiol, Amsterdam, Netherlands
[2] Vrije Univ, Univ Med Ctr, Dept Intens Care, Amsterdam, Netherlands
[3] Vrije Univ, Univ Med Ctr, Dept Cardiothorac Surg, Amsterdam, Netherlands
[4] Med Spectrum Twente, Dept Intens Care, Enschede, Netherlands
[5] Netherlands Canc Inst, Dept Surg, Antoni von Leeuwenhoek Hosp, Amsterdam, Netherlands
[6] Radboud Univ Nijmegen, Med Ctr, Dept Pulmonol, Nijmegen, Netherlands
[7] Med Coll Wisconsin, Div Pediat Pathol, Milwaukee, WI 53226 USA
[8] Univ Pavia, Dept Mol Med, Pavia, Italy
[9] Univ Pavia, Interdept Ctr Biol & Sport Med, Pavia, Italy
[10] Univ Pavia, Interuniv Inst Myol, Pavia, Italy
[11] Fdn Salvatore Maugeri IRCCS, Sci Inst Pavia, Pavia, Italy
[12] Vrije Univ Amsterdam, Dept Phys & Astron, Fac Sci, Amsterdam, Netherlands
[13] Acad Med Ctr, Lab Genet Metab Dis, Amsterdam, Netherlands
[14] Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ USA
关键词
mechanical ventilation; critically ill; diaphragm weakness; mitochondrial dysfunction; oxidative stress; INTENSIVE-CARE-UNIT; PHRENIC-NERVE STIMULATION; HINDLIMB-UNLOADED MICE; MECHANICAL VENTILATION; OXIDATIVE STRESS; SKELETAL-MUSCLE; INSULIN-RESISTANCE; OVER-EXPRESSION; ORGAN DONOR; FUSION;
D O I
10.1164/rccm.201703-0501OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
引用
收藏
页码:1544 / 1558
页数:15
相关论文
共 55 条
[1]   Cigarette smoke-induced oxidative stress in skeletal muscles of mice [J].
Barreiro, Esther ;
del Puerto-Nevado, Laura ;
Puig-Vilanova, Ester ;
Perez-Rial, Sandra ;
Sanchez, Francisco ;
Martinez-Galan, Lourdes ;
Rivera, Stephanie ;
Gea, Joaquim ;
Gonzalez-Mangado, Nicolas ;
Peces-Barba, German .
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 2012, 182 (01) :9-17
[2]   Is oxidative stress a cause or consequence of disuse muscle atrophy in mice? A proteomic approach in hindlimb-unloaded mice [J].
Brocca, Lorenza ;
Pellegrino, Maria Antonietta ;
Desaphy, Jean-Francois ;
Pierno, Sabata ;
Camerino, Diana Conte ;
Bottinelli, Roberto .
EXPERIMENTAL PHYSIOLOGY, 2010, 95 (02) :331-350
[3]   The role of alterations in mitochondrial dynamics and PGC-1α over-expression in fast muscle atrophy following hindlimb unloading [J].
Cannavino, Jessica ;
Brocca, Lorenza ;
Sandri, Marco ;
Grassi, Bruno ;
Bottinelli, Roberto ;
Pellegrino, Maria Antonietta .
JOURNAL OF PHYSIOLOGY-LONDON, 2015, 593 (08) :1981-1995
[4]   PGC1-α over-expression prevents metabolic alterations and soleus muscle atrophy in hindlimb unloaded mice [J].
Cannavino, Jessica ;
Brocca, Lorenza ;
Sandri, Marco ;
Bottinelli, Roberto ;
Pellegrino, Maria Antonietta .
JOURNAL OF PHYSIOLOGY-LONDON, 2014, 592 (20) :4575-4589
[5]   Fusion and Fission: Interlinked Processes Critical for Mitochondrial Health [J].
Chan, David C. .
ANNUAL REVIEW OF GENETICS, VOL 46, 2012, 46 :265-287
[6]   Disruption of fusion results in mitochondrial heterogeneity and dysfunction [J].
Chen, HC ;
Chomyn, A ;
Chan, DC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (28) :26185-26192
[7]   Mitochondrial Fusion Is Required for mtDNA Stability in Skeletal Muscle and Tolerance of mtDNA Mutations [J].
Chen, Hsiuchen ;
Vermulst, Marc ;
Wang, Yun E. ;
Chomyn, Anne ;
Prolla, Tomas A. ;
McCaffery, J. Michael ;
Chan, David C. .
CELL, 2010, 141 (02) :280-289
[8]   Diaphragm Dysfunction on Admission to the Intensive Care Unit Prevalence, Risk Factors, and Prognostic Impact-A Prospective Study [J].
Demoule, Alexandre ;
Jung, Boris ;
Prodanovic, Helene ;
Molinari, Nicolas ;
Chanques, Gerald ;
Coirault, Catherine ;
Matecki, Stefan ;
Duguet, Alexandre ;
Similowski, Thomas ;
Jaber, Samir .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2013, 188 (02) :213-219
[9]   Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients [J].
Dres, Martin ;
Dube, Bruno-Pierre ;
Mayaux, Julien ;
Delemazure, Julie ;
Reuter, Danielle ;
Brochard, Laurent ;
Similowski, Thomas ;
Demoule, Alexandre .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2017, 195 (01) :57-66
[10]   Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio [J].
Emerling, Brooke M. ;
Weinberg, Frank ;
Snyder, Colleen ;
Burgess, Zach ;
Mutlu, Goekhan M. ;
Viollet, Benoit ;
Budinger, G. R. Scott ;
Chandel, Navdeep S. .
FREE RADICAL BIOLOGY AND MEDICINE, 2009, 46 (10) :1386-1391