Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2017, Article ID 7897325, 12 pages
https://doi.org/10.1155/2017/7897325
Review Article

Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis

1Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Service de Réanimation Médicale, avenue Molière, 67098 Strasbourg Cedex, France
2Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Faculté de Médecine, Institut de Physiologie, Equipe d’Accueil 3072 “Mitochondrie, Stress Oxydant et Protection Musculaire”, 11 rue Human, 67000 Strasbourg, France
3Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Service d’Anesthésie-Réanimation Chirurgicale, avenue Molière, 67098 Strasbourg Cedex, France
4Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch, France
5Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Service de Physiologie et d’Explorations Fonctionnelles, 1 Place de l’Hôpital, 67091 Strasbourg Cedex, France

Correspondence should be addressed to Julien Pottecher; rf.gruobsarts-urhc@rehcettop.neiluj

Received 1 February 2017; Revised 16 March 2017; Accepted 23 April 2017; Published 15 May 2017

Academic Editor: Thomas Griffith

Copyright © 2017 Quentin Maestraggi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Singer, C. S. Deutschman, C. W. Seymour et al., “The third international consensus definitions for sepsis and septic shock (sepsis-3),” The Journal of the American Medical Association, vol. 315, no. 8, pp. 801–810, 2016. View at Publisher · View at Google Scholar
  2. R. C. Bone, R. A. Balk, F. B. Cerra et al., “Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine,” Chest, vol. 101, no. 6, pp. 1644–1655, 1992. View at Publisher · View at Google Scholar
  3. M. M. Levy, M. P. Fink, J. C. Marshall et al., “2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference,” Critical Care Medicine, vol. 31, no. 4, pp. 1250–1256, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Shankar-Hari, G. S. Phillips, M. L. Levy et al., “Developing a new definition and assessing new clinical criteria for septic shock,” The Journal of the American Medical Association, vol. 315, no. 8, pp. 775–787, 2016. View at Publisher · View at Google Scholar
  5. J.-L. Vincent, R. Moreno, J. Takala et al., “The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure,” Intensive Care Medicine, vol. 22, no. 7, pp. 707–710, 1996. View at Publisher · View at Google Scholar · View at Scopus
  6. R. J. Levy, “Mitochondrial dysfunction, bioenergetic impairment, and metabolic down-regulation in sepsis,” Shock, vol. 28, no. 1, pp. 24–28, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. E. Abraham and M. Singer, “Mechanisms of sepsis-induced organ dysfunction,” Critical Care Medicine, vol. 35, no. 10, pp. 2408–2416, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. R. S. Hotchkiss and I. E. Karl, “The pathophysiology and treatment of sepsis,” The New England Journal of Medicine, vol. 348, no. 2, pp. 138–150, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. E. Rivers, B. Nguyen, S. Havstad et al., “Early goal-directed therapy in the treatment of severe sepsis and septic shock,” The New England Journal of Medicine, vol. 345, no. 19, pp. 1368–1377, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. D. De Backer, D. O. Cortes, K. Donadello, and J.-L. Vincent, “Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock,” Virulence, vol. 5, no. 1, pp. 73–79, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. M. P. Fink, “Bench-to-bedside review: cytopathic hypoxia,” Critical Care, vol. 6, no. 6, pp. 491–499, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. I. Lee and M. Hüttemann, “Energy crisis: the role of oxidative phosphorylation in acute inflammation and sepsis,” Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1842, no. 9, pp. 1579–1586, 2014. View at Publisher · View at Google Scholar · View at Scopus
  13. D. Brealey, S. Karyampudi, T. S. Jacques et al., “Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 286, no. 3, pp. R491–R497, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. B. B. Peruchi, F. Petronilho, H. A. Rojas et al., “Skeletal muscle electron transport chain dysfunction after sepsis in rats,” Journal of Surgical Research, vol. 167, no. 2, pp. e333–e338, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. L. A. Callahan and G. S. Supinski, “Sepsis-induced myopathy,” Critical Care Medicine, vol. 37, no. 10, pp. S354–S367, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. G. Garrabou, C. Morén, S. López et al., “The effects of sepsis on mitochondria,” Journal of Infectious Diseases, vol. 205, no. 3, pp. 392–400, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Hüttemann, S. Helling, T. H. Sanderson et al., “Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation,” Biochimica et Biophysica Acta, vol. 1817, no. 4, pp. 598–609, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Richter, V. Gogvadze, R. Laffranchi et al., “Oxidants in mitochondria: from physiology to diseases,” Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1271, no. 1, pp. 67–74, 1995. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Lejay, F. Fang, R. John et al., “Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus,” Journal of Molecular and Cellular Cardiology, vol. 91, pp. 11–22, 2016. View at Publisher · View at Google Scholar
  20. H. F. Galley, “Oxidative stress and mitochondrial dysfunction in sepsis,” British Journal of Anaesthesia, vol. 107, no. 1, pp. 57–64, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. J. M. Matés, C. Pérez-Gómez, and I. N. de Castro, “Antioxidant enzymes and human diseases,” Clinical Biochemistry, vol. 32, no. 8, pp. 595–603, 1999. View at Publisher · View at Google Scholar
  22. I. Manoli, S. Alesci, M. R. Blackman, Y. A. Su, O. M. Rennert, and G. P. Chrousos, “Mitochondria as key components of the stress response,” Trends in Endocrinology and Metabolism, vol. 18, no. 5, pp. 190–198, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. T. F. Liu, C. M. Brown, M. E. Gazzar et al., “Fueling the flame: bioenergy couples metabolism and inflammation,” Journal of Leukocyte Biology, vol. 92, no. 3, pp. 499–507, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. C. A. Piantadosi and H. B. Suliman, “Transcriptional control of mitochondrial biogenesis and its interface with inflammatory processes,” Biochimica et Biophysica Acta, vol. 1820, no. 4, pp. 532–541, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. M. R. Duchen, “Mitochondria in health and disease: perspectives on a new mitochondrial biology,” Molecular Aspects of Medicine, vol. 25, no. 4, pp. 365–451, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Javadov and M. Karmazyn, “Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection,” Cellular Physiology and Biochemistry, vol. 20, no. 1–4, pp. 1–22, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Lejay, A. Meyer, A.-I. Schlagowski et al., “Mitochondria: mitochondrial participation in ischemia-reperfusion injury in skeletal muscle,” The International Journal of Biochemistry & Cell Biology, vol. 50, pp. 101–105, 2014. View at Publisher · View at Google Scholar
  28. C. F. Wenceslau, C. G. McCarthy, T. Szasz, K. Spitler, S. Goulopoulou, and R. C. Webb, “Mitochondrial damage-associated molecular patterns and vascular function,” European Heart Journal, vol. 35, no. 18, pp. 1172–1177, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Quoilin, A. Mouithys-Mickalad, S. Lécart, M.-P. Fontaine-Aupart, and M. Hoebeke, “Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury,” Biochimica et Biophysica Acta, vol. 1837, no. 10, pp. 1790–1800, 2014. View at Publisher · View at Google Scholar
  30. S. Moncada and J. D. Erusalimsky, “Does nitric oxide modulate mitochondrial energy generation and apoptosis?” Nature Reviews Molecular Cell Biology, vol. 3, no. 3, pp. 214–220, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. B. Beltrán, A. Orsi, E. Clementi, and S. Moncada, “Oxidative stress and S-nitrosylation of proteins in cells,” British Journal of Pharmacology, vol. 129, no. 5, pp. 953–960, 2000. View at Publisher · View at Google Scholar · View at Scopus
  32. S. W. Ballinger, C. Patterson, C.-N. Yan et al., “Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells,” Circulation Research, vol. 86, no. 9, pp. 960–966, 2000. View at Publisher · View at Google Scholar · View at Scopus
  33. P. T. Schumacker, M. N. Gillespie, K. Nakahira et al., “Mitochondria in lung biology and pathology: more than just a powerhouse,” American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 306, no. 11, pp. L962–L974, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. J. L. Kuck, B. O. Obiako, O. M. Gorodnya et al., “Mitochondrial DNA damage-associated molecular patterns mediate a feedforward cycle of bacteria-induced vascular injury in perfused rat lungs,” American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 308, no. 10, pp. L1078–L1085, 2015. View at Publisher · View at Google Scholar · View at Scopus
  35. A. P. West, G. S. Shadel, and S. Ghosh, “Mitochondria in innate immune responses,” Nature Reviews Immunology, vol. 11, no. 6, pp. 389–402, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. C. S. Calfee and M. A. Matthay, “Clinical immunology: culprits with evolutionary ties,” Nature, vol. 464, no. 7285, pp. 41-42, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. A. D. Cherry, H. B. Suliman, R. R. Bartz, and C. A. Piantadosi, “Peroxisome proliferator-activated receptor γ co-activator 1-α as a critical co-activator of the murine hepatic oxidative stress response and mitochondrial biogenesis in Staphylococcus aureus sepsis,” Journal of Biological Chemistry, vol. 289, no. 1, pp. 41–52, 2014. View at Publisher · View at Google Scholar · View at Scopus
  38. N. K. Patil, N. Parajuli, L. A. MacMillan-Crow, and P. R. Mayeux, “Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury,” American Journal of Physiology—Renal Physiology, vol. 306, no. 7, pp. F734–F743, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Choumar, A. Tarhuni, P. Lettéron et al., “Lipopolysaccharide-induced mitochondrial DNA depletion,” Antioxidants and Redox Signaling, vol. 15, no. 11, pp. 2837–2854, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. R. S. Hotchkiss, A. Strasser, J. E. McDunn, and P. E. Swanson, “Cell death,” The New England Journal of Medicine, vol. 361, no. 16, pp. 1570–1583, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Singer, “Mitochondrial function in sepsis: acute phase versus multiple organ failure,” Critical Care Medicine, vol. 35, no. 9, pp. S441–S448, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Boulos, M. E. Astiz, R. S. Barua, and M. Osman, “Impaired mitochondrial function induced by serum from septic shock patients is attenuated by inhibition of nitric oxide synthase and poly(ADP-ribose) synthase,” Critical Care Medicine, vol. 31, no. 2, pp. 353–358, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. D. Brealey, M. Brand, I. Hargreaves et al., “Association between mitochondrial dysfunction and severity and outcome of septic shock,” The Lancet, vol. 360, no. 9328, pp. 219–223, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. C. C. Dahm, K. Moore, and M. P. Murphy, “Persistent S-nitrosation of complex I and other mitochondrial membrane proteins by S-nitrosothiols but not nitric oxide or peroxynitrite: Implications for the interaction of nitric oxide with mitochondria,” Journal of Biological Chemistry, vol. 281, no. 15, pp. 10056–10065, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. G. C. Brown and V. Borutaite, “Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols,” Biochimica et Biophysica Acta—Bioenergetics, vol. 1658, no. 1-2, pp. 44–49, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. E. Nisoli and M. O. Carruba, “Nitric oxide and mitochondrial biogenesis,” Journal of Cell Science, vol. 119, no. 14, pp. 2855–2862, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. R. R. Bartz, P. Fu, H. B. Suliman et al., “Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice,” PLoS ONE, vol. 9, no. 7, Article ID e100912, 2014. View at Publisher · View at Google Scholar · View at Scopus
  48. J. M. Cuesta and M. Singer, “The stress response and critical illness: a review,” Critical Care Medicine, vol. 40, no. 12, pp. 3283–3289, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. S. V. Baudouin, D. Saunders, W. Tiangyou et al., “Mitochondrial DNA and survival after sepsis: a prospective study,” The Lancet, vol. 366, no. 9503, pp. 2118–2121, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. J. E. Carré, J.-C. Orban, L. Re et al., “Survival in critical illness is associated with early activation of mitochondrial biogenesis,” American Journal of Respiratory and Critical Care Medicine, vol. 182, no. 6, pp. 745–751, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. O. Friedrich, M. B. Reid, G. Van Den Berghe et al., “The sick and the weak: neuropathies/ myopathies in the critically ill,” Physiological Reviews, vol. 95, no. 3, article no. A09, pp. 1025–1109, 2015. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Batt, C. C. Dos Santos, J. I. Cameron, and M. S. Herridge, “Intensive care unit-acquired weakness clinical phenotypes and molecular mechanisms,” American Journal of Respiratory and Critical Care Medicine, vol. 187, no. 3, pp. 238–246, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Batt, M. Herridge, and C. dos Santos, “Mechanism of ICU-acquired weakness: skeletal muscle loss in critical illness,” Intensive Care Medicine, vol. 187, no. 10, p. 238, 2017. View at Publisher · View at Google Scholar
  54. A. Demoule, B. Jung, H. Prodanovic et al., “Diaphragm dysfunction on admission to the intensive care unit: prevalence, risk factors, and prognostic impact—a prospective study,” American Journal of Respiratory and Critical Care Medicine, vol. 188, no. 2, pp. 213–219, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. N. A. Ali, J. M. O'Brien Jr., S. P. Hoffmann et al., “Acquired weakness, handgrip strength, and mortality in critically III patients,” American Journal of Respiratory and Critical Care Medicine, vol. 178, no. 3, pp. 261–268, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. T. J. Iwashyna, E. W. Ely, D. M. Smith, and K. M. Langa, “Long-term cognitive impairment and functional disability among survivors of severe sepsis,” JAMA—Journal of the American Medical Association, vol. 304, no. 16, pp. 1787–1794, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. P. S. Zolfaghari, J. E. Carré, N. Parker, N. A. Curtin, M. R. Duchen, and M. Singer, “Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis,” American Journal of Physiology—Endocrinology and Metabolism, vol. 308, no. 9, pp. E713–E725, 2015. View at Publisher · View at Google Scholar · View at Scopus
  58. S. K. Powers, A. N. Kavazis, and S. Levine, “Prolonged mechanical ventilation alters diaphragmatic structure and function,” Critical Care Medicine, vol. 37, no. 10, pp. S347–S353, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. N. Bernard, S. Matecki, G. Py, S. Lopez, J. Mercier, and X. Capdevila, “Effects of prolonged mechanical ventilation on respiratory muscle ultrastructure and mitochondrial respiration in rabbits,” Intensive Care Medicine, vol. 29, no. 1, pp. 111–118, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. M. Picard, B. Jung, F. Liang et al., “Mitochondrial dysfunction and lipid accumulation in the human diaphragm during mechanical ventilation,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 11, pp. 1140–1149, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. M. Mofarrahi, I. Sigala, Y. Guo et al., “Autophagy and skeletal muscles in sepsis,” PLoS ONE, vol. 7, no. 10, Article ID e47265, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. C. E. Baldwin and A. D. Bersten, “Alterations in respiratory and limb muscle strength and size in patients with sepsis who are mechanically ventilated,” Physical Therapy, vol. 94, no. 1, pp. 68–82, 2014. View at Publisher · View at Google Scholar · View at Scopus
  63. A. H. V. Remels, H. R. Gosker, P. Schrauwen et al., “TNF-α impairs regulation of muscle oxidative phenotype: implications for cachexia?” FASEB Journal, vol. 24, no. 12, pp. 5052–5062, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. H. W. H. van Hees, W.-J. M.-J. Schellekens, M. Linkels et al., “Plasma from septic shock patients induces loss of muscle protein,” Critical Care, vol. 15, no. 5, article R233, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. B. Lebas, J. Pottecher, A. L. Charles et al., “Skeletal muscle mitochondrial dysfunction after short-term septic shock,” Acta Physiologica, vol. 214, pp. 63–63, 2015. View at Publisher · View at Google Scholar
  66. J. Grip, T. Jakobsson, N. Tardif, and O. Rooyackers, “The effect of plasma from septic ICU patients on healthy rat muscle mitochondria,” Intensive Care Medicine Experimental, pp. 1–8, 2016. View at Publisher · View at Google Scholar
  67. K. Jiroutková, A. Krajčová, J. Ziak et al., “Mitochondrial function in skeletal muscle of patients with protracted critical illness and ICU-acquired weakness,” Critical Care, vol. 19, no. 1, article 448, 2015. View at Publisher · View at Google Scholar · View at Scopus
  68. V. Jeger, S. Djafarzadeh, S. M. Jakob, and J. Takala, “Mitochondrial function in sepsis,” European Journal of Clinical Investigation, vol. 43, no. 5, pp. 532–542, 2013. View at Publisher · View at Google Scholar · View at Scopus
  69. C. R. Brinkmann, L. Jensen, F. Dagnæs-Hansen et al., “Mitochondria and the lectin pathway of complement,” Journal of Biological Chemistry, vol. 288, no. 12, pp. 8016–8027, 2013. View at Publisher · View at Google Scholar · View at Scopus
  70. K. Timmermans, M. Kox, G. J. Scheffer, and P. Pickkers, “Plasma nuclear and mitochondrial DNA levels, and markers of inflammation, shock, and organ damage in patients with septic shock,” Shock, vol. 45, no. 6, pp. 607–612, 2016. View at Publisher · View at Google Scholar · View at Scopus
  71. D. W. Haden, H. B. Suliman, M. S. Carraway et al., “Mitochondrial biogenesis restores oxidative metabolism during Staphylococcus aureus sepsis,” American Journal of Respiratory and Critical Care Medicine, vol. 176, no. 8, pp. 768–777, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. R. S. Hotchkiss, K. W. Tinsley, P. E. Swanson et al., “Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans,” Journal of Immunology, vol. 166, no. 11, pp. 6952–6963, 2001. View at Publisher · View at Google Scholar · View at Scopus
  73. D. H. Wyllie, I. C. J. W. Bowler, and T. E. A. Peto, “Relation between lymphopenia and bacteraemia in UK adults with medical emergencies,” Journal of Clinical Pathology, vol. 57, no. 9, pp. 950–955, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. D. C. Angus and T. van der Poll, “Severe sepsis and septic shock,” The New England Journal of Medicine, vol. 369, no. 9, pp. 840–851, 2013. View at Publisher · View at Google Scholar · View at Scopus
  75. J. S. Boomer, K. To, K. C. Chang et al., “Immunosuppression in patients who die of sepsis and multiple organ failure,” Journal of the American Medical Association, vol. 306, no. 23, pp. 2594–2605, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. K. C. Chang, J. Unsinger, C. G. Davis et al., “Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis,” FASEB Journal, vol. 21, no. 3, pp. 708–719, 2007. View at Publisher · View at Google Scholar · View at Scopus
  77. Z.-G. Liu, S.-Y. Ni, G.-M. Chen et al., “Histones-mediated lymphocyte apoptosis during sepsis is dependent on p38 phosphorylation and mitochondrial permeability transition,” PLoS ONE, vol. 8, no. 10, Article ID e77131, 2013. View at Publisher · View at Google Scholar · View at Scopus
  78. S. U. Weber, J.-C. Schewe, L. E. Lehmann et al., “Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis,” Critical Care, vol. 12, no. 5, article R128, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. P. Bilbault, T. Lavaux, A. Launoy et al., “Influence of drotrecogin alpha (activated) infusion on the variation of Bax/Bcl-2 and Bax/Bcl-xl ratios in circulating mononuclear cells: a cohort study in septic shock patients,” Critical Care Medicine, vol. 35, no. 1, pp. 69–75, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. A. M. Japiassú, A. P. S. A. Santiago, J. D. C. P. D'Avila et al., “Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5′-triphosphate synthase activity,” Critical Care Medicine, vol. 39, no. 5, pp. 1056–1063, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. I. Belikova, A. C. Lukaszewicz, V. Faivre, C. Damoisel, M. Singer, and D. Payen, “Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis,” Critical Care Medicine, vol. 35, no. 12, pp. 2702–2708, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Singer, “The role of mitochondrial dysfunction in sepsis-induced multi-organ failure,” Virulence, vol. 5, no. 1, pp. 66–72, 2014. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Sun, T. Sursal, Y. Adibnia et al., “Mitochondrial DAMPs Increase Endothelial Permeability through neutrophil dependent and independent pathways,” PLoS ONE, vol. 8, no. 3, Article ID e59989, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. K. Timmermans, M. Kox, M. Vaneker et al., “Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients,” Intensive Care Medicine, vol. 42, no. 4, pp. 551–561, 2016. View at Publisher · View at Google Scholar · View at Scopus
  85. S. L. Weiss, M. A. Selak, F. Tuluc et al., “Mitochondrial dysfunction in peripheral blood mononuclear cells in pediatric septic shock,” Pediatric Critical Care Medicine, vol. 16, no. 1, pp. e4–e12, 2015. View at Publisher · View at Google Scholar · View at Scopus
  86. F. Sjövall, S. Morota, J. Persson, M. J. Hansson, and E. Elmér, “Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells,” Critical Care, vol. 17, no. 4, article R152, 2013. View at Publisher · View at Google Scholar · View at Scopus
  87. G. J. W. van der Windt, B. Everts, C.-H. Chang et al., “Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development,” Immunity, vol. 36, no. 1, pp. 68–78, 2012. View at Publisher · View at Google Scholar · View at Scopus
  88. O. Peñuelas, F. Frutos-Vivar, C. Fernández et al., “Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation,” American Journal of Respiratory and Critical Care Medicine, vol. 184, no. 4, pp. 430–437, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. M. Macht, T. Wimbish, C. Bodine, and M. Moss, “ICU-acquired swallowing disorders,” Critical Care Medicine, vol. 41, no. 10, pp. 2396–2405, 2013. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Macht, T. Wimbish, B. J. Clark et al., “Post-extubation dysphagia is persistent and associated with poor outcomes in survivors of critical illness,” Critical Care, vol. 15, no. 5, p. R231, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. A. Drewry, N. Samra, L. Skrupky, B. Fuller, S. Compton, and R. Hotchkiss, “Persistent lymphopenia after diagnosis of sepsis predicts mortality,” Shock, vol. 42, no. 5, pp. 383–391, 2014. View at Publisher · View at Google Scholar · View at Scopus
  92. R. S. Hotchkiss, G. Monneret, and D. Payen, “Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy,” Nature Reviews Immunology, vol. 13, no. 12, pp. 862–874, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. D. Annane, E. Bellissant, and J. Cavaillon, “Septic shock,” The Lancet, vol. 365, no. 9453, pp. 63–78, 2005. View at Publisher · View at Google Scholar
  94. E. P. Rivers, J. A. Kruse, G. Jacobsen et al., “The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock,” Critical Care Medicine, vol. 35, no. 9, pp. 2016–2024, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. ProCESS, D. M. Yealy, J. A. Kellum et al., “A randomized trial of protocol-based care for early septic shock,” The New England Journal of Medicine, vol. 370, no. 18, pp. 1683–1693, 2014. View at Publisher · View at Google Scholar · View at Scopus
  96. D. M. Rosser, R. P. Stidwill, D. Jacobson, and M. Singer, “Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis,” Journal of Applied Physiology, vol. 79, no. 6, pp. 1878–1882, 1995. View at Google Scholar · View at Scopus
  97. P. Boekstegers, S. Weidenhofer, T. Kapsner, and K. Werdan, “Skeletal muscle partial pressure of oxygen in patients with sepsis,” Critical Care Medicine, vol. 22, no. 4, pp. 640–650, 1994. View at Publisher · View at Google Scholar · View at Scopus
  98. T. D. Corrêa, M. Vuda, A. R. Blaser et al., “Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis,” Critical Care Medicine, vol. 40, no. 10, pp. 2841–2849, 2012. View at Publisher · View at Google Scholar · View at Scopus
  99. T. Regueira, B. Bänziger, S. Djafarzadeh et al., “Norepinephrine to increase blood pressure in endotoxaemic pigs is associated with improved hepatic mitochondrial respiration,” Critical Care, vol. 12, no. 4, article R88, 2008. View at Publisher · View at Google Scholar · View at Scopus
  100. A. Protti, J. Carré, M. T. Frost et al., “Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle,” Critical Care Medicine, vol. 35, no. 9, pp. 2150–2155, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. A. J. Dare, A. R. J. Phillips, A. J. R. Hickey et al., “A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome,” Free Radical Biology and Medicine, vol. 47, no. 11, pp. 1517–1525, 2009. View at Publisher · View at Google Scholar · View at Scopus
  102. S. Dal-Ros, J. Zoll, A.-L. Lang et al., “Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: role of NADPH oxidase,” Biochemical and Biophysical Research Communications, vol. 404, no. 2, pp. 743–749, 2011. View at Publisher · View at Google Scholar · View at Scopus
  103. J. Morel and M. Singer, “Statins, fibrates, thiazolidinediones and resveratrol as adjunctive therapies in sepsis: could mitochondria be a common target?” Intensive Care Medicine Experimental, vol. 2, no. 1, pp. 1–9, 2014. View at Publisher · View at Google Scholar
  104. M. Lagouge, C. Argmann, Z. Gerhart-Hines et al., “Resveratrol improves mitochondrial function and protects against metabolicdisease by activating SIRT1 and PGC-1α,” Cell, vol. 127, no. 6, pp. 1109–1122, 2006. View at Publisher · View at Google Scholar · View at Scopus
  105. G. Escames, L. C. López, V. Tapias et al., “Melatonin counteracts inducible mitochondrial nitric oxide synthase-dependent mitochondrial dysfunction in skeletal muscle of septic mice,” Journal of Pineal Research, vol. 40, no. 1, pp. 71–78, 2006. View at Publisher · View at Google Scholar · View at Scopus
  106. P. Bullón, L. Román-Malo, F. Marín-Aguilar et al., “Lipophilic antioxidants prevent lipopolysaccharide-induced mitochondrial dysfunction through mitochondrial biogenesis improvement,” Pharmacological Research, vol. 91, pp. 1–8, 2015. View at Publisher · View at Google Scholar · View at Scopus
  107. Q. S. Zang, H. Sadek, D. L. Maass et al., “Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 302, no. 9, pp. H1847–H1859, 2012. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Leone and R. Moreau, “Leukocyte toll-Like receptor 2-mitochondria axis in sepsis: unraveling immune response sophistication,” Anesthesiology, vol. 121, no. 6, pp. 1147–1149, 2014. View at Publisher · View at Google Scholar · View at Scopus