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Mitochondrial Function in Septic Shock

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Annual Update in Intensive Care and Emergency Medicine 2011

Part of the book series: Annual Update in Intensive Care and Emergency Medicine 2011 ((AUICEM,volume 1))

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Abstract

Shock is the result of failure of the circulatory system to adequately deliver oxygen and nutrients to tissues. At the bedside, the clinician synthesizes data from the history, signs of hypoperfusion on physical exam, vital signs and urine output, and laboratory markers of the adequacy of substrate provision to determine the presence of shock. However, prior to the onset of clinically evident shock, the insult is first experienced at a subcellular level by the mitochondria, leading to their description as “canaries in a coal mine” [1]. Ultimately, shock is the result of failure of adequate oxygen delivery (DO2) and utilization within mitochondria, which collectively are responsible for nearly all the oxygen consumption and energy production in the body.

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References

  1. Williams RS (2000) Canaries in the coal mine: mitochondrial DNA and vascular injury from reactive oxygen species. Circ Res 86: 915–916

    PubMed  CAS  Google Scholar 

  2. Jones AE, Brown MD, Trzeciak S, et al (2008) The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis. Crit Care Med 36: 2734–2739

    Article  PubMed  Google Scholar 

  3. Levy RJ (2007) Mitochondrial dysfunction, bioenergenic impairment, and metabolic down-regulation in sepsis. Shock 28: 24–28

    Article  PubMed  CAS  Google Scholar 

  4. De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL (2002) Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 166: 98–104

    Article  PubMed  Google Scholar 

  5. LeDoux D, Astiz ME, Carpati CM, Rackow EC (2000) Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 28: 2729–2732

    Article  PubMed  CAS  Google Scholar 

  6. Spronk PE, Zandstra DF, Ince C (2004) Bench-to-bedside review: sepsis is a disease of the microcirculation. Crit Care 8: 462–468

    Article  PubMed  Google Scholar 

  7. Trzeciak S, McCoy JV, Dellinger RP, et al (2008) Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced milti-organ failure at 24 hours in patients with sepsis. Intensive Care Med 34: 2210–2217

    Article  PubMed  Google Scholar 

  8. Bateman RM, Sharpe MD, Ellis CG (2003) Bench-to-bedside review: microvascular dysfunction in sepsis-hemodynamics, oxygen transport, and nitric oxide. Crit Care 7: 359–373

    Article  PubMed  Google Scholar 

  9. Ellis CG, Bateman RM, Sharpe MD, Sibbald WJ, Gill R (2002) Effect of a maldistribution of microvascular blood flow on capillary 0(2) extraction in sepsis. Am J Physiol Heart Circ Physiol 282: H156–H164

    PubMed  CAS  Google Scholar 

  10. Ospina-Tascon G, Neves AP, Occhipinti G, et al (2010) Effects of fluids on microvascular perfusion in patients with severe sepsis. Intensive Care Med 36: 949–955

    Article  PubMed  Google Scholar 

  11. Mohammud I, Nonas SA (2010) Mechanisms, detection, and potential management of microcirculatory disturbances in sepsis. Crit Care Clin 26: 393–408

    Article  Google Scholar 

  12. Loiacono LA, Shapiro DS (2010) Detection of hypoxia at the cellular level. Crit Care Clin 26: 409–421

    Article  PubMed  CAS  Google Scholar 

  13. Marik PE, Preiser JC (2010) Toward understanding glycemie control in the ICU. Chest 137: 544–551

    Article  PubMed  CAS  Google Scholar 

  14. Tracey KJ, Fong Y, Hesse DG, et al (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330: 662–664

    Article  PubMed  CAS  Google Scholar 

  15. Dandona P, Aljada A, Mohanty P, et al (2001) Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J Clin Endocrinol Metab 86: 3257–3265

    Article  PubMed  CAS  Google Scholar 

  16. Jeschke MG, Klein D, Bolder U, Einspanier R (2004) Insulin attenuates the systemic inflammatory response inendotoxemic rats. Endocrinology 145: 4084–4093

    Article  PubMed  CAS  Google Scholar 

  17. Kline JA, Raymond RM, Leonova ED, Williams TC, Watts JA (1997) Insulin improves heart function and metabolism during non-ischemic cardiogenic shock in awake canines. Cardiovasc Res 34: 289–298

    Article  PubMed  CAS  Google Scholar 

  18. Vincent MA, Clerk LH, Rattigan S, Clark MG, Barrett E (2005) Active role for the vasculature in the delivery of insulin to skeletal muscle. Clin Exp Pharmacol Physiol 32: 302–307

    Article  PubMed  CAS  Google Scholar 

  19. Zuran I, Poredos P, Skale R, Voga G, Gabršek L, Pareflnik R (2009) Intensive insulin treatment improves forearm blood flow in critically ill patients: a randomized parallel design clinical trial. Crit Care 13: R198

    Article  PubMed  Google Scholar 

  20. Singer M (2007) Mitochondrial dysfunction in sepsis: Acute phase versus multiple organ failure. Crit Care Med 35: S441–S448

    Article  PubMed  CAS  Google Scholar 

  21. Zhang Q, Raoof M, Chen Y, et al (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464: 104–108

    Article  PubMed  CAS  Google Scholar 

  22. Huebinger RM, Gomez R, McGee D, et al (2010) Association of mitochondrial allele 4216C with increased risk for sepsis-related organ dysfunction and shock after burn injury. Shock 33: 19–23

    Article  PubMed  CAS  Google Scholar 

  23. Watts JA, Kline JA (2003) Bench to bedside: the role of mitochondrial medicine in the pathogenesis and treatment of cellular injury. Acad Emerg Med 10: 985–997

    Article  PubMed  Google Scholar 

  24. Hotchkiss RS, Karl IE (1992) Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA 267: 1503–1510

    Article  PubMed  CAS  Google Scholar 

  25. Fink MP (2002) Bench-to-bedside review: Cytopathic hypoxia. Crit Care 6: 491–499

    Article  PubMed  Google Scholar 

  26. Leverve XM (2007) Mitochondrial function and substrate availability. Crit Care Med 35: S454–S460

    Article  PubMed  CAS  Google Scholar 

  27. Horvath EM, Benko R, Gero D, Szabo C (2008) Treatment with insulin inhibits poly(ADP-ribose)polymerase activation in a rat model of endotoxemia. Life Sci 82: 205–209

    Article  PubMed  CAS  Google Scholar 

  28. Vanhorebeek I, De Vos R, Mesotten D, Wouters PJ, De Wolf-Peeters C, Van Den Berghe G (2005) Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients. Lancet 365: 53–59

    Article  PubMed  CAS  Google Scholar 

  29. Dare AJ, Phillips ARJ, Hickey ARJ, et al (2009) A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome. Free Rad Biol Med 47: 1517–1525

    Article  PubMed  CAS  Google Scholar 

  30. Levy RJ, Deutschman CS (2007) Cytochrome c oxidase dysfunction in sepsis. Crit Care Med 35: S468–S475

    Article  PubMed  CAS  Google Scholar 

  31. Alamdari N, Constantin-Teodosiu D, Murton AJ, Gardiner SM, Bennett T, Layfield R (2008) Temporal changes in the involvement of pyruvate dehydrogenase complex in muscle lactate accumulation during lipopolysaccharide infusion in rats. J Physiol 586: 1767–1775

    Article  PubMed  CAS  Google Scholar 

  32. Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H (1986) Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol 250: E634–E640

    PubMed  CAS  Google Scholar 

  33. Stacpoole PW, Wright EC, Baumgartner TG, et al (1992) A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. N Engl J Med 327: 1564–1569

    Article  PubMed  CAS  Google Scholar 

  34. Dhainaut JF, Huyghebaert MF, Monsallier JF, et al (1987) Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock. Circulation 75: 533–541

    PubMed  CAS  Google Scholar 

  35. Calvani M, Reda E, Arrigoni-Martelli E (2000) Regulation by carnitine of myocardial fatty acid and carbohydrate metabolism under normal and pathological conditions. Basis Res Cardiol 95: 75–83

    Article  CAS  Google Scholar 

  36. Ferrannini E, Buzzigoli G, Bevilacqua S, et al (1988) Interaction of carnitine with insulin-stimulated glucose metabolism in humans. Am J Physiol 255: E946–E952

    PubMed  CAS  Google Scholar 

  37. Dhainaut JF, Huyghebaert MF, Monsallier JF, et al (1987) Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock. Circulation 75: 533–541

    PubMed  CAS  Google Scholar 

  38. Levy B, Mansart A, Montemont A, et al (2007) Myocardial lactate deprivation is associated with decreased cardiovascular performance, decreased myocardial energetics, and early death in endotoxic shock. Intensive Care Med 33: 495–502

    Article  PubMed  CAS  Google Scholar 

  39. Aghajani E, Korvald C, Nordhaug D, et al (2004) E. Coli sepsis induces profound mechanoenergetic inefficiency in the porcine left ventricle. Shock 21: 103–109

    Article  Google Scholar 

  40. Eaton S, Zammit VA, Pierro A, Spitz L, Stefanutti G, Fukumoto K (2003) Myocardial carnitine palmitoyltrasferase 1 as a traget for oxidative modification in inflammation and sepsis. Biochem Soc Trans 31: 1133–1136

    Article  PubMed  CAS  Google Scholar 

  41. Lanza-Jacoby S, Holahan M, Beibel DK (1988) Changes in tissue leels of carnitine during E-coli sepsis in the rat. Circ Shock 24: 29–34

    PubMed  CAS  Google Scholar 

  42. Hulsmann WC (1993) Vulnerability of vascular endothelium in lipopolysaccharide toxicity: effect of (acyl) carnitine on endothelial stability. Mediators Inflamm 2: S21–S23

    Article  PubMed  CAS  Google Scholar 

  43. Rebouche CJ (2004) Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann NY Acad Sci 1033: 30–41

    Article  PubMed  CAS  Google Scholar 

  44. Nani G, Pittiruti M, Giovannini I, Boldrini G, Ronconi P, Castagneto M (1985) Plasma carnitine levels and urinary carnitine excretion during sepsis. J Parenter Enteral Nutr 9: 483–490

    Article  Google Scholar 

  45. Yamakawa M, Maeda J, Nakamura T, et al (1996) Distribution of endogenous and exogenous carnitine in rats with sepsis and acute liver failure. Clin Nutr 15: 133–140

    Article  PubMed  CAS  Google Scholar 

  46. Penn D, Zhang L, Bobrowski PJ, Quinn M, Liu X, McDonough KH (1998) Carnitine deprivation adversely affects cardiovascular response to bacterial endotoxin (LPS) in the anesthetized neonatal pig. Shock 10: 377–382

    Article  PubMed  CAS  Google Scholar 

  47. Broderick TL, DiDomenico D, Gamble J, et al (1995) L-carnitine improvement of cardiac function is associated with a stimulation in glucose but not fatty acid metabolism in carnitine-deficient hearts. Cardiovasc Res 30: 815–820

    PubMed  CAS  Google Scholar 

  48. Hulsmann WC, Dubelaar ML (1992) Carnitine requirement of vascular endothelial and smooth muscle cells in imminent ischemia. Mol Cell Biochem 116: 125–129

    Article  PubMed  CAS  Google Scholar 

  49. Gasparetto A, Corbucci GG, de Blasi RA, et al (1991) Influence of acetyl-1-carnitine infusion on haemodynamic parameters and survival of circulatory-shock patients. Int J Clin Pharm Res 11: 83–92

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency Medicine, Carolinas Medical Center, 1000 Blythe Blvd MEB 3006, Charlotte, NC, 28203, USA

    M. A. Puskarich & A. E. Jones

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  1. M. A. Puskarich
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  2. A. E. Jones
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Editors and Affiliations

  1. Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent (Head) (Head)

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Puskarich, M.A., Jones, A.E. (2011). Mitochondrial Function in Septic Shock. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2011. Annual Update in Intensive Care and Emergency Medicine 2011, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18081-1_32

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  • DOI: https://doi.org/10.1007/978-3-642-18081-1_32

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-18080-4

  • Online ISBN: 978-3-642-18081-1

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