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The Cell, the Mitochondrion, Oxygen and Sepsis

  • Conference paper
Yearbook of Intensive Care and Emergency Medicine

Part of the book series: Yearbook of Intensive Care and Emergency Medicine ((YEARBOOK,volume 1996))

Abstract

The characterization of sepsis by its metabolic components has supported the view that tissue hypoxia and hypoperfusion are causal factors. Despite suggestions of microcirculatory dysfunction and/or regional blood flow redistribution, the prolonged metabolic sequelae of sepsis cannot be adequately explained by prolonged tissue hypoxia. Recent evidence suggests that oxygen is available in abundance at cellular level and that cell damage associated with sepsis may be a consequence of disruption to normal bioenergetic pathways, that is, a malutilization of oxygen (O2) rather than inadequate delivery. Although contradictory to the mainstream view, studies stretching back 25 years lend credence to this alternative hypothesis. This chapter will attempt to reassess this confusing subject and provide evidence for and against hypoxic injury in sepsis.

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References

  1. Cybulsky MI, Chan MK, Movat HZ (1988) Acute inflammation and microthrombosis induced by endotoxin, interleukin-1, tumour necrosis factor alpha and prostaglandin E2 and their implication in gram-negative infection. Lab Invest 58: 365–378

    PubMed  CAS  Google Scholar 

  2. Nelson DP, Samsel RW, Wood L, Schumacker PT (1988) Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia. J Appl Physiol 64: 2410–2419

    PubMed  CAS  Google Scholar 

  3. Fink MP, Morrisey PE, Stein KL, et al (1988) Systemic and regional hemodynamic effects of cyclooxygenase and thromboxane synthetase inhibition in normal and hyperdynamic endotoxemic rabbits. Circ Shock 26: 41–57

    PubMed  CAS  Google Scholar 

  4. Jepson MM, Cox M, Bates PC, et al (1987) Regional blood flow and skeletal muscle energy status in endotoxemic rats. Am J Physiol 253:E581-E587

    Google Scholar 

  5. Drazenovic R, Samsel RW, Wylam ME, et al (1992) Regulation of perfused capillary density in canine intestinal mucosa during endotoxemia. J Appl Physiol 72: 259–265

    Article  PubMed  CAS  Google Scholar 

  6. Schaefer CF, Lerner MR, Biber B (1995) Oxygen metabolism changes and outcome in response to immediate colloid treatment in the endotoxaemic rat. Acta Anaesthesiol Scand 39: 43–49

    Article  PubMed  CAS  Google Scholar 

  7. Esbenshade AM, Newman JH, Lams PM, et al (1982) Respiratory failure after endotoxin infusion in sheep: Lung mechanics and lung fluid balance. J Appl Physiol 53: 967–976

    PubMed  CAS  Google Scholar 

  8. Weiner DE (1970) Effects of endotoxin on cerebral blood flow in the monkey. Am J Physiol 218: 160–164

    PubMed  CAS  Google Scholar 

  9. Mori E, Hasebe M, Kobayashi K, Iijima N (1987) Alterations in metabolite levels in carbohydrate and energy metabolism of rat in hemorrhagic shock and sepsis. Metabolism 36: 14–20

    Article  PubMed  CAS  Google Scholar 

  10. Rackow EC, Astiz ME, Weil MH (1987) Increases in oxygen extraction during rapidly fatal septic shock in rats. J Lab Clin Med 109: 660–664

    PubMed  CAS  Google Scholar 

  11. Boczkowski J, Vicaut E, Aubier M (1992) In vivo effects of E. coli endotoxemia on diaphragmatic microcirculation in rats. Am J Physiol 72: 2219–2224

    CAS  Google Scholar 

  12. Rosser DM, Stidwill RP, Jacobson D, Singer M (1995) Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis. J Appl Physiol 79 (In press)

    Google Scholar 

  13. Schaefer CF, Biber B, Lerner MR, Jobsis-Vander Vliet FF, Fagraeus L (1991) Rapid reduction of intestinal cytochrome a,a3 during lethal endotoxemia. J Surg Res 51: 382–391

    Article  PubMed  CAS  Google Scholar 

  14. Nelson DP, Beyer C, Samsel RW, Wood LDH, Schumacker PT (1987) Pathological supply dependence of O2 uptake during bacteremia in dogs. J Appl Physiol 63: 1487–1492

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Vincent JL, Dufaye P, Berré J, Leeman M, Degaute JP, Kahn RJ (1983) Serial lactate determinations during circulatory shock. Crit Care Med 11: 449–451

    Article  PubMed  CAS  Google Scholar 

  17. Hurtado FJ, Gutierrez AM, Silva N, et al (1992) Role of tissue hypoxia as the mechanism of lactic acidosis during E. coli endotoxemia. J Appl Physiol 72: 1895–1901

    PubMed  CAS  Google Scholar 

  18. Warren AP, James MH, Menzies DE, Widnell CC, Whitaker-Dowling PA, Pasternak CA (1986) Stress induces an increased hexose uptake in cultured cells. J Cell Physiol 128: 383–388

    Article  PubMed  CAS  Google Scholar 

  19. Widnell CC, Baldwin SA, Davies A, Martin S, Pasternak CA (1990) Cellular stress induces a redistribution of the glucose transporter. FASEB J 4: 1634–1637

    PubMed  CAS  Google Scholar 

  20. Tresarden JC, Threlfall CJ, Wilford K, Irving MH (1988) Muscle adenosine 5’ -triphosphate and creatine phosphate concentrations in relation to nutritional status and sepsis in man. Clin Sci 75: 233–242

    Google Scholar 

  21. Kilpatrick-Smith L, Erecinska M (1983) Cellular effects of endotoxin in vitro. I Effect of endotoxin on mitochondrial substrate metabolism and intracellular calcium. Circ Shock 11: 85–99

    PubMed  CAS  Google Scholar 

  22. Vary TC, Siegal 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 

  23. Vary TC (1991) Increased pyruvate dehydrogenase activity in response to sepsis. Am J Physiol 260: E669-E674

    PubMed  CAS  Google Scholar 

  24. Burns AH, Giaimo ME, Summer WR (1986) Dichloroacetic acid improves in vitro myocardial function following in vivo endotoxin administration. J Crit Care 1: 11–17

    Article  CAS  Google Scholar 

  25. Ellsworth ML, Ellis CG, Popel AS, Pittman RN (1994) Role of microvessels in oxygen supply to tissue. NIPS 9: 119–123

    Google Scholar 

  26. Boekstegers P, Weidenhofer S, Pilz G, Werdan K (1991) Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: Comparison to limited infection and cardiogenic shock. Infection 19: 317–323

    Article  PubMed  CAS  Google Scholar 

  27. Boeksteggers P, Weidenhofer S, Zell R, et al (1994) Changes in skeletal muscle PO2 after administration of anti-TNFa antibody in patients with severe sepsis: Comparison to interleukin-6 serum levels, APACHE II, and Elebute scores. Shock 1: 246–253

    Article  Google Scholar 

  28. Mizock B (1984) Septic shock: A metabolic perspective. Arch Int Med 144: 579–585

    Article  CAS  Google Scholar 

  29. Rosser D, Stidwill R, Millar CM, Singer M (1996) The effect of norepinephrine and dobutamine on bladder epithelial oxygen tension. Chest (in press)

    Google Scholar 

  30. Singer M, Millar C, Stidwill R, Unwin R (1996) Bladder epithelial oxygen tension - a new means of monitoring regional perfusion? Preliminary study in a model of exsanguination/fluid repletion. Intensive Care Med (in press)

    Google Scholar 

  31. Vallet B, Lund N, Curtis SE, Kelly D, Cain SM (1994) Gut and muscle tissue PO2 in endotoxaemic dogs. J Appl Physiol 76: 793–800

    PubMed  CAS  Google Scholar 

  32. VanderMeer TJ, Wang H, Fink MP (1995) Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock. Crit Care Med 23: 1217–1226

    Article  PubMed  CAS  Google Scholar 

  33. Hotchkiss RS, Rust RS, Dence CS, et al (1991) Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F] fluoromisonidazole. Am J Physiol 261: R965-R972

    PubMed  CAS  Google Scholar 

  34. Hunt TK, Rabkin J, Jensen JA, Jonsson K, von Smitten K, Goodson W (1987) Tissue oximetry: An interim report. World J Surg 11: 126–132

    Article  PubMed  CAS  Google Scholar 

  35. Connett RJ, Honig CR, Gayeski TEJ, Brooks GA (1990) Defining hypoxia: A systems view of VO2, glycolysis, energetics and intracellular PO2. J Appl Physiol 68: 833–842

    PubMed  CAS  Google Scholar 

  36. Jobsis-Vander Vliet FF (1985) Non invasive, near infrared monitoring of cellular oxygen sufficiency in vivo. In: Kreuzer F, Cain SM, Turek Z, Goldstick TK (eds) Oxygen transport to the tissue. VII. Plenum, New York, pp 833–841

    Google Scholar 

  37. Schaefer CF, Lerner MR, Biber B (1991) Dose-related reduction of intestinal cytochrome a,a3 induced by endotoxin in rats. Circ Shock 33: 17–25

    PubMed  CAS  Google Scholar 

  38. Schaefer CF, Biber B (1993) Effects of endotoxemia on the redox level of brain cytochrome a,a3 in rats. Circ Shock 40: 1–8

    PubMed  CAS  Google Scholar 

  39. Simonson SG, Welty-Wolf K, Huang YC (1994) Altered mitochondrial redox responses in gram-negative septic shock in primates. Circ Shock 43: 34–43

    PubMed  CAS  Google Scholar 

  40. Harris RA, Harris DL, Green DE (1968) Effect of Bordetella endotoxin upon mitochondrial respiration and energized processes. Arch Biochem Biophys 128: 219–230

    Article  PubMed  CAS  Google Scholar 

  41. Mela L, Miller LD, Diaco JF, Sugerman HJ (1970) Effect of E. coli on mitochondrial energy-linked functions. Surgery 68: 541–549

    Google Scholar 

  42. White RR, Mela L, Bacalzo LV, Olofsson K, Miller LD (1973) Hepatic ultrastructure in endotoxemia, hemorrhage and hypoxia: Emphasis on mitochondrial changes. Surgery 73: 525–534

    PubMed  CAS  Google Scholar 

  43. Takavoli H, Mela L (1982) Alterations of mitochondrial metabolism and protein concentrations in subacute septicemia. Infect Immun 38: 536–541

    Google Scholar 

  44. Jacobs DO, Maris J, Fried R (1988) In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis. Arch Surg 123: 1425–1428

    PubMed  CAS  Google Scholar 

  45. Jacobs DO, Kobayashi T, Imagire J, Grant C, Kesselly B, Wilmore DW (1991) Sepsis alters skeletal muscle energetics and membrane function. Surgery 110: 318–326

    PubMed  CAS  Google Scholar 

  46. Mori E, Hasebe M, Kobayashi K, Iijima N (1987) Alterations in metabolite levels in carbohydrate and energy metabolism of rat in hemorrhagic shock and sepsis. Metabolism 36: 14–20

    Article  PubMed  CAS  Google Scholar 

  47. Jepson MM, Cox M, Bates PC, et al (1987) Regional blood flow and skeletal muscle energy status in endotoxemic rats. Am J Physiol 252:E581-587

    PubMed  CAS  Google Scholar 

  48. Astiz M, Rackow EC, Well MH, Schumer W (1988) Early impairment of oxidative metabolism and energy production in severe sepsis. Circ Shock 26: 311–320

    PubMed  CAS  Google Scholar 

  49. Lancaster JR, Laster SM, Gooding LR (1989) Inhibition of target cell mitochondrial electron transfer by tumor necrosis factor. FEBS Letters 248: 169–174

    Article  PubMed  CAS  Google Scholar 

  50. Geng Y, Hansson GK, Holme E (1992) Interferon-γ and tumor necrosis factor synergize to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth muscle cells. Circ Res 71: 1268–1276

    PubMed  CAS  Google Scholar 

  51. Petros A, Bennett D, Vallance P (1991) Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 338: 1557–58

    Article  PubMed  CAS  Google Scholar 

  52. Drapier JC, Hibbs JB (1988) Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J Immunol 140: 2829–2838

    PubMed  CAS  Google Scholar 

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Authors
  1. D. Jacobson
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  2. M. Singer
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Editor information

Editors and Affiliations

  1. Department of Intensive Care, Erasme Hospital, Free University of Brussels, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent (Clinical Director) (Clinical Director)

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© 1996 Springer-Verlag Berlin Heidelberg

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Jacobson, D., Singer, M. (1996). The Cell, the Mitochondrion, Oxygen and Sepsis. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine. Yearbook of Intensive Care and Emergency Medicine, vol 1996. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80053-5_23

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  • DOI: https://doi.org/10.1007/978-3-642-80053-5_23

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-60552-2

  • Online ISBN: 978-3-642-80053-5

  • eBook Packages: Springer Book Archive

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