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Tissue Response to Different Hypoxic Injuries and Its Clinical Relevance

  • Adriano José Pereira
  • Eliézer Silva
Chapter

Abstract

Classical understanding about tissue hypoxia has evolved over time from a simple lack of oxygen to a complex net of effects involving hemodynamic and metabolic factors, endocrine and neural stimuli, inflammation, and complex molecular pathways. Hypoxia-inducible factor (HIF) discovery opened a new chapter in hypoxia understanding, due to its pleiotropic and ubiquitous interactions, physiologically or during diseases. Global responses to specific hypoxic insults are described in literature, but tissue-specific responses were usually studied on a restricted number of organs, or in mixed models, from which not always the impact of each hypoxic injury can be isolated. Different insults seem to elicit different effects on tissues, and tolerance may be not the same. New concepts are rapidly emerging from this field as permissive hypoxia, VO2 manipulation, obesity paradox, and adipose tissue hypoxia, and such insights should serve as driving forces for advances in mechanistic research and the search for new therapeutic targets in critical illness in the near future.

Keywords

Tissue hypoxia Cell hypoxia Hypoxia adaptation Hypoxic hypoxia Circulatory hypoxia Anemic hypoxia Cytopathic hypoxia Dysoxia Hypoxia-inducible factor (HIF) Prolyl hydroxylase domain (PHD) proteins 

References

  1. 1.
    Taylor CT, Doherty G, Fallon PG, Cummins EP. Hypoxia-dependent regulation of inflammatory pathways in immune cells. J Clin Invest. 2016;126(10):3716–24.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Gassmann M, Muckenthaler MU. Adaptation of iron requirement to hypoxic conditions at high altitude. J Appl Physiol. 2015;119(12):1432–40.CrossRefPubMedGoogle Scholar
  3. 3.
    Semenza GL. Life with oxygen. Science. 2007;318(5847):62–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Birch SB. Oxygen gas as a therapeutic agent. Br Med J. 1867;1(333):567–8.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Barcroft J. Discussion on the therapeutic uses of oxygen. Proc R Soc Med. 1920;13:59–68.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Henderson Y. False remedies for carbon monoxide asphyxia. Science. 1933;78(2027):408–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Courville CB. Asphyxia as a consequence of nitrous oxide anesthesia. Medicine. 1936;15:129.Google Scholar
  8. 8.
    Krogh A. The spectrocomparator, an apparatus designed for the determination of the percentage saturation of blood with oxygen or carbon monoxide. J Physiol. 1919;52(5):281–7.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Haldane J. The colorimetric determination of haemoglobin. J Physiol. 1901;26(6):497–504.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Swan HJ, Ganz W, Forrester J, Marcus H, Diamond G, Chonette D. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. N Engl J Med. 1970;283(9):447–51.CrossRefPubMedGoogle Scholar
  11. 11.
    Alella A, Williams FL, Bolene-Williams C, Katz LN. Interrelation between cardiac oxygen consumption and coronary blood flow. Am J Phys. 1955;183(3):570–82.Google Scholar
  12. 12.
    Maas JJ, de Wilde RB, Aarts LP, Pinsky MR, Jansen JR. Determination of vascular waterfall phenomenon by bedside measurement of mean systemic filling pressure and critical closing pressure in the intensive care unit. Anesth Analg. 2012;114(4):803–10.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Dyess DL, Christenberry DP, Peeples GL, Collins JN, Ardell JL, Roberts WS, Tacchi EJ, Powell RW. Organ blood flow redistribution in response to hypoxemia in neonatal piglets. J Investig Surg. 1998;11(6):381–92.CrossRefGoogle Scholar
  14. 14.
    Kato R, Pinsky MR. Personalizing blood pressure management in septic shock. Ann Intensive Care. 2015;5(1):41.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Leach RM, Treacher DF. ABC of oxygen. Oxygen transport—2. Tissue hypoxia. BMJ. 1998;317(7169):1370–3.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Jackson DC. Hibernating without oxygen: physiological adaptations of the painted turtle. J Physiol. 2002;543(Pt 3):731–7.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lutz PL, Prentice HM. Sensing and responding to hypoxia, molecular and physiological mechanisms. Integ Compr Biol. 2002;42:463–8.CrossRefGoogle Scholar
  18. 18.
    Hochachka PW, Buck LT, Doll CJ, Land SC. Unifying theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack. Proc Natl Acad Sci U S A. 1996;93:9493–8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Subramanian RM, Chandel N, Budinger GR, Schumacker PT. Hypoxic conformance of metabolism in primary rat hepatocytes: a model of hepatic hibernation. Hepatology. 2007;45(2):455–64.CrossRefPubMedGoogle Scholar
  20. 20.
    Li S, Hafeez A, Noorulla F, Geng X, Shao G, Ren C, Lu G, Zhao H, Ding Y, Ji X. Preconditioning in neuroprotection: from hypoxia to ischemia. Prog Neurobiol. 2017;157:79–91. pii: S0301–0082(15)30071-X.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mongardon N, Dyson A, Singer M. Is MOF an outcome parameter or a transient, adaptive state in critical illness? Curr Opin Crit Care. 2009;15(5):431–6.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wang GL, Semenza GL. General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci U S A. 1993;90(9):4304–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399–408.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Schönenberger MJ, Kovacs WJ. Hypoxia signaling pathways: modulators of oxygen-related organelles. Front Cell Dev Biol. 2015;3:42.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Cain SM. Appearance of excess lactate in anesthetized dogs during anemic and hypoxic hypoxia. Am J Phys. 1965;209(3):604–10.Google Scholar
  26. 26.
    Cain SM. Oxygen delivery and uptake in dogs during anemic and hypoxic hypoxia. J Appl Physiol. 1977;42(2):228–34.CrossRefPubMedGoogle Scholar
  27. 27.
    Schwartz S, Frantz RA, Shoemaker WC. Sequential hemodynamic and oxygen transport responses in hypovolemia, anemia, and hypoxia. Am J Phys. 1981;241(6):H864–71.Google Scholar
  28. 28.
    Resnik WH. Observations on the effect of anoxemia on the heart. I. Auriculo-ventricular conduction. J Clin Invest. 1925;2(1):93–115.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Spitzer JJ, Spitzer JA. Myocardial metabolism in dogs during hemorrhagic shock. Am J Phys. 1972;222(1):101–5.Google Scholar
  30. 30.
    Belkin DA. Anaerobic brain function: effects of stagnant and anoxic anoxia on persistence of breathing in reptiles. Science. 1968;162(3857):1017–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Cain SM, Adams RP. O2 transport during two forms of stagnant hypoxia following acid and base infusions. J Appl Physiol Respir Environ Exerc Physiol. 1983;54(6):1518–24.PubMedGoogle Scholar
  32. 32.
    Vallet B, Teboul JL, Cain S, Curtis S. Venoarterial CO(2) difference during regional ischemic or hypoxic hypoxia. J Appl Physiol (1985). 2000;89(4):1317–21.CrossRefGoogle Scholar
  33. 33.
    Zhang H, Spapen H, Vincent JL. Effects of dobutamine and norepinephrine on oxygen availability in tamponade-induced stagnant hypoxia: a prospective, randomized, controlled study. Crit Care Med. 1994;22(2):299–305.CrossRefPubMedGoogle Scholar
  34. 34.
    Brooks GA. Lactate shuttles in nature. Biochem Soc Trans. 2002;30(2):258–64.CrossRefPubMedGoogle Scholar
  35. 35.
    De Backer D, Creteur J, Zhang H, Norrenberg M, Vincent JL. Lactate production by the lungs in acute lung injury. Am J Respir Crit Care Med. 1997;156(4 Pt 1):1099–104.CrossRefPubMedGoogle Scholar
  36. 36.
    Fink M. Cytopathic hypoxia in sepsis. Acta Anaesthesiol Scand Suppl. 1997;110:87–95.CrossRefPubMedGoogle Scholar
  37. 37.
    Fink MP. Bench-to-bedside review: cytopathic hypoxia. Crit Care. 2002;6(6):491–9. Epub 2002 Sep 12CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 360(9328):219–23.CrossRefGoogle Scholar
  39. 39.
    Ince C. The microcirculation is the motor of sepsis. Crit Care. 2005;9(Suppl 4):S13–9. Review.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hotchkiss RS, Rust RS, Dence CS, Wasserman TH, Song SK, Hwang DR, et al. Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole. Am J Phys. 1991;261(4 Pt 2):R965–72.Google Scholar
  41. 41.
    Jeger V, Djafarzadeh S, Jakob SM, Takala J. Mitochondrial function in sepsis. Eur J Clin Investig. 2013;43(5):532–42.  https://doi.org/10.1111/eci.12069. Epub 2013 Mar 15.CrossRefGoogle Scholar
  42. 42.
    Gutierrez G. Work of breathing, not dysoxia, as the cause of low central venous blood O2 saturation in sepsis. Crit Care. 2016;20:291.  https://doi.org/10.1186/s13054-016-1476-1.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011;364(7):656–65.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Schumacker PT. Hypoxia-inducible factor-1 (HIF-1). Crit Care Med. 2005;33(12 Suppl):S423–5.CrossRefPubMedGoogle Scholar
  45. 45.
    Pickkers P, de Keizer N, Dusseljee J, Weerheijm D, van der Hoeven JG, Peek N. Body mass index is associated with hospital mortality in critically ill patients: an observational cohort study. Crit Care Med. 2013;41(8):1878–83.CrossRefPubMedGoogle Scholar
  46. 46.
    Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev. 2013;93:1–21.CrossRefPubMedGoogle Scholar
  47. 47.
    Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes. 2009;33:54–66.CrossRefGoogle Scholar
  48. 48.
    Martin DS, Khosravi M, Grocott MP, Mythen MG. Concepts in hypoxia reborn. Crit Care. 2010;14(4):315.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Panwar R, Hardie M, Bellomo R, Barrot L, Eastwood GM, Young PJ, Capellier G, Harrigan PWJ, Bailey M. Conservative versus liberal oxygenation targets for mechanically ventilated patients. A pilot multicenter randomized controlled trial. Am J Respir Crit Care Med. 2016;193(1):43.CrossRefPubMedGoogle Scholar
  50. 50.
    Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, Morelli A, Antonelli M, Singer M. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316(15):1583–9.  https://doi.org/10.1001/jama.2016.11993.CrossRefPubMedGoogle Scholar
  51. 51.
    Szabo C. Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov. 2007;6(11):917–35.CrossRefPubMedGoogle Scholar
  52. 52.
    Ackland GL, Yao ST, Rudiger A, Dyson A, Stidwill R, Poputnikov D, et al. Cardioprotection, attenuated systemic inflammation, and survival benefit of beta1-adrenoceptor blockade in severe sepsis in rats. Crit Care Med. 2010;38(2):388–94.CrossRefPubMedGoogle Scholar
  53. 53.
    Orbegozo Cortés D, Su F, Santacruz C, Hosokawa K, Donadello K, Creteur J, De Backer D, Vincent JL. Ischemic conditioning protects the microcirculation, preserves organ function, and prolongs survival in sepsis. Shock. 2016;45(4):419–27.CrossRefPubMedGoogle Scholar
  54. 54.
    Formenti F, Constantin-Teodosiu D, Emmanuel Y, Cheeseman J, Dorrington KL, Edwards LM, Humphreys SM, Lappin TR, McMullin MF, McNamara CJ, Mills W, Murphy JA, O’Connor DF, Percy MJ, Ratcliffe PJ, Smith TG, Treacy M, Frayn KN, Greenhaff PL, Karpe F, Clarke K, Robbins PA. Regulation of human metabolism by hypoxia-inducible factor. Proc Natl Acad Sci U S A. 2010;107(28):12722–7. Epub 2010 Jun 28.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Hospital Israelita Albert EinsteinSao PauloBrazil

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