Pathophysiology of VO2/DO2 in Sepsis

  • B. Vallet
Part of the Update in Intensive Care and Emergency Medicine book series (UICM, volume 28)


The high molar demand for oxygen (02) compared to other metabolic substrates implies that tissues deplete blood of 02 much sooner than of these other substrates. Under normal resting conditions, tissue 02 demand rather than tissue 02 supply (DO2) determines the rate of 02 uptake (VO2). When blood carries less than the normal amount of 02 or when blood flow is reduced, DO2 is reduced and compensatory adjustments occur in an attempt to satisfy the 02 requirements of peripheral tissues. As DO2 is gradually reduced, 02 consumption (VO2) is maintained by increases in the 02 extraction ratio (ER02 = VO2/DO2), until a critical point at which VO2 falls with further declines in DO2. At this critical point, tissues shift toward a chemically reduced state with elaboration of reduced substrate forms such as lactate. It has been proposed that increased ER02 is a consequence of regulation of the circulation and the result of the simultaneous activation of both central and local factors. Central factor induces a regional redistribution of blood flow among tissues via sympathetic vasoconstrictor tone while local factor or autoregulation induces an increase in the density of perfused capillaries within tissues via metabolic vasodilator tone. Local autoregulatory processes include local release and action of vasodilating substances. An inability to regulate blood flow distribution, between and within tissues, could result in hyperperfusion of some tissue beds at the expense of other hypoperfused areas resulting in 02 extraction defect as seen in sepsis.


Extraction Ratio Blood Flow Distribution Hypoxic Hypoxia Vasoconstrictor Tone Supply Dependence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Schlichtig R, Kramer DJ, Pinsky MR (1991) Flow redistribution during progressive hemorrhage is a determinant of critical O2 delivery. J Appl Physiol 70:169–178.PubMedGoogle Scholar
  2. Schlichtig R (1993) O2 uptake, critical O2 delivery, and tissue wellness. In: Pinsky MR, Dhainaut JF (eds) Pathophysiologic foundations of critical care. Williams and Wilkins, Baltimore, pp 119–139.Google Scholar
  3. Nelson DP, King CE, Dodd SL, Schumacker PT, Cain SM (1987) Systemic and intestinal limits of O2 extraction in the dog. J Appi Physiol 63:387–394.Google Scholar
  4. Nelson DP, Samsel RW, Wood LDH, Schumacker PT (1988) Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia. J Appl Physiol 64:2410–2419.PubMedGoogle Scholar
  5. Ward ME, Chang H, Erice F, Hussain SNA (1994) Systemic and diaphragmatic oxygen delivery-consumption relationships during hemorrhage. J Appi Physiol 77:653–659.Google Scholar
  6. Samsel RW, Nelson DP, Sanders WM, Wood LDH, Schumacker PT (1988) Effect of endotoxin on systemic and skeletal muscle O2 extraction. J Appi Physiol 65:1377–1382.Google Scholar
  7. Bredle DL, Samsel RW, Schumacker PT, Cain SM (1989) Critical O2 delivery to skeletal muscle at high and low PO2 in endotoxemic dogs. J Appi Physiol 66:2553–2558.Google Scholar
  8. Cain SM (1978) Effects of time and vasoconstrictor tone on O2 extraction during hypoxic hypoxia. J Appi Physiol 45:219–278.Google Scholar
  9. Pinsky MR (1995) Regional blood flow distribution. In: Pinsky MR, Dhainaut JF, Artigas A (eds) The splanchnic circulation: no longer a silent partner. Springer-Verlag. Berlin, pp 1–13.Google Scholar
  10. Granger HJ, Goodman AH, Cook Billy H (1975) Metabolic models of microcirculatory regulation. Federation Proc 34:2O25–2030.Google Scholar
  11. Samsel RW, Schumacker PT (1992) Pathologic supply dependence of oxygen utilization. In: Principles of critical care medicine. Williams and Wilkins, Baltimore, pp 667–678.Google Scholar
  12. Maginiss LA, Connolly H, Samsel RW, Schumacker PT (1994) Adrenergic vasoconstriction augments tissue O2 extraction during reductions in O2 delivery. J Appi Physiol 76:1454–1461.Google Scholar
  13. Samsel RW, Schumacker PT (1994) Systemic hemorrhage augments local O2 extraction. J Appi Physiol 77:2291–2298.Google Scholar
  14. Cain SM, Chapter CK (1981) Effects of norepinephrine and alpha-block on O2 uptake and blood flow in dog hindlimb. J Appi Physiol 51:1245–1250.Google Scholar
  15. Skinner NS, Costin JC (1968) Tissue metabolites and regulation of local blood flow. Fed Proc 27:1426–1429.PubMedGoogle Scholar
  16. Pohl U (1990) Endothelial cells as a part of a vascular oxygen-sensing system: hypoxia-induced release of autacoids. Experientia 46:1175–1179.PubMedCrossRefGoogle Scholar
  17. Vanhoutte PM (1989) Endothelium and control of vascular function. State of the art lecture. Hypertension 13:658–667.Google Scholar
  18. Pohl U, Busse R (1989) Hypoxia stimulates release of endothelium-derived relaxant factor. Am J Physiol 956:H1595–1600.Google Scholar
  19. Michiels C, Arnould T, Dieu M, Remacle J (1993) Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia. Am J Physiol 264: C866–C874.PubMedGoogle Scholar
  20. Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT (1989) Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science Wash DC 245:177–180.CrossRefGoogle Scholar
  21. Daut J, Maier-Rudolph W, Von Beckerath N, Mehrke G, Günther K, Goedel-Meinen L (1990) Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. Science Wash DC 247:1341–1344.CrossRefGoogle Scholar
  22. Vallet B, Curtis SE, Guery B, Mangalaboyi J, Menager P, Cain SM, Chopin C, Dupuis BA (1995) ATP-sensitive K + channel blockade impairs oxygen extraction during progressive ischemia in pig hindlimb. J Appi Physiol 79:2035–2042.Google Scholar
  23. Curtis SE, Vallet B, Winn MJ, Caufield JB, Cain SM (1995) Ablation of the vascular endothelium causes an oxygen extraction defect in canine skeletal muscle. J Appi Physiol 79: 1352–1360.Google Scholar
  24. Nelson DP, Bever C, Samsel RW, Wood L, Schumacker PT (1987) Pathological supply depen¬dence of O2 uptake during bacteremia in dogs. J Appl Physiol 63:1487–1492.PubMedGoogle Scholar
  25. Van Lambalgen AA, Bronsveld W, Van den Bos GC, Thijs KG (1984) Distribution of cardiac output, oxygen consumption and lactate production in canine endotoxic shock. Cardiovasc Res 18:195–201.PubMedCrossRefGoogle Scholar
  26. Breslow MJ, Miller CF, Parker SD, Walman AT, Traystman RJ (1987) Effect of vasopressors on organ blood flow during endotoxin shock in pigs. Am J Physiol 252: H291–300.PubMedGoogle Scholar
  27. Carrol G, Synder J (1982) Hyperdynamic severe intravascular sepsis depends on fluid ad-ministration in cyonomolgus monkey. Am J Physiol 243:R131–141.Google Scholar
  28. Garrisson RN, Ratcliffe DJ, Fry DE (1980) Hepatocellular function and nutrient blood flow in experimental peritonitis. Surgery 92:713–719.Google Scholar
  29. Umans JG, Wylam ME, Samsel RW, Edwards J, Schumacker PT (1993) Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta. Am Rev Repir Dis 148:1638–1645.CrossRefGoogle Scholar
  30. Wakabayashi I, Hatake K, Kakishita E, Nagai K (1987) Diminution of contractile response of the aorta from endotoxin-injected rats. Eur J Pharmacol 141:117–122.PubMedCrossRefGoogle Scholar
  31. Mc Kenna TM (1988) Enhanced vascular effects of cyclic GMP in septic rat aorta. Am J Physiol 23:R436–R442.Google Scholar
  32. Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stockt JC (1990) Loss of vascu¬lar responsiveness induced by endotoxin involves L-arginine pathway. Am J Physiol 259: H1038–H1043.PubMedGoogle Scholar
  33. Parker JL, Keller RS, DeFily DV, Laughlin MH, Novotny MJ, Adams HR (1991) Coronary vas-cular smooth muscle function in E. coli endotoxemia in dogs. Am J Physiol 260: H832–H842.PubMedGoogle Scholar
  34. Schumacker PT, Kazaglis J, Connolly HV, Samsel RW, O’Connor MF, Umans JG (1995) Systemic and gut oxygen extraction during endotoxemia: role of nitric oxide synthesis. Am J Respir Crit Care Med 151:107–115.PubMedGoogle Scholar
  35. Vallet B, Curtis SE, Winn MJ, King CE, Chapler CK, Cain SM (1994) Hypoxic vasodilation does not require nitric oxide (EDRF/NO) synthesis. J Appl Physiol 76:1256–1261.PubMedCrossRefGoogle Scholar
  36. Peterson DA, Peteron DC, Archer S, Weir EK (1992) The nonspecificity of specific nitric oxide synthase inhibitors. Biochem Biophys Res Commun 187:797–801.PubMedCrossRefGoogle Scholar
  37. Winn MJ, Asante NK, Ku DD (1993) Vasomotor responses of canine arterial rings to NG-monomethyl-L-arginine and Nw-nitro L-arginine methyl ester. J Pharmacol Exp Ther 264: 265–270.PubMedGoogle Scholar
  38. Winn MJ, Vallet B, Asante NK, Curtis SE, Cain SM (1993) Effects of NG-substituted arginines on coronary vascular function after endotoxin. J Appl Physiol 75:424–431.PubMedGoogle Scholar
  39. Wright CE, Rees DD, Moneada S (1992) Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc Res 26:48–57.PubMedCrossRefGoogle Scholar
  40. Cobb JP, Natanson C, Quezado ZMN, Hoffman WD, Koev CA, Banks S, Correa R, Levi R, Elin RJ, Hosseini JM, Danner RL (1995) Differential hemodynamic effects of L-NMMA in endotoxemic and normal dogs. Am J Physiol 268: H1634–H1642.PubMedGoogle Scholar
  41. Smith RE, Palmer RMJ, Moneada S (1991) Coronary vasodilation induced by endotoxin in the rabbit isolated perfused heart is nitric oxide-dependent and inhibited by dexametha-sone. Br J Pharmacol 140:5–6.Google Scholar
  42. Lübbe AS, Garrison RN, Cryer HM, Alsip NL, Harris PD (1992) EDRF as a possible mediator of sepsis-induced arteriolar dilation in skeletal muscle. Am J Physiol 262: H880–H887.PubMedGoogle Scholar
  43. Schneider F, Schott C, Stoclet JC, Julou-Schaeffer G (1992) L-arginine induces relaxation of small mesenteric arteries from endotoxin-treated rats. Eur J Pharmacol 211:269–272.PubMedCrossRefGoogle Scholar
  44. Lam C, Tyml K, Martin C, Sibbald W (1994) Microvascular perfusion is impaired in a rat model of normotensive sepsis. J Clin Invest 94:2077–2083.PubMedCrossRefGoogle Scholar
  45. Landry DW, Oliver JA (1992) The ATP-sensitive K+ channel mediates hypotension in endo-toxemia and hypoxic lactic acidosis in dog. J Clin Invest 89:2071–2074.PubMedCrossRefGoogle Scholar
  46. Bredle DL, Cain SM (1991) Systemic and muscle oxygen uptake/delivery after dopexamine infusion in endotoxic dogs. Crit Care Med 19:198–204.PubMedCrossRefGoogle Scholar
  47. Vallet B, Lund N, Curtis SE, Kelly DR, Cain SM (1994) Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation.! Appi Physiol 76:793–800.Google Scholar
  48. Thorborg P, Malmqvist LA, Lund N (1988) Surface oxygen pressure distributions in rabbit skeletal muscle: dependence on arterial PO2. Microcirc Endothel Lymphatics 4:169–192.Google Scholar
  49. Gutierrez G, Lund N, Palizas F (1991) Rabbit skeletal muscle PO2 during hypodynamic sep-sis. Chest 99:224–229.PubMedCrossRefGoogle Scholar
  50. Curtis SE, Cain SM (1992) Regional and systemic oxygen delivery/uptake relations and lac-tate flux in hyperdynamic, endotoxin-treated dogs. Am Rev Respir Dis 145:348–354.PubMedGoogle Scholar
  51. Dodd SL, King CE, Cain SM (1987) Responses of innervated and denervated gut to whole-body hypoxia. J Appi Physiol 62:651–657.Google Scholar
  52. Curtis SE, Cain SM (1992b) Systemic and regional O2 delivery and uptake in bled dogs given hypertonic saline, whole blood, or dextran. Am J Physiol 262: H778–H786.PubMedGoogle Scholar
  53. Montgomery A, Hartmann M, Jonsson K, Haglund UH (1989) Intramucosal pH measure¬ment with tonometer for detecting gastrointestinal ischemia in porcine hemorrhagic shock. Circ Shock 29:319–327.PubMedGoogle Scholar
  54. Drazenovic R, Samsel RW, Wylam ME, Doerschuk CM, Schumacker PT (1992) Regulation of perfused capillary density in canine intestinal mucosa during endotoxemia. J Appi Physiol 72:259–265.CrossRefGoogle Scholar
  55. Whithworth PW, Cryer HM, Garrison RN, Baumgarten TE, Harris PD (1989) Hypoperfusion of the intestinal microcirculation without decreased cardiac output during live Escherichia coli sepsis in rats. Circ Shock 27:111–122.Google Scholar
  56. Schumacker PT, Cain SM (1987) The concept of a critical oxygen delivery. Intensive Care Med 13:223–229.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • B. Vallet

There are no affiliations available

Personalised recommendations