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Oxygénation tissulaire J. Duranteau Université Paris-Sud Hôpital de Bicêtre

Oxygénation tissulaire J. Duranteau Université Paris-Sud Hôpital de Bicêtre. Convection VO 2 = IC. (CaO 2 - CvO 2 ).10. Diffusion VO 2 = KO 2 (PvO 2 - PmitO 2 ). O 2. ATP. Fonction mitochondriale. Convection. Index cardiaque Hémoglobine Microcirculation. EO2 critique.

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Oxygénation tissulaire J. Duranteau Université Paris-Sud Hôpital de Bicêtre

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  1. Oxygénation tissulaire J. Duranteau Université Paris-Sud Hôpital de Bicêtre

  2. Convection VO2 = IC. (CaO2 - CvO2).10 Diffusion • VO2 = KO2 (PvO2 - PmitO2) O2 ATP Fonction mitochondriale

  3. Convection • Index cardiaque • Hémoglobine • Microcirculation

  4. EO2 critique Lactate Consommation d’oxygène(mL/min/m2) 200 150 100 50 0 0 100 200 300 400 500 600 700 Transport en oxygène (mL/min/m2)

  5. Oxygen uptake(mL/min/m2) 300 0 0 200 400 600 800 1000 Oxygen delivery(mL/min/m2)

  6.  PCO2  H+  Temp  2,3-DPG Saturation d’oxygène(%) 100 50 0 0 20 40 60 80 100 PO2 (mmHg)

  7. Convection • Index cardiaque • Hémoglobine • Microcirculation

  8. Effet Fahraeus-Lindqvist Endothélium

  9. Hte micro/Hte macro 1,0 0,8 0,6 Artériel veineux 60 50 40 30 20 10 10 20 30 40 50 60 70 Diamètre du vaisseau m Lipowsky HH, Microvasc Res 19:297, 1980

  10. Van Der Linden P et al., Anesthesiology. 99:97-104, 2003.

  11. Leung JM et al., Anesthesiology. 93:1004-1010, 2000. • 55 volontaires sains au repos • Cathéters artériels radial et pulmonaire • Hémodilution normovolémique : Hb = 5,2 ± 0,5 g/dL (1h) • Détection ischémies myocardiques • 3 sujets : sous décalage ST transitoire et réversible sans Symptomatologie et sans conséquences péjoratives • Modifications apparues Hb 5-7 g/dL

  12. MAIS • Réanimation = malades avec ATCD cardio-vasculaires • Hypovolémie : baisse de viscosité et bas débits • Sepsis : altération microcirculatoire

  13. O2 extraction ratio 1.0 0.8 0.6 0.4 0.2 0.0 T T T T T With endothelial cells T T T T T T T T T T Without endothelial cells T T T 0 5 10 15 20 O2 delivery (mL/kg/min) Curtis SE et al. J Appl Physiol 79: 1352-1360. 1995.

  14. Endothelium

  15. RBC flux villus capillary (mm/s) RBC flux villus tip (mm/s) 500 300 400 200 300 200 100 100 0 0 0 60 min 0 60 min Low ETX (1.5 mg/kg) High ETX (1.5 mg/kg) Control Hemorrhage

  16. ETX + NE Control ETX + NE + Arg ETX RBC flux villus tip (mm/s) 500 400 300 200 100 0 0 60 120 min

  17. Convection VO2 = IC. (CaO2 - CvO2).10 Diffusion • VO2 = KO2 (PvO2 - PmitO2) O2 ATP Fonction mitochondriale

  18. PO2 extracellulaire ∆ PO2 O2 flux PO2 mitochondriale

  19. Convection VO2 = IC. (CaO2 - CvO2).10 Diffusion • VO2 = KO2 (PvO2 - PmitO2) O2 ATP Fonction mitochondriale

  20.  EPO  iNOS  HIF1  O2  Besoins métaboliques  GLUT-1 ATP VEGF  glycolyse

  21. 4 Normoxia Hypoxia or normoxia Normoxia 120 torr 22 or 120 torr 120 torr 3 Oxygen uptake (µmol/hr/million cells) 2 Normoxia Hypoxia 1 0 0 10 20 30 40 50 60 Time (hrs) P.T. Schumacker et al. Am.J. Physiol.L395-L402, 1993.

  22. Hypoxia 20 torr recovery 120 110 100 90 80 70 Total motion (% of control values) 60 50 40 30 20 10 0 0 60 120 180 240 300 360 420 Times (min) J. Duranteau et al. J. Biol. Chem. 273:11619-11624. 1998.

  23. ATP ADP AMP 20 15 Adenine nucleotide concentrations (nmoles/million cells) 10 5 0 0 20 40 60 80 100 Oxygen tension (torr) GRS Budinger et al.Am. J. Physiol. 270: L44-L53, 1996.

  24. Oxygen (µM) Succ ADP 350 µM 200 100 0 Mt NO 0.4 1.0 2.0 3.0 µM 0 5 10 15 Time (min) Takehara et al. Arch. Biochem. Biophys.323, 27-32, 1995.

  25. Oxygen (µM) Succ ADP 600 µM 200 100 0 Mt NO (0.8 µM) NO NO NO 0 5 10 15 Time (min) Takehara et al. Arch. Biochem. Biophys.323, 27-32, 1995.

  26. O2 consumption (ng.atom.min-1.mg-1) 1.8 1.4 1 0.6 0.2 0 Control LPS King C et al. Crit Care Med 1999; 27:2518-2524.

  27. µg MTT-FZ / mg DNA 100 80 60 40 20 0 Control LPS LPS + AGuanidine Unno N. Gastroenterology 1997; 113:1246-1257.

  28. Sham (n=5) Sepsis (n=5) H0 0.13 ± 0.01 0.09 ± 0.01 0.12 ± 0.01 H4 0.12 ± 0.01 0.07 ± 0.01 0.12 ± 0.01 H0 0.14 ± 0.01 0.12 ± 0.01 0.13 ± 0.01 H4 0.11 ± 0.01 0.11 ± 0.01 0.12 ± 0.01 VO2-PM VO2-Succi VO2-Asc-TMPD Mitochondrial oxygen consumption In permeabilized muscle fibers (µmol O2/h/mg) L ’Her E and Sebert P. AJRCCM 164. 1444-1447, 2001.

  29. % cells with depolarized mitochondria (% ∆m) 25 20 15 10 5 0 Control <72 h 7-10 d discharged 30 25 20 15 10 5 0 Adrie C et al. AJRCCM 2001; 164:389-395. Survivors Non-survivors

  30. Lésions microscopiques et altérations de la respiration mitochondriale Crouser et al. Crit Care Med 2002; 30: 276-284

  31. Lésions microscopiques et altérations de la respiration mitochondriale Crouser et al. Crit Care Med 2002; 30: 276-284

  32. D. Brealy et al. The lancet 360, 20, 2002.

  33. D. Brealy et al. The lancet 360,20,2002.

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