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Changes in Cerebral Blood Flow After Endotoxin in Humans and Sheep

  • V. Pollard
  • B. Conroy
  • D. S. Prough
  • D. J. Deyo
  • L. Traber
  • D. Traber
Conference paper

Summary

Neurologic dysfunction is common in early sepsis. To better understand cerebral autoregulatory responses during sepsis, we studied cerebral hemodynamics, cerebral oxygen delivery (CDO2), and the cerebral metabolic rate for oxygen (CMRO2) in volunteers and in unanesthetized sheep during experimental endotoxemia. In ten healthy volunteers, we used a Kety-Schmidt technique to measure cerebral blood flow (CBF) at baseline and at hourly intervals for 5 h after a bolus of Escherichia coli endotoxin (4ng/kg). We also measured CMRO2, CDO2, and cerebral vascular resistance (CVR) at these time points. Volunteers developed marked systemic and hemodynamic responses after endotoxin, including an elevated body temperature, cardiac index (CI), and heart rate (HR), and a decreased mean arterial pressure (MAP) and systemic vascular resistance index (SVRI). CBF, CDO2, CMRO2, and CVR were un-changed throughout the 5-h study period. In a separate study, we measured CBF (using radiolabeled or colored microspheres), and CMRO2, CDO2, CVR, and cerebral perfusion pressure (CPP) at baseline and at 1.5, 4, and 24 h in 18 sheep during continuous E. coli endotoxin infusion (10ng/kg per hour). Eight sheep became hyperdynamic with an increased body temperature, CI, and HR, and a decreased SVRI. In the hyperdynamic sheep, CBF, CDO2, CMRO2, and CPP were elevated and CVR was decreased after 4 h of continuous endotoxin. Ten sheep did not become hyperdynamic although body temperature, white cell count, and pulmonary artery pressure had significantly increased. CBF, CDO2, CMRO2, CPP, and CVR were un-changed in these sheep.

We conclude that cerebral hemodynamics and oxygenation variables are un-changed after a bolus of endotoxin in volunteers although marked systemic responses are apparent. However, CBF, CMRO2, CDO2, and CPP are elevated and CVR is reduced in hyperdynamic sheep but unchanged in nonhyperdynamic sheep after 4 h of continuous endotoxin infusion. The responses to endotoxin may be species- or dose-dependent.

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References

  1. 1.
    Sprung CL, Peduzzi PN, Shatney SN, Schein RMH, Wilson MF, Sheagren JN, Hinshaw LB, The Veterans Administration Systemic Sepsis Cooperative Study Group (1990) Impact of encephalopathy on mortality in the sepsis syndrome. Crit Care Med 18:801–806PubMedCrossRefGoogle Scholar
  2. 2.
    Barriere SL, Lowry SF (1995) An overview of mortality risk prediction in sepsis. Crit Care Med 23:376–393PubMedCrossRefGoogle Scholar
  3. 3.
    Pine RW, Wertz MJ, Lennard EP, Dellinger CJ, Carrico CJ, Minshew BH (1983) Determinants of organ malfunction or death in patients with intraabdominal sepsis: a discriminate analysis. Arch Surg 118:242–249PubMedCrossRefGoogle Scholar
  4. 4.
    Young GB, Bolton CF, Austin TW, Archibald YM, Gonder J, Wells GA (1990) The encephalopathy associated with septic illness. Clin Invest Med 13:297–304PubMedGoogle Scholar
  5. 5.
    Jackson AC, Gilbert JJ, Young GB, Bolton CF (1985) The encephalopathy of sepsis. Can J Neurol Sci 12:303–307PubMedGoogle Scholar
  6. 6.
    Bowton DL, Bertels NH, Prough DS, Stump DA (1989) Cerebral blood flow is reduced in patients with sepsis syndrome. Crit Care Med 17:399–403PubMedCrossRefGoogle Scholar
  7. 7.
    Maekawa T, Yukimasa F, Daikai S, Yokata K, Soejima Y, Ishikawa T, Miyauchi Y, Takeshita H (1991) Cerebral circulation and metabolism in patients with septic encephalopathy. Am J Emerg Med 9:139–143PubMedCrossRefGoogle Scholar
  8. 8.
    Martich GD, Parker MM, Cunnion RE, Sufferedini AF (1992) Effects of ibuprofen and pentoxifylline on the cardiovascular response of normal humans to endotoxin. J Appl Physiol 73:925–931PubMedGoogle Scholar
  9. 9.
    Sufferedini AF, Fromm RE, Parker MM, Brenner M, Kovacs JA, Wesley RA, Parillo JE (1989) The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med 321:280–287CrossRefGoogle Scholar
  10. 10.
    Revhaug A, Michie HR, Manson JM, Watters JM, Dinarello CA, Wollf SM, Wilmore DW (1988) Inhibition of cyclo-oxygenase attenuates the metabolic response to endotoxin in humans. Arch Surg 123:162–170PubMedCrossRefGoogle Scholar
  11. 11.
    Cannon JC, Tompkins RG, Gelfand JA, Michie HR, Stanford GG, van der Meer JWM, Endres S, Lonnemann G, Corsetti J, Chernow B, Wilmore DW, Wolff SM, Burke JF, Dinarello CA (1990) Circulation interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis 161:79–84PubMedCrossRefGoogle Scholar
  12. 12.
    Spinas GA, Bloesch D, Kaufmann MT, Keller U, Dayer JM (1990) Induction of plasma inhibitors of interleukin 1 and TNF-oc activity by endotoxin administration to normal volunteers. Am J Physiol (Regulatory Integrative Comp Physiol 28) 259:R993–R997PubMedGoogle Scholar
  13. 13.
    Pollmacher T, Schreiber W, Gudewill S, Vedder H, Fassbender K, Wiedemann K, Trachsel L, Galanos C, Holsboer F (1993) Influence of endotoxin on nocturnal sleep in humans. Am J Physiol (Regulatory Integrative Comp Physiol 28) 264:R1077–R1083PubMedGoogle Scholar
  14. 14.
    Kety SS, Schmidt CF (1945) The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am J Physiol 143:53–66Google Scholar
  15. 15.
    Traber DL, Traber LD (1989) Sheep as a cardiopulmonary model. Prog Clin Biol Res 299:253–263PubMedGoogle Scholar
  16. 16.
    Sugi K, Newald J, Traber DL, Maguire JP, Herndon DN, Schlag G, Traber DL (1991) Cardiac dysfunction after acute endotoxin administration in conscious sheep. Am J Physiol 260:H1474–H1481PubMedGoogle Scholar
  17. 17.
    Traber DL, Flynn JT, Herndon DN, Redl H, Schlag G, Traber LD (1989) Comparison of the cardiopulmonary responses to single bolus and continuous infusion of endotoxin in an ovine model. Circ Shock 27:123–138PubMedGoogle Scholar
  18. 18.
    Booke M, Armstrong C, Hinder F, Traber LD, Traber DL (1994) Anesthesia in ovine sepsis: fentanyl propofol in contrast to propofol alone worsens hemodynamics and myocardial performance. Anesthesiology 81:A458 (abstr)CrossRefGoogle Scholar
  19. 19.
    Beach T, Milien E, Grenvik A (1973) Hemodynamic response to discontinuance of mechanical ventilation. Crit Care Med 1:85–90PubMedCrossRefGoogle Scholar
  20. 20.
    Talke P, Dunn A, Lawlis L, Sziebert L, White A, Herndon D, Flynn JT, Traber DL (1985) A model of ovine endotoxemia characterized by an increased cardiac output. Circ Shock 17:103–108PubMedGoogle Scholar
  21. 21.
    Demling RH, Lalonde CC, Jin L-JJ, Albs J, Fiori N (1986) The pulmonary and systemic response to recurrent endotoxemia in the adult sheep. Surgery 100:876–883PubMedGoogle Scholar
  22. 22.
    Centers for Disease Control (1990) Increase in national hospital discharge survey rates for septicemia — United States 1979–87. MMWR Morb Mortal Wkly Rep 39:31–34Google Scholar
  23. 23.
    Traber DL, Traber LD, Redl H, Schlag G (1993) Models of endotoxemia in sheep. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis and organ failure. Springer Berlin Heidelberg New York, pp 1031–1047CrossRefGoogle Scholar
  24. 24.
    Kreimeier U, Ruiz-Morales M, Messmer K (1993) Comparison of the effects of volume resuscitation with dextran 60 vs. Ringers lactate on central hemodynamics, regional blood flow, pulmonary function and blood composition during hyperdynamic endotoxemia. Circ Shock 39:89–99PubMedGoogle Scholar
  25. 25.
    Hariri RJ, Ghajar JBG, Bahramian K, Sharif S, Barie PS (1993) Alterations in intracranial pressure and cerebral blood volume in endotoxemia. Surg Gynecol Obstet 176:155–166PubMedGoogle Scholar
  26. 26.
    Miller CF, Breslow MJ, Shapiro RM, Traystman RJ (1987) Role of hypotension in decreasing cerebral blood flow in porcine endotoxemia. Am J Physiol 253:H956–H964PubMedGoogle Scholar
  27. 27.
    Pollard V, DeMelo E, Prough DS, Traber LD, Traber DL (1993) Cerebral metabolic rate and cerebral blood flow are uncoupled during endotoxemia in sheep. Anesthesiology 79:A784 (abstr)Google Scholar
  28. 28.
    Parker JL, Emerson TE (1977) Cerebral hemodynamics, vascular reactivity, and metabolism during canine endotoxin shock. Circ Shock 4:41–53PubMedGoogle Scholar
  29. 29.
    Weiner DE (1970) Effects of endotoxin on cerebral blood flow in the monkey. Am J Physiol 218:160–164PubMedGoogle Scholar
  30. 30.
    Wyler F, Forsyth RP, Nies AS, Neutze JM, Melmon KL (1969) Endotoxin-induced regional circulatory changes in the unanesthetized monkey. Circ Res 24:777–786PubMedCrossRefGoogle Scholar
  31. 31.
    Brian JE, Heistad DD, Faraci FM (1995) Dilatation of cerebral arterioles in response to lipopolysaccharide in vivo. Stroke 26:277–281PubMedCrossRefGoogle Scholar
  32. 32.
    Haberl RL, Anneses F, Ködel U, Pfister HW (1994) Is nitric oxide involved as a mediator of cerebrovascular changes in the early phase of experimental pneumococcal meningitis? Neurol Res 16:108–112PubMedGoogle Scholar
  33. 33.
    Booke M, Meyer J, Lingnau W, Hinder F, Traber LD, Traber DL (1995) Use of nitric oxide synthase inhibitors in animal models of sepsis. New Horiz 3:123–138PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • V. Pollard
  • B. Conroy
  • D. S. Prough
  • D. J. Deyo
  • L. Traber
  • D. Traber

There are no affiliations available

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