Experimental Models of Source Control

  • Wang Ping
  • Irshad H. Chaudry
Chapter

Abstract

• Various animal models such as for endotoxemia, endotoxic shock, or bacteremia have been used to study the pathobiology of sepsis, and such models provided useful information regarding the mechanism of cell and organ dysfunctions under those conditions. However, those models do not permit control of the source of infection. • A number of investigators have used cecal ligation and puncture (CLP) in various species to produce polymicrobial sepsis. The CLP model of sepsis mimics many features of clinical peritonitis, including the progressive changes in cardiovascular responses (i.e., an early hyperdynamic phase followed by a late hypodynamic phase). • The CLP model of sepsis is associated with cellular dysfunction (such as hepatocellular depression) and upregulation of proinflammatory cytokines (such as TNF). Furthermore, the ligated and punctured cecum can be excised at various intervals to serve as a source control model of sepsis. Such a model can be used for testing pharmacological agents in the management of sepsis.

Keywords

Depression Heparin Gelatin Adenine Peritonitis 

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References

  1. 1.
    Baue AE, Durham R, Faist E (1998) Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF): are we winning the battle? Shock 10:79–89PubMedCrossRefGoogle Scholar
  2. 2.
    Tracey KJ, Abraham E (1999) From mouse to man: or what have we learned about cytokine-based anti-inflammatory therapies? Shock 11:224–225PubMedCrossRefGoogle Scholar
  3. 3.
    Teplick R, Rubin R (1999) Therapy of sepsis: why have we made such little progress? Crit Care Med 27:1682–1683PubMedCrossRefGoogle Scholar
  4. 4.
    Fink MP, Heard SO (1990) Laboratory models of sepsis and septic shock. J Surg Res 49:186–196PubMedCrossRefGoogle Scholar
  5. 5.
    Deitch EA (1998) Animal models of sepsis and shock: a review and lessons learned. Shock 9:1–11PubMedCrossRefGoogle Scholar
  6. 6.
    Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251PubMedCrossRefGoogle Scholar
  7. 7.
    Wichterman KA, Baue AE, Chaudry IH (1980) Sepsis and septic shock: a review of laboratory models and a proposal. J Surg Res 29:189–201PubMedCrossRefGoogle Scholar
  8. 8.
    Yang S, Hauptman JG (1994) The efficacy of heparin and antithrombin III in fluid-resuscitated cecal ligation and puncture. Shock 2:433–437PubMedCrossRefGoogle Scholar
  9. 9.
    Hadjiminas DJ, McMasters KM, Robertson SE, Cheadle WG (1994) Enhanced survival from cecal ligation and puncture with pentoxifylline is associated with altered neutrophil trafficking and reduced interleukin-1b expression but not inhibition of tumor necrosis factor synthesis. Surgery 116:348–355PubMedGoogle Scholar
  10. 10.
    Chaudry IH, Wichterman KA, Baue AE (1979) Effect of sepsis on tissue adenine nucleotide levels. Surgery 85:205–221PubMedGoogle Scholar
  11. 11.
    Wang P, Chaudry IH (1996) Mechanism of hepatocellular dysfunction during hyperdynamic sepsis. Am J Physiol 270:R927-R938Google Scholar
  12. 12.
    Ayala A, Chaudry IH (1996) Immune dysfunction in murine polymicrobial sepsis: mediators, macrophages, lymphocytes and apoptosis. Shock 6[Suppl]:S27–S38PubMedGoogle Scholar
  13. 13.
    Fox GA, Lam CJ, Darragh WB, Neal AM, Inman KJ, Rutledge FS, Sibbald WJ (1996) Circulatory sequelae of administering CPAP in hyperdynamic sepsis are time dependent. J Appl Physiol 81:976–984PubMedGoogle Scholar
  14. 14.
    Stahl TJ, Alden PB, Ring WS, Madoff RC, Cerra FB (1990) Sepsis-induced diastolic dysfunction in chronic peritonitis. Am J Physiol 258:H625–H633PubMedGoogle Scholar
  15. 15.
    Yang S, Cioffi WG, Bland KI, Chaudry IH, Wang P (1999) Differential alterations in systemic and regional oxygen delivery and consumption during the early and late stages of sepsis. J Trauma 47:706–712PubMedCrossRefGoogle Scholar
  16. 16.
    Wang P, Ba ZF, Chaudry IH (1995) Hepatocellular dysfunction occurs earlier than the onset of hyperdynamic circulation during sepsis. Shock 3:21–26PubMedGoogle Scholar
  17. 17.
    Wang P, Ayala A, Ba ZF, Zhou M, Perrin MM, Chaudry IH (1993) Tumor necrosis factor-a produces hepatocellular dysfunction despite normal cardiac output and hepatic microcirculation. Am J Physiol 265:G126–G132PubMedGoogle Scholar
  18. 18.
    Witek-Janusek L, Ratmeyer JK (1991) Sepsis in the young rat: maternal milk protects during cecal ligation and puncture sepsis but not during endotoxemia. Circ Shock 33:200–206PubMedGoogle Scholar
  19. 19.
    Remick D, Manohar P, Bolgos G, Rodriguez J, Moldawer L, Wollenberg G (1995) Blockade of tumor necrosis factor reduces lipopolysaccharide lethality, but not the lethality of cecal ligation and puncture. Shock 4:89–95PubMedCrossRefGoogle Scholar
  20. 20.
    Ozmen V, Thomas WO, Healy JT et al (1993) Irrigation of the abdominal cavity in the treatment of experimentally induced microbial peritonitis: efficacy of ozonated saline. Am Surg 59:297–303PubMedGoogle Scholar
  21. 21.
    Ahrenholz DH, Simmons RL (1980) Fibrin in peritonitis. I. Beneficial and adverse effects of fibrin in experimental E. coli peritonitis. Surgery 88:41–47Google Scholar
  22. 22.
    Nelson JL, Alexander JN, Mao JX et al (1999) Effect of pentoxifylline on survival and intestinal cytokine messenger RNA transcription in a rat model of ongoing peritoneal sepsis. Crit Care Med 27:113–119PubMedCrossRefGoogle Scholar
  23. 23.
    Kinasewitz GT, Chang AC, Peer GT et al (2000) Peritonitis in the baboon: a primate model which stimulates human sepsis. Shock 13:100PubMedCrossRefGoogle Scholar
  24. 24.
    Mela-Riker L, Bartos D, Vlessis AA et al (1988) Chronic hyperdynamic sepsis in the rat. Circ Shock 25:231–244PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • Wang Ping
  • Irshad H. Chaudry

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