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2005 Fiscal Year Final Research Report Summary

Treatment strategy of septic shock by inhibition of transcription factor, NF-kB

Research Project

Project/Area Number 14571423
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MITAKA Chieko  Tokyo Medical and Dental University, Graduate school, Department of Critical Care Medicine, Associate professor, 大学院・医歯学総合研究科, 助教授 (20126254)

Project Period (FY) 2002 – 2005
KeywordsInhibitor of NF-kB / septic shock / endotoxin / multiple organ failure / N2733 / pyrrolidinone derivative
Research Abstract

To investigate whether pyrrolidinone derivative (N2733), an inhibitor of nuclear factor (NF)-kB activation, improves altered metabolic and organ dysfunctions caused by endotoxic shock. Twenty-three anesthetized male beagle dogs were mechanically ventilated and monitored with a pulmonary arterial catheter and a gastric tonometer. A central venous catheter was inserted into the femoral vein, and lactated Ringer's solution (10ml/kg/hr) was administered throughout the study period. Three groups of animals were studied : (a) the lipopolysaccharide (LPS) group (n=8), which received LPS (250ng/kg/min for 2hr) ; (b) the LPS plus N2733 group (n=8), which received N2733 (30mg/kg intravenously and 10mg/kg/hr for 6hr) after the start of LPS ; and (C) the N2733 group (n=7), which received N2733 (30mg/kg intravenously and 10mg/kg/hr for 6hr). Changes in hemodynamic, blood gas, gastric intramural pH, and renal and hepatic function were measured for 6hr. Coadministration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension, metabolic acidosis, and gastric mucosal acidosis but did not affect renal or hepatic function. Administration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension and metabolic and gastric mucosal acidosis in an anesthetized canine endotoxic shock model, suggesting its beneficial effect on local blood flow against tissue hypoxia. These findings suggest that blockade of NF-kB activation prevents hypodynamic shock and gastric hypoperfusion in endotoxic shock.

  • Research Products

    (8 results)

All 2005 2004

All Journal Article (8 results)

  • [Journal Article] Blockade of nuclear factor-κB activation prevents hypodynamic shock and gastric hypoperfusion induced by endotoxin in anesthetized dogs2005

    • Author(s)
      Chieko Mitaka, et al.
    • Journal Title

      Intensive Care Med 31

      Pages: 718-723

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinical laboratory differentiation of infectious versus non-infectious systemic inflammatory response syndrome2005

    • Author(s)
      Chieko Mitaka, et al.
    • Journal Title

      Clinica Chimica Acta 351

      Pages: 17-29

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Blockade of nuclear factor-kB activation prevents hypodynamic shock and gastric hypoperfusion induced by endotoxin in anesthetized dogs2005

    • Author(s)
      Chieko Mitaka, et al.
    • Journal Title

      Intensive Care Med 31

      Pages: 718-723

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical laboratory differentiation of infectious versus non-infectious systemic inflammatory response syndrome2005

    • Author(s)
      Chieko Mitaka
    • Journal Title

      Clinica Chimca Acta 351

      Pages: 17-29

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 病態と疾患からみたNO、敗血症性ショック2004

    • Author(s)
      三高千惠子
    • Journal Title

      日本臨床 62巻 増刊号9

      Pages: 540-543

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 病態と疾患からみたエンドセリン、敗血症性ショック2004

    • Author(s)
      三高千惠子
    • Journal Title

      日本臨床 62巻 増刊号9

      Pages: 661-664

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Septic shock and NO2004

    • Author(s)
      Chieko Mitaka
    • Journal Title

      Nippon Rinsho 62(Suppl 9)

      Pages: 540-543

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Septic shock and endothelin2004

    • Author(s)
      Chieko Mitaka
    • Journal Title

      Nippon Rinsho 62(Suppl 9)

      Pages: 661-664

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2007-12-13  

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