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2005 Fiscal Year Final Research Report Summary

Pathophysiology of vasoactive substances and microcirculation disturbance in tissue-factor- or LPS-induced rat DIG models

Research Project

Project/Area Number 16591808
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionKanazawa University Hospital

Principal Investigator

ASAKURA Hidesaku  Kanazawa University, Hospital, Associate Professor, 医学部附属病院, 助教授 (60192936)

Project Period (FY) 2004 – 2005
KeywordsDIC / endothelin / nitric oxide / tissue factor / lipopolysaccharide
Research Abstract

Disseminated intravascular coagulation (DIC) is induced by tissue-factor (TF) or lipopolysaccharide (LPS) in rats. Our previous studies have demonstrated that TF-induced DIC mimics clinical DIC with enhanced fibrinolysis and LPS-induced DIC mimics clinical DIC with suppressed fibrinolysis. In this time, we have investigated the pathophysiology of DIC from the point of vasoactive substances. Plasma levels of endothelin (ET) were markedly increased in LPS-induced DIC but not at all in TF-induced DIC. On the other hand, plasma levels of NOX (metabolites of nitric oxide) were moderately increased in the former and markedly increased in the latter. Moreover, ET receptor antagonist improved organ dysfunction and glomerular fibrin deposition in LPS-induced DIC, while had no effect on the pathophysiology in TF-induced DIC. Thus, it was suggested that ET plays an important role in LPS-induced DIC. An inducible NO synthase inhibitor (L-NIL) improved organ dysfunction, glomerular fibrin deposition and depressed blood pressure, which could demonstrate that NO also plays an important role in LPS-induced DIC. In the last, PGI2 antagonist suppressed plasma levels of proinflammatory cytokines such as TNF and IL-6, and improved hemostatic markers, organ dysfunction and glomerular fibrin deposition. PGI2 antagonist suppressed plasma levels of NOX but not ET. These results suggest that the modulator of vasoactive substances or proinflammatory cytokines may be novel therapeutic methods in future.

  • Research Products

    (12 results)

All 2006 2005

All Journal Article (12 results)

  • [Journal Article] Evaluation of haemostatic molecular markers for diagnosis of disseminated intravascular coagulation in patients with infections2006

    • Author(s)
      Asakura H, Wada H, et al.
    • Journal Title

      Thromb Haemost 95・2

      Pages: 282-287

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of sarpogrelate hydrochloride in a patient with chronic graft-versus-host disease2006

    • Author(s)
      Hayashi T, Asakura H, et al.
    • Journal Title

      Am J Hematol 91・2

      Pages: 121-123

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Evaluation of haemostatic molecular markers for diagnosis of disseminated intravascular coagulation in patients with infections2006

    • Author(s)
      Asakura H, Wada H, et al.
    • Journal Title

      Thromb Haemost 95(2)

      Pages: 282-287

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of sarpogrelate hydrochloride in a patient with chronic graft-versus-host disease2006

    • Author(s)
      Hayashi T, Asakura H, et al.
    • Journal Title

      Am J Hematol 91(2)

      Pages: 121-123

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Kasabach-Merritt syndrome associated with giant liver hemangioma : the effect of combined therapy with danaparoid sodium and TA2005

    • Author(s)
      Ontachi Y, Asakura H, et al.
    • Journal Title

      Haematologica 90

      Pages: ECR 29

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of combined therapy of danaparoid sodium and tranexamic acid on chronic DIC associated with abdominal aortic aneurysm2005

    • Author(s)
      Ontachi Y, Asakura H, et al.
    • Journal Title

      Circ J 69・9

      Pages: 1150-1153

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Selective iNOS inhibition attenuates organ dysfunction and elevated endothelin levels in LPS-induced DIC model rats2005

    • Author(s)
      Asakura H, Asamura R, et al.
    • Journal Title

      J Thromb Haemost 3・5

      Pages: 1050-1055

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Beneficial effects of urokinase on LPS-induced DIC in rats : focus on organ function and endothelin levels2005

    • Author(s)
      Asakura H, Asamura R, et al.
    • Journal Title

      Thromb Haemost 93・4

      Pages: 724-728

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Kasabach-Merritt syndrome associated with giant liver hemangioma : the effect of combined therapy with danaparoid sodium and TA2005

    • Author(s)
      Ontachi Y, Asakura H, et al.
    • Journal Title

      Haematologica 90:ECR29

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of combined therapy of danaparoid sodium and tranexamic acid on chronic DIC associated with abdominal aortic aneurysm2005

    • Author(s)
      Ontachi Y, Asakura H, et al.
    • Journal Title

      Circ J 69(9)

      Pages: 1150-1153

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Selective iNOS inhibition attenuates organ dysfunction and elevated endothelin levels in LPS-induced DIC model rats2005

    • Author(s)
      Asakura H, Asamura R, et al.
    • Journal Title

      J Thromb Haemost 3(5)

      Pages: 1050-1055

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Beneficial effects of urokinase on LPS-induced DIG in rats : focus on organ function and endothelin levels2005

    • Author(s)
      Asakura H, Asamura R, et al.
    • Journal Title

      Thromb Haemost 93(4)

      Pages: 724-728

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

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Published: 2007-12-13  

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