2005 Fiscal Year Final Research Report Summary
Pathophysiology of vasoactive substances and microcirculation disturbance in tissue-factor- or LPS-induced rat DIG models
| Project/Area Number |
16591808
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Kanazawa University Hospital |
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Principal Investigator |
ASAKURA Hidesaku Kanazawa University, Hospital, Associate Professor, 医学部附属病院, 助教授 (60192936)
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| Project Period (FY) |
2004 – 2005
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| Keywords | DIC / endothelin / nitric oxide / tissue factor / lipopolysaccharide |
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| 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.
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Research Products
(12 results)
