| Project/Area Number |
14571423
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Tokyo Medical and Dental University |
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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)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Inhibitor of NF-kB / septic shock / endotoxin / multiple organ failure / N2733 / pyrrolidinone derivative / NF-κB阻害薬 / pyrrolidine dithiocarbamate / 心筋虚血・再灌流障害 / 誤嚥性肺炎 |
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| 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.
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