| Project/Area Number |
14370495
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Keio University |
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Principal Investigator |
MORISAKI Hiroshi Keio University, School of Medicine, Associate Professor, MD, 医学部, 助教授 (60182226)
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| Co-Investigator(Kenkyū-buntansha) |
KOTAKE Yoshifumi Keio University, School of Medicine, Assistant Professor, MD, 医学部, 講師 (70195733)
MORITA Yoshihisa Keio University, School of Medicine, Instructor, MD, 医学部, 助手 (10276983)
末松 誠 慶應義塾大学, 医学部, 教授 (00206385)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | Sepsis / Transfusion / Microcirculation / Hemoglobin / Gut barrier function / Nitric oxide / Carbon monoxide / 内毒素血症 / ヘムオキシゲナーゼ |
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| Research Abstract |
We tested the hypothesis that heme loading by blood transfusion was harmful for the host defense system like gut barrier function under the conditions where heme oxygenase-1 (HO-1) was induced. Using endotoxemic rat model, we first examined the effects of hemoglobin level, high (13-16g/dl) versus low (7-9 g/dl) by isovolemic transfusion or hemodilution, respectively, on the permeability of gut barrier, and found that high level of hemoglobin augmented the increased permeability of gut in endotoxemic rats compared with low-hemoglobin. To text the involvement of HO-1 in this finding, we then examined the same effects of hemoglobin level in HO-1 induced rats. However, both blood transfusion and hemodilution in rats treated with intraperitoneal hemin injection to induce HO-1 caused all death within 16 hours. Besides, immunohistochemistry of HO-1 on gut mucosa showed no augmentation in both high and low hemoglobin rats. Taken together, NO-1 is unlikely to contribute to the development of high-hemoglobin-induced, the elevation of gut mucosal permeability, in endotoxemia. Using an intravital microscopy to observe gut mucosal microcirculation, we then found that intramucosal microcirculation was retarded and capillary density was reduced in the high hemoglobin group in healthy rats. In addition, high-hemoglobin augmented to-and-fro phenomenon observed in endotoxemic rats whereas no significant changes were observed in low-hemoglobin group. Superfusion with NO donor ameliorated the mucosal microcirculation and inhibition of NO synthase with L-NAME deteriorated the microcirculation irrespectively of hemoglobin level. Given these data, NO is a significant regulator of gut mucosal permeability in endotoxemia with focus on the effects high hemoglobin level.
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