| Project/Area Number |
17K11599
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
室谷 卓 関西医科大学, 医学部, 講師 (20528434)
池側 均 関西医科大学, 医学部, 准教授 (80379198)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 敗血症ショック / ノルアドレナリン / ランジオロール / 上腸間膜静脈血流 / 空腸粘膜組織血流 / sepsis / splanchnic circulation / circulatory shock / randiolol / noradrenaline / 敗血症性ショック / endotoxin / 腸管粘膜血流 / LPS / blood flow / beta adrenergic receptor / oxygen delivery / oxygen metabolism |
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| Outline of Final Research Achievements |
The present study was designed to evaluate the effect of continuous infusion of noradrenaline (NAD) or landiolol on systemic hemodynamics and mucosal blood flow in gut during experimental sepsis in rabbits. Single intravenous administration of LPS (1mg/kg body weight) reproduced hemodynamic change in human sepsis, characterized by decreased systemic vascular resistance (SVR) and consistent cardiac output. LPS also significantly increased blood flow in superior mesenteric vein (SMV), in the presence of paradoxical decrease in mucosal blood flow. Continuous infusion of NAD at a dosage of 2.0 microgm/kg/hr restored both SVR and blood flow in SMV to normal level, but ischemia of the intestinal mucosa sustained, or otherwise deteriorated. Various dosage of landiolol was tested to improve hemodynamics and/or abnormal circulatory state in splanchnic circulation occurred in the present animal model. However, no significant effect was observed during the study period at any dosage of landiolol.
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| Academic Significance and Societal Importance of the Research Achievements |
LPS誘導ウサギ敗血症ショックモデルにおいて、現在血管作動薬として第一選択であるNAD持続静脈内投与は腸管循環系の血管抵抗を是正し、体循環系の動脈圧を是正する効果を有することが明らかとなった。一方でNAD投与は、腸管粘膜血流低下を是正せず、あるいはさらに低下させる効果を有し、むしろ腸管虚血を来す可能性が示唆された。本モデルは臨床を禁じしたマクロ生理学モデルとして敗血症時の腸管循環系血行動態異常や、ひいては非閉塞性腸管虚血症をきたす機序を解明するための格好のツールとなり得ることが示唆された。
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