| Project/Area Number |
17K11578
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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 | Oita University |
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Principal Investigator |
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 酸化ストレス / カルシウム過負荷 / 心筋障害 / 虚血再灌流 / 電解質 / 低ナトリウム / 心筋虚血再灌流障害 / 活性酸素種 / 低ナトリウム血症 / 虚血再灌流障害 / 慢性心不全 / 細胞内カルシウム過負荷 |
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| Outline of Final Research Achievements |
We investigated the effect of hyponatremia on the ability of the heart to recover from ischemia/reperfusion episodes. Cardiomyocytes were exposed to low sodium concentration (110, 120, or 130 mEq/L) for 72 h. Exposure of cardiomyocytes to each of the low sodium medium significantly increased both of ROS and intracellular Ca2+ levels compared with the exposure to the normal sodium medium. In vivo, 8 week-old male Sprague-Dawley rats were divided into four groups: control group (Con), furosemide group (Fur), low sodium diet group (Lsd), and both furosemide and low sodium diet group (Fur + Lsd). The hearts subjected to global ischemia exhibited considerable decrease in left ventricle developed pressure during reperfusion and the size of infarcts induced by ischemia/reperfusion significantly increased in the Fur, Lsd, and Fur + Lsd compared with those in the Con. Hyponatremia aggravates cardiac susceptibility to ischemia/reperfusion injury by Ca2+ overload and increasing in ROS levels.
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| Academic Significance and Societal Importance of the Research Achievements |
低ナトリウム血症が心不全患者の予後を悪化させる関連性が以前より指摘されていた。今回の研究結果より低ナトリウム濃度への曝露が直接的に心筋細胞に作用し細胞内カルシウム過負荷や活性酸素種増加を介して細胞障害を惹起することを明らかにした。さらに低ナトリウム血症への曝露により虚血再灌流に対する脆弱性が亢進することも見出した。これらの研究結果は低ナトリウム血症の予防と補正が心疾患の発症と増悪の抑制に有効である可能性を強く示唆している。特に虚血性心疾患における心筋ダメージが低ナトリウムにより拡大することから再灌流療法前に介入することで有望な治療ターゲットとなりうると考える。
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