| Project/Area Number |
16K10941
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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 |
Anesthesiology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TANAKA Katsuya 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (30263841)
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| Co-Investigator(Kenkyū-buntansha) |
堤 保夫 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (90523499)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 吸入麻酔薬 / イソフルラン / 心筋保護効果 / グルコース輸送体 / 心筋虚血再灌流傷害 / グルコース輸送体４ / グルコース取り込み / リトナビル / 糖輸送担体 |
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| Outline of Final Research Achievements |
Involvement of glucose transporter-4 (GLUT4) in acute anesthetic preconditioning (APC) is unknown. We tested the hypothesis that inhibition of GLUT4 abolished the mocardial protective effects of acute isoflurane-induced preconditioning. Pentobarbital-anesthetized rabbits were instrumented to measure hemodynamics. All rabbits were subjected to a 30 min coronary artery occlusion followed by 3-h reperfusion. Rabbits were randomly assigned to receive 0.9% saline or the nonselective GLUT4 inhibitor ritonavir in the presence or absence of 1 MAC isoflurane. At the end of each experiments the heart was removed and infarct size was measured. As the results, isoflurane significantly reduced infarct size as compared to control experiments. Ritonavir abolished the cardioprotective effects of isoflurane, while ritonavir alone had no effect on myocardial infarct size. These results suggest that enhanced mocardial glucose uptake through GLUT4 during reperfusion may be an essential part of acute APC.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究の結果から、吸入麻酔薬による心筋保護効果の作用機序にグルコース輸送体４を介するグルコースの取り込みが再灌流時に行われることが重要であることが示唆される。吸入麻酔薬の心筋保護効果の作用機序解明は、今後高齢者が増加する日本で周術期の虚血性心疾患の発生を抑制することが可能となり安全な周術期管理を行うことの一つの選択肢となりうる。また、麻酔薬による心筋保護効果の作用機序解明は、周術期の患者管理のみならず、虚血性心疾患を予防するための新薬開発の一助となる可能性も秘めている。
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