| Project/Area Number |
18K16491
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55050:Anesthesiology-related
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| Research Institution | Osaka City University |
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Principal Investigator |
Matsuura Tadashi 大阪市立大学, 大学院医学研究科, 准教授 (90619793)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 局所麻酔薬 / パッチクランプ / 心肥大 / 心筋Naチャネル / 心毒性 |
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| Outline of Final Research Achievements |
Local anesthetics, particularly potent long acting ones, such as bupivacaine, can cause cardiotoxicity by inhibiting sodium (Na+) channels; however, the impact of left ventricular hypertrophy on the cardiotoxicity and the underlying mechanisms remain undetermined. We hypothesized that bupivacaine-induced cardiotoxicity is more severe in left ventricular hypertrophy due to upregulated TRPC channels.
We used a modified transverse aortic constriction model as a left ventricular hypertrophy. Cardiotoxicity caused by bupivacaine was compared between sham and aortic constriction male rats, and the underlying mechanisms were investigated by recording Na+ channel currents and immunocytochemistry of TRPC protein in cardiomyocytes.Left ventricular hypertrophy exacerbated bupivacaine-induced cardiotoxicity, which could be a consequence of the “pore phenomenon” of TRPC3 channels upregulated in left ventricular hypertrophy.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究で左室肥大による局所麻酔薬の心抑制の増悪する機序としてTRPC3チャネルの発現が増加しており、そのTRPC3チャネルのポアをイオン型局所麻酔薬が通過することが示された。
近年の高齢化社会により高齢者が手術を受ける機会が増えている。それに伴い左室肥大を合併した手術患者が増加していると考えられる。そういった高齢者で全身麻酔を避けて末梢神経ブロックや局所浸潤麻酔を選択する機会が増えている。後負荷増大に伴う左室肥大が局所麻酔薬による心抑制作用を増悪させるかはわかっていなかったが、本研究ではそのような患者の局所麻酔薬による心毒性の危険性を示し注意喚起している。
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