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Cardiac protection by volatile anesthetic -Role of caveolae and mitochondrial regulation-

Research Project

Project/Area Number 19K09353
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionHiroshima University

Principal Investigator

TSUTSUMI Yasuo  広島大学, 医系科学研究科(医), 教授 (90523499)

Co-Investigator(Kenkyū-buntansha) 森尾 篤  広島大学, 病院(医), 助教 (60868389)
三好 寛二  広島大学, 医系科学研究科(医), 助教 (50645364)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords心筋保護作用 / 吸入麻酔薬 / 細胞膜マイクロドメイン / ミトコンドリア / 虚血再灌流障害 / カベオラ・カベオリン / マイクロドメイン
Outline of Research at the Start

近年、吸入麻酔薬やオピオイドなど心筋保護作用をあらわす様々な薬物が報告されており注目を浴びてきた。申請者は吸入麻酔薬によって細胞膜マイクロドメインを介した心筋保護作用が活性化されることを突き止め、重要な役割を担っていることを明らかにしてきた。
また近年の研究によると、ミトコンドリア機能の調節も心筋保護作用に関与していることも明らかになっている。しかし、細胞膜マイクロドメインを介した吸入麻酔薬の心筋保護作用に対してミトコンドリア機能調節がどのように作用するかは明らかではないため、その作用を明らかにする。

Outline of Final Research Achievements

The volatile anesthetic, isoflurane, is known to have the myocardial protective effects, but the full mechanism of this effect is not clear. Additionally, the full contribution of mitochondrial dynamics to cardiac physiology and function remains poorly understood. Using in vivo and in vitro mouse models, this study demonstrated that the cardioprotective effects of volatile anesthetics against ischemia-reperfusion injury are mediated by membrane microdomains, and that mitochondrial dynamics play an important role in the cardioprotective effects as well.

Academic Significance and Societal Importance of the Research Achievements

日本では、ガンが死亡原因の1位であるが、脳卒中・心筋梗塞・心不全・腎不全など心血管障害に基づく死亡はガン以上になると推測される。すでに欧米各国では心血管死亡が非常に多く、また、我が国では超高齢化社会を迎えて加齢による心血管障害が急速に増加しており、その対策は患者自身のQOLや生命予後のみならず、医療経済面からも極めて重要な課題である。申請者は細胞膜マイクロドメインであるカベオラ、カベオリンの影響に注目し、循環器障害について新たな面からアプローチし、そのメカニズムを明らかにしている。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] カリフォルニア大学サンディエゴ校(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Leucine induces cardioprotection in vitro by promoting mitochondrial function via mTOR and Opa-1 signaling.2021

    • Author(s)
      Morio A, Tsutsumi R, Kondo T, Miyoshi H, Kato T, Narasaki S, Satomi S, Nakaya E, Kuroda M, Sakaue H, Kitamura T, Tsutsumi YM
    • Journal Title

      Nutr Metab Cardiovasc Dis

      Volume: 31 Issue: 10 Pages: 2979-2986

    • DOI

      10.1016/j.numecd.2021.06.025

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model.2021

    • Author(s)
      Morio A, Tsutsumi R, Satomi S, Kondo T, Miyoshi H, Kato T, Kuroda M, Kitamura T, Hara K, Saeki N, Sakaue H, and Tsutsumi YM
    • Journal Title

      Diabetol Metab Syndr

      Volume: 13 Issue: 1 Pages: 39-39

    • DOI

      10.1186/s13098-021-00755-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Branched-chain amino acids-induced cardiac protection against ischemia/reperfusion injury.2020

    • Author(s)
      Satomi S, Morio A, Miyoshi H, Nakamura R, Tsutsumi R, Sakaue H, Yasuda T, Saeki N, Tsutsumi YM
    • Journal Title

      Life Science

      Volume: 245 Pages: 117368-117368

    • DOI

      10.1016/j.lfs.2020.117368

    • NAID

      120006993613

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of a new face mask concept for oxygen administration: a crossover study in healthy volunteers.2020

    • Author(s)
      Kondo T, Saeki N, Otsuki S, Tsutsumi YM.
    • Journal Title

      Journal of Anesthesia

      Volume: 34 Issue: 6 Pages: 950-952

    • DOI

      10.1007/s00540-020-02861-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] An outcome study of adult in-hospital cardiac arrests in non-monitored areas with resuscitation attempted using AED.2020

    • Author(s)
      Moriwaki K, Watanabe T, Yasuda M, Katagiri T, Ueki M, Kurita S, Sanuki M, Tsutsumi YM.
    • Journal Title

      Am J Emerg Med

      Volume: 38 Issue: 12 Pages: 2524-2530

    • DOI

      10.1016/j.ajem.2019.12.025

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Propofol induces the elevation of intracellular calcium via morphological changes in intracellular organelles, including the endoplasmic reticulum and mitochondria.2020

    • Author(s)
      Urabe T, Yanase Y, Motoike S, Harada K, Hide I, Tanaka S, Tsutsumi YM, Kawamoto M, Sakai N.
    • Journal Title

      Eur J Pharmacol

      Volume: 884 Pages: 173303-173303

    • DOI

      10.1016/j.ejphar.2020.173303

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of postoperative nutritional status and physical function between open surgical aortic valve replacement and transcatheter aortic valve implantation in elderly patients2020

    • Author(s)
      Mayu Sebe, Rie Tsutsumi, Takuro Oyama, Yousuke T. Horikawa, Yuta Uemura, Nami Kakuta, Yoko Sakai, Atsushi Morio, Hirotsugu Miyoshi, Takashi Kondo, Tomoaki Urabe, Yuko Noda, Satoshi Kamiya, Noboru Saeki, Masashi Kuroda, Katsuya Tanaka, Yasuo M. Tsutsumi, and Hiroshi Sakaue.
    • Journal Title

      The Journal of Medical Investigation

      Volume: 67 Issue: 1.2 Pages: 139-144

    • DOI

      10.2152/jmi.67.139

    • NAID

      130007839863

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Postoperative nausea and vomiting following lower limb surgery :a comparison between single-injection intraarticular anesthesia and continuous epidural anesthesia2019

    • Author(s)
      Yuta Uemura, Yoko Sakai, Yasuo M. Tsutsumi, Nami Kakuta, Chiaki Murakami, Shiho Satomi, Takuro Oyama, Naohiro Ohshita, Tomoya Takasago, Daisuke Hamada, Koichi Sairyo, and Katsuya Tanaka.
    • Journal Title

      The Journal of Medical Investigation

      Volume: 66 Issue: 3.4 Pages: 303-307

    • DOI

      10.2152/jmi.66.303

    • NAID

      130007733031

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monitoring of muscle mass in critically ill patients: comparison of ultrasound and two bioelectrical impedance analysis devices.2019

    • Author(s)
      Nobuto Nakanishi, Rie Tsutsumi, Yoshihiro Okayama, Takuya Takashima, Yoshitoyo Ueno, Taiga Itagaki, Yasuo Tsutsumi, Hiroshi Sakaue, and Jun Oto.
    • Journal Title

      Journal of Intensive Care

      Volume: 7 Issue: 1 Pages: 61-61

    • DOI

      10.1186/s40560-019-0416-y

    • NAID

      120006939635

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Pleth variability index predicts hemodynamic derangements in patients undergoing oral surgery.2019

    • Author(s)
      Kazumi Takaishi, Tomohiro Aoyama, Shigeki Fujiwara, Ryo Otsuka, Satoru Eguchi, Yasuo M. Tsutsumi, Shinji Kawahito, Hiroyuki Kinoshita, and Hiroshi Kitahata.
    • Organizer
      American Society of Anesthesiologist Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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