Role of Sirtuine in volatile anesthetic-induced postconditioning

• Project/Area Number: 18K16450
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: The University of Tokushima
• Principal Investigator: OYAMA Takuro 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (30792949)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: サーチュイン / イソフルラン / ポストコンディショニング / 心筋保護 / 虚血再灌流障害 / 吸入麻酔薬

Outline of Final Research Achievements

An in vivo model of ischemia-reperfusion injury was tested in anesthetic (isoflurane)-induced postconditioning mice. Mice were randomly assigned to receive anesthetic postconditioning (APostC) with/without sirtuine inhibitor. Biochemical and mitochondrial swelling assays were also performed.
Mice treated with APostC had a significant reduction in infarct size as a percentage of the area at risk compared to controls, whereas mice treated with the sirtuine inhibitor were not protected by APostC. Western blot analysis revealed that sirtuine were increased by APostC. Furthermore, APostC prevented swelling which was reversed by the addition of sirtuine inhibitor.
APostC exhibits a protective effect in myocardial ischemia-reperfusion injury and that sirtuine plays an important role in this postconditioning effects.

Academic Significance and Societal Importance of the Research Achievements

ポストディショニング作用がある様々な薬剤が研究されているが、臨床応用に至っている薬剤は少ない。近年、心筋梗塞リスクを有する患者の周術期管理において吸入麻酔薬が有効であることが示されつつあり、イソフルランのポストコンディショニング作用経路を明らかにすることは、虚血性心疾患のハイリスク患者の安全な周術期管理に寄与すると考えられる。
このことより、虚血性心疾患に対してサーチュインを標的とした新たな治療法の開発を目指した研究基盤の開拓にも貢献する可能性があり、近年わが国においても増加中の虚血性心疾患患者に対する治療戦略として、本研究の成果は非常に重要であると思われる。

Research Products

• [Journal Article] Assessment of postoperative nutritional status and physical function between open surgical aortic valve replacement and transcatheter aortic valve implantation in elderly patients (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Early Diagnosis of the Cardiopulmonary Collapse Type of Amniotic Fluid Embolism with Obstetrical Disseminated Intravascular Coagulation during Elective Cesarean Section : A Case Report (2020)
  • Author(s): Yuki Ishikawa, Yuki Hari, Chiaki Murakami, Yasuhiro Honda, Takuro Oyama, Ryosuke Kawanishi, Nami Kakuta, Yoko Sakai, Takashi Kaji, Yasuo M. Tsutsumi, and Katsuya Tanaka.
  • Journal Title: The Journal of Medical Investigation Volume: 67 Issue: 1.2 Pages: 207-210
  • DOI: 10.2152/jmi.67.207
  • NAID: 130007839805
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Presentation] Glucose transporter-4 mediates acute isoflurane-induced preconditioning in vivo rabbits. (2018)
  • Author(s): Takuro Oyama, Yuta Uemura, Nami Kakuta, Yasuo M. Tsutsumi, and Katsuya Tanaka.
  • Organizer: American Society of Anesthesiologist Annual Meeting
  • Int'l Joint Research