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Control of apoptosis in septic cardiomyopathy and elucidation of the role of GLP-1 receptor

Research Project

Project/Area Number 18K08921
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionNagasaki University

Principal Investigator

YOSHITOMI Osamu  長崎大学, 病院(医学系), 准教授 (30380926)

Co-Investigator(Kenkyū-buntansha) 関野 元裕  長崎大学, 病院(医学系), 准教授 (40380927)
Project Period (FY) 2018-04-01 – 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 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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords集中治療 / 心筋虚血 / GLP-1受容体 / SGLT2 阻害薬 / α2受容体作動薬 / 敗血症 / 心筋収縮力 / 糖尿病治療薬 / 敗血症性ショック / 心筋拡張障害 / アポトーシス / 敗血症性心筋障害
Outline of Final Research Achievements

In this study, we investigated the protective effects and mechanisms of sedatives, circulatory agonists, and diabetes treatments used in intensive care using a biocirculatory insufficiency model under general anesthesia of animals.
It was suggested that pre-ischemic or post-reperfusion intravenous administration of GLP-1 receptor agonists improves the recovery of contractility after myocardial ischemia-reperfusion in pigs. SGLT1 inhibition diminishes the cardioprotective effect of IPC through suppression of p-AMPK, whereas SGLT2 inhibitors do not affect the cardioprotective effect. It was also suggested that the cardioprotective effect of phosphodiesterase Ⅲ inhibitors is not affected by SGLT1 inhibition. It was suggested that α2 receptor agonists stabilize hemodynamics after successful resuscitation and improve cardiac output compared to epinephrine.

Academic Significance and Societal Importance of the Research Achievements

敗血症や心肺蘇生後など集中治療を要する重症患者の死亡率は、集中治療医学の著しい進歩にもかかわらず、依然として高い。重症患者の循環動態は心筋収縮および拡張障害を伴い、その結果として臓器障害のリスクを増加させる。心筋収縮および拡張障害に対する効果的な保護治療を施すことは、予後改善にも繋がる。
一方、実際の臨床における集中治療では、鎮静薬や循環作動薬、糖尿病治療薬など多くの薬剤を使用しているのが現状である。より臨床に即した動物の全身麻酔下生体モデルを用いること、また各病態における各種薬剤の保護作用およびその機序について検討することにより、集中治療における適切な薬剤選択を可能とする。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (2 results)

All 2021

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results)

  • [Journal Article] Tracheobronchial Stent Insertion Under Venovenous Extracorporeal Membrane Oxygenation in a Patient With Coronavirus Disease 20192021

    • Author(s)
      Ichinomiya Taiga、Murata Hiroaki、Sekino Motohiro、Yokoyama Haruka、Ogami-Takamura Keiko、Higashijima Ushio、Ashizawa Nobuyuki、Izumikawa Koichi、Machino Ryusuke、Matsumoto Keitaro、Nakaji Shun、Yoshitomi Osamu、Hara Tetsuya
    • Journal Title

      Journal of Cardiothoracic and Vascular Anesthesia

      Volume: - Issue: 8 Pages: 1-5

    • DOI

      10.1053/j.jvca.2021.09.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] 蘇生後心筋障害に対するデクスメデトミジンの効果―豚の心肺蘇生モデルを用いた検討―2021

    • Author(s)
      吉富 修、新谷亮祐、飛永祥平、一ノ宮大雅、原 哲也
    • Organizer
      日本循環制御医学会
    • Related Report
      2021 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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