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Vasopressor-induced attenuation of endothelial glycocalyx degradation by hydroxyethyl starch

Research Project

Project/Area Number 19K09363
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Tatara Tsuneo  兵庫医科大学, 医学部, 教授 (30207039)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsグリコカリックス / ヒドロキシエチルデンプン / ヒアルロン酸 / ずり / ヒドロキシエチルスターチ / 分配係数
Outline of Research at the Start

手術侵襲時の血漿量維持のために使用されるヒドロキシエチルデンプン(HES)製剤は、炎症時には血管内皮細胞表面のグリコカリックスを崩壊させることにより臓器不全をきたす。このHES製剤がもたらす組織障害のため、現在、HES製剤の臨床使用に大きな混乱が生じている。本研究では、グリコカリックスが柔軟なゲルであることをヒントにして、血管収縮薬の併用が手術侵襲時におけるHES製剤の組織障害を軽減する可能性を検討することにより、HES製剤の臨床使用に新たな活路を見出す。

Outline of Final Research Achievements

Hydroxyethyl starch (HES) solution, widely used to correct the decrease of blood volume during surgery, degrades the endothelial glycocalyx. This research aimed to test the hypothesis that vasopressor attenuates degradation of endothelial glycocalyx by HES. The HES increased storage and loss shear moduli of hyaluronate solution, suggesting that HES strengthens the transient hyaluronate network by creating new hydrogen bonds. Plasma volume increase following HES infusion after the induction of general anesthesia was larger in the vasopressor group. There were no clinically significant differences in plasma concentrations of hyaluronate between the groups. Increased volume expansion of circulating plasma following HES infusion in anesthesia-induced hypotension compared to when blood pressure is restored by phenylephrine may result from an attenuation of transcapillary fluid filtration, rather than the shedding of glycocalyx.

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、重症患者においてHES製剤の過剰投与を回避し、適切なタイミングでHES製剤を投与するためのHES製剤の安全かつ効果的な使用に新たな活路を見出したと考えている。この結果は、敗血症など致死率の高い重症患者の予後を改善する一助となるため、社会に大きく貢献すると期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 3 results)

  • [Journal Article] Different effects of albumin and hydroxyethyl starch on low molecular-weight solute permeation through sodium hyaluronic acid solution.2021

    • Author(s)
      Tatara T
    • Journal Title

      Polymers

      Volume: 13 Issue: 4 Pages: 514-525

    • DOI

      10.3390/polym13040514

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complex effects of continuous vasopressor infusion on fluid responsiveness during liver resection. A randomised controlled trial.2019

    • Author(s)
      Nakamoto S, Tatara T, Okamoto T, Hirose M.
    • Journal Title

      European Journal of Anaesthesiology

      Volume: 36 Issue: 9 Pages: 667-675

    • DOI

      10.1097/eja.0000000000001046

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] からだの中のソフトマター2022

    • Author(s)
      多田羅恒雄
    • Organizer
      第40回日本麻酔・集中治療テクノロジー学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] グリコカリックスからみた輸液の生理学2022

    • Author(s)
      多田羅 恒雄
    • Organizer
      第49回日本集中治療医学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 何を考えて輸液をする?2021

    • Author(s)
      多田羅恒雄
    • Organizer
      第48回日本集中治療医学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2024-01-30  

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