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Platelet and vascular endothelial function in the pathogenesis of acquired VW disease after VAD therapy

Research Project

Project/Area Number 17K10745
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular surgery
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

MIZUNO Toshihide  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40426515)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords補助人工心臓 / 後天性フォンビルブランド病 / 血小板機能 / 血管内皮機能 / 血液凝固能 / von Wllebrand factor / 重症心不全 / せんだん応力 / 高分子量マルチマー / 定常流型補助人工心臓 / フォンビルブランド因子 / ADAMTS13 / 後天性VW病
Outline of Final Research Achievements

In this study, A simple mock circulation test (5L/min, 100 mmHg) was performed to investigate with both whole-blood samples and platelet-poor plasma (PPP) using fresh bovine blood. High-molecular-weight multimers (HMWMs) in VWF are reduced immediately after the initiation of blood circulation using the axial flow pump, and it had plateaued 60 minutes later. In the study using a centrifugal pump, cleavage of the HMWMs compared to that in the case of using a centrifugal pump was very slight. Moreover, in the whole-blood sample study, HMWMs reduced once, and it had been observed to recover after 60 minutes. However, HMWMs in the PPP sample was observed to reduce continuously during a circulation test. The dynamics of VWF within the blood pump was shown to depend on the type of the blood pump, and this study demonstrated that re-supply of VWF due to platelet activation and cleavage of VWF due to shear stress in the pump occurred at the same time by circulating within the blood pump.

Academic Significance and Societal Importance of the Research Achievements

VAD装着後の後天性VW病は,術後遠隔期の出血性素因として注目されているが,その病理学的機序は明らかになっていない.現在までの研究では,この後天性VW病におけるVWF高分子量マルチマーの切断現象に関してポンプ内の物理的要因による機序に注目が集まっているが,その病態の多様性を考慮すると,生体内からのVWFの再供給が本病態に大きく係わっていることが新たに予想された.しかしながら,このような観点での研究は,現時点ではほとんどされておらず,本研究によりVAD装着後の出血性合併症の本態が解明され,成果が患者へ還元されれば,VAD症着後の出血性合併症の診断,治療に大きく寄与できるものと考えた.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (10 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Cleavage and Re-Supply of von Willebrand Factor in Continuous Flow Blood Pump2019

    • Author(s)
      Mizuno, T. Eura, Y. Kokame, K. Tsukiya, T. Takewa, Y. Tatsumi, E.
    • Journal Title

      Journal of Heart and Lung Transplantation

      Volume: 38 Issue: 4 Pages: S428-S429

    • DOI

      10.1016/j.healun.2019.01.1093

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel Extracorporeal Continuous-Flow Ventricular Assist System for Patients with Advanced Heart Failure2019

    • Author(s)
      Seguchi O.、Fujita T.、Kumai Y.、Kuroda K.、Nakajima S.、Watanabe T.、Yanase M.、Matsumoto Y.、Fukushima S.、Tsukiya T.、Mizuno T.、Katagiri N.、Kakuta Y.、Takewa Y.、Hamasaki T.、Yamamoto H.、Tatsumi E.、Kobayashi J.、Fukushima N.
    • Journal Title

      The Journal of Heart and Lung Transplantation

      Volume: 38 Issue: 4 Pages: S344-S344

    • DOI

      10.1016/j.healun.2019.01.871

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differences in clotting parameters between species for preclinical large animal studies of cardiovascular devices2018

    • Author(s)
      Mizuno Toshihide、Tsukiya Tomonori、Takewa Yoshiaki、Tatsumi Eisuke
    • Journal Title

      Journal of Artificial Organs

      Volume: 21 Issue: 2 Pages: 138-141

    • DOI

      10.1007/s10047-017-1003-4

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Cleavage and Re-Supply of von Willebrand Factor in Continuous Flow Blood Pump2019

    • Author(s)
      Mizuno, T. Eura, Y. Kokame, K. Tsukiya, T. Takewa, Y. Tatsumi, E.
    • Organizer
      ISHLT2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cleavage and Re-Supply of von Willebrand Factor in Continuous Flow Blood Pump2019

    • Author(s)
      Mizuno T.、Eura Y.、Kokame K.、Tsukiya T.、Takewa Y.、Tatsumi E.
    • Organizer
      39th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大型実験動物における血液の凝固特性の違いについて2018

    • Author(s)
      水野, 敏秀 築谷, 朋典 武輪, 能明 巽, 英介
    • Organizer
      第40回日本バイオマテリアル学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 人工臓器開発における非臨床試験 動物種間における血液凝固特性の違いについて2018

    • Author(s)
      水野, 敏秀 築谷, 朋典 武輪, 能明 巽, 英介
    • Organizer
      第56回日本人工臓器学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Differences in fibrin metabolism among the species for preclinical large animal models for cardiovascular device2018

    • Author(s)
      Toshihide Mizuno, Tomonori Tsukiya, Toshiaki Takewa, Eisuke Tatsumi
    • Organizer
      38th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大型実験動物における血液の凝固特性の違いについて2018

    • Author(s)
      水野敏秀,築谷朋典,武輪能明,巽英介
    • Organizer
      第57回日本生体医工学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Comparisons in Clotting Parameters Between Species for Preclinical Animal Studies2017

    • Author(s)
      Toshihide Mizuno, Tomonori Tsukiya, Toshiaki Takewa, Eisuke Tatsumi
    • Organizer
      37th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effect of storage or anticoagulation condition of bovine blood for evaluating blood damage in blood pump testing2017

    • Author(s)
      Toshihide Mizuno, Tomonori Tsukiya, Toshiaki Takewa, Eisuke Tatsumi
    • Organizer
      1st International Society for Mechanical Circulatory Support
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 溶血試験における新鮮血と市販保存血使用時の差異に関する研究2017

    • Author(s)
      水野敏秀,築谷朋典,武輪能明,巽英介
    • Organizer
      第55回日本人工臓器学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 連続流血液ポンプ使用時におけるvon Willebrand factorの動態2017

    • Author(s)
      水野敏秀,築谷朋典,武輪能明,巽英介
    • Organizer
      第45回人工心臓と補助循環懇話会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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