• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Basic research for development of hemorrhagic complication therapeutic drug by long-term use of mechanical circulation

Research Project

Project/Area Number 19K12772
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionAsahikawa Medical College (2020-2022)
Tohoku University (2019)

Principal Investigator

Inoue Yusuke  旭川医科大学, 医学部, 准教授 (80611079)

Co-Investigator(Kenkyū-buntansha) 早川 正樹  奈良県立医科大学, 医学部, 助教 (30516729)
深谷 碧  東北文化学園大学, 工学部, 助教 (20826060)
山田 昭博  東北大学, 加齢医学研究所, 助教 (40781448)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsVWF / 出血合併症 / ECMO / PCPS / LVAD / 遠心ポンプ / ADAMTS13 / 出血 / 機械循環 / 補助人工心臓 / 血栓 / せん断 / 血液ポンプ / 模擬循環回路 / 人工心臓 / 流体解析
Outline of Research at the Start

補助人工心臓を数年間適用すると正しい抗凝固療法下でも出血合併症が生じる。その主因は後天性von Willebrand 症候群(AVWS)と考えられており、血液ポンプの回転駆動よって発生した高せん断によりvon Willebrand因子(VWF)が過剰に切断され、出血に至る。我々はVWFの切断を抑制し、出血を生じさせない薬剤の開発を進めているが、適切な薬剤濃度などの治療法と評価方法は確立されておらず、臨床ステージに進むにあたって取り組むべき急務の課題となっている。そこで本研究では、血液ポンプの長期使用時の合併症に対する治療法の開発とその作用機序の解明を目的として研究を行う。

Outline of Final Research Achievements

Acquired von Willebrand syndrome (AVWS) is thought to be the cause of bleeding complications that can occur after several years of use of an artificial heart. It is believed that high shear of the blood pump leads to excessive cleavage of von Willebrand factor (VWF), resulting in bleeding. The purpose of this study was to elucidate the mechanism of action of this bleeding complication. We constructed an evaluation system with minimal disturbance and reproduced AVWS in vitro by injecting fresh human blood into an auxiliary circulatory system. Next, drug effects were measured and effective drug concentrations were identified.

Academic Significance and Societal Importance of the Research Achievements

抗凝固が正しく管理されているにもかかわらず機械循環の使用例において数年以上の長期使用においては原因不明の出血が生じることがあり、問題視されてきた。その主因は後天性von Willebrand 症候群(AVWS)と考えられており、血液ポンプの回転駆動よって発生した高せん断によりvon Willebrand因子(VWF)が過剰に切断され、出血に至る。我々はVWFの切断を抑制し、出血を生じさせない薬剤の開発のために、外乱が最も少ない試験系を構築することに成功した。本試験系によって得られた知見を元に生体によって評価しAVWS治療薬剤開発のための大きな成果を得た。

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

    (32 results)

All 2023 2022 2021 2020 2019

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 3 results) Presentation (17 results) (of which Int'l Joint Research: 1 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Prevention of thrombus formation in blood pump by mechanical circular orbital excitation of impeller in magnetically levitated centrifugal pump2023

    • Author(s)
      Hatakenaka Kohei, Hijikata Wataru, Fujiwara Tatsuki, Ohuchi Katsuhiro, Inoue Yusuke
    • Journal Title

      Artificial Organs

      Volume: 47 Issue: 2 Pages: 425-431

    • DOI

      10.1111/aor.14443

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Innovative experimental animal models for real-time comparison of antithrombogenicity between two oxygenators using dual extracorporeal circulation circuits and indocyanine green fluorescence imaging2023

    • Author(s)
      Sakurai Hironobu, Fujiwara Tatsuki, Ohuchi Katsuhiro, Hijikata Wataru, Inoue Yusuke, Maruyama Osamu, Tahara Tomoki, Yokota Sachie, Tanaka Yui, Takewa Yoshiaki, Mizuno Tomohiro, Arai Hirokuni
    • Journal Title

      Artificial Organs

      Volume: 47 Issue: 1 Pages: 77-87

    • DOI

      10.1111/aor.14380

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development and initial performance of a miniature axial flow blood pump using magnetic fluid shaft seal2022

    • Author(s)
      Okamoto Eiji, Yano Tetsuya, Sekine Kazumitsu, Inoue Yusuke, Shiraishi Yasuyuki, Yambe Tomoyuki, Mitamura Yoshinori
    • Journal Title

      Journal of Artificial Organs

      Volume: 26 Issue: 1 Pages: 12-16

    • DOI

      10.1007/s10047-022-01330-7

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] METHODS FOR INVESTIGATING CONTRACTION CHARACTERISTICS OF A PART OF MUSCLES FOR IMPLANTABLE POWER GENERATION SYSTEMS2022

    • Author(s)
      SAHARA GENTA、HIJIKATA WATARU、INOUE YUSUKE、YAMADA AKIHIRO、SHIRAISHI YASUYUKI、FUKAYA AOI、KARUBE MASATO、GENDA TATSUYA、IWAMOTO NAOKI、TACHIZAKI YUMA、MORITA RYOSUKE、YAMBE TOMOYUKI
    • Journal Title

      Journal of Mechanics in Medicine and Biology

      Volume: 22 Issue: 01 Pages: 2250007-2250007

    • DOI

      10.1142/s0219519422500075

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute Phase Pilot Evaluation of Small Diameter Long iBTA Induced Vascular Graft "Biotube" in a Goat Model2022

    • Author(s)
      Ryuji Higashita , Yasuhide Nakayama, Yasuyuki Shiraishi, Ryosuke Iwai, Yusuke Inoue, Akihiro Yamada , Takesi Terazawa, Tsutomu Tajikawa, Manami Miyazaki, Mamiko Ohara, Tadashi Umeno, Keitaro Okamoto, Tomonori Oie, Tomoyuki Yambe, Shinji Miyamoto
    • Journal Title

      EJVES Vasc Forum

      Volume: 54 Pages: 27-35

    • DOI

      10.1016/j.ejvsvf.2022.01.004

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ローラボンプの繰り返し負荷による流路形状変化が血流特性に及ぼす影響の検討2021

    • Author(s)
      深谷碧, 自石泰之, 山田昭博, 佐原玄太, 井上雄介, 山家智之
    • Journal Title

      ライフサポート

      Volume: 331 Pages: 52-58

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development and accuracy evaluation of a degree of occlusion visualization system for roller pumps used in cardiopulmonary bypass2021

    • Author(s)
      Fukaya A, Shiraishi Y, Inoue Y, Yamada A, Sahara G, Kudo T, Aizawa Y, Yambe T
    • Journal Title

      J Artif Organs

      Volume: 24(1) Issue: 1 Pages: 27-35

    • DOI

      10.1007/s10047-020-01211-x

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel application of indocyanine green fluorescence imaging for real‐time detection of thrombus in a membrane oxygenator2021

    • Author(s)
      Sakurai Hironobu、Fujiwara Tatsuki、Ohuchi Katsuhiro、Hijikata Wataru、Inoue Yusuke、Seki Haruna、Tahara Tomoki、Yokota Sachie、Ogata Asato、Mizuno Tomohiro、Arai Hirokuni
    • Journal Title

      Artificial Organs

      Volume: 45 Issue: 10 Pages: 1173-1182

    • DOI

      10.1111/aor.13999

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hemolysis and von Willebrand factor degradation in mechanical shuttle shear flow tester2021

    • Author(s)
      Shiraishi Y, Tachizaki Y, Inoue Y, Hayakawa M, Yamada A, Kayashima M, Matsumoto M, Horiuchi H, Yambe T
    • Journal Title

      J Artif Organs

      Volume: 24(2) Issue: 2 Pages: 111-119

    • DOI

      10.1007/s10047-020-01219-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preliminary Study of an Objective Evaluation Method for Pulse Diagnosis using Radial Artery Pulse Measurement Device2021

    • Author(s)
      Akihiro Yamada, Yusuke Inoue, Yasuyuki Shiraishi, Takashi Seki, Tomoyuki Yambe
    • Journal Title

      Advanced Biomedical Engineering

      Volume: 10 Issue: 0 Pages: 113-122

    • DOI

      10.14326/abe.10.113

    • NAID

      130008075877

    • ISSN
      2187-5219
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of muscle connection components for implantable power generation system2021

    • Author(s)
      Sahara G, Yamada A, Inoue Y, Shiraishi Y, Hijikata W, Fukaya A, Yambe T
    • Journal Title

      Annu Int Conf IEEE Eng Med Biol Soc.

      Volume: 2021 Pages: 7206-7210

    • DOI

      10.1109/embc46164.2021.9629561

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vitro performance of trans-valve left ventricular assist device installed at aortic valve position2020

    • Author(s)
      Okamoto E, Yano T, Inoue Y, Shiraishi Y, Yambe T, Mitamura Y.
    • Journal Title

      Artif Organs.

      Volume: 44(10) Issue: 10 Pages: 1067-1072

    • DOI

      10.1111/aor.13687

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Optimum Sterilization Methods of Biocompatible Hybrid Material for Artificial Organs2020

    • Author(s)
      Inoue Yusuke、Tashiro Ayaka、Kawase Yukino、Isoyama Takashi、Saito Itsuro、Ono Toshiya、Hara Shintaro、Ishii Kohei、Yurimoto Terumi、Shiraishi Yasuyuki、Yamada Akihiro、Yambe Tomoyuki、Abe Yusuke
    • Journal Title

      Advanced Biomedical Engineering

      Volume: 9 Issue: 0 Pages: 83-92

    • DOI

      10.14326/abe.9.83

    • NAID

      130007843386

    • ISSN
      2187-5219
    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 重症肺炎に対するECMO装着下での経気道的治療法の開発2023

    • Author(s)
      井上雄介、佐藤康史、寺澤武、武輪能明
    • Organizer
      第51回人工心臓と補助循環懇話会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] インペラの円軌道加振による磁気浮上型血液ポンプ内の血栓検出技術の開発2022

    • Author(s)
      畠中 晃平、土方 亘、藤原 立樹、大内 克洋、井上 雄介
    • Organizer
      第60回日本人工臓器学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ECMO装着下における重症肺炎に対する経気道的治療法の開発2022

    • Author(s)
      井上雄介,佐藤康史,寺澤武,堀江風花、山名智尋、武輪能明
    • Organizer
      第60回日本人工臓器学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development of nail type vital sensor for medical device2022

    • Author(s)
      Yusuke Inoue、Tomoyuki Yokota、Kohei Ishii、Akihiro Yamada
    • Organizer
      第4回 COI学術交流会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of nail type vital sensor for medical device2021

    • Author(s)
      Yusuke Inoue, Tomoyuki Yokota, Kohei Ishii, Akihiro Yamada
    • Organizer
      第4回 COI学術交流会
    • Related Report
      2021 Research-status Report
  • [Presentation] 遠心ポンプの血栓検知・予防技術の開発とECMOへの応用2021

    • Author(s)
      土方亘,藤原立樹,大内克洋,井上雄介,丸山修,畠中晃平,田仲結衣,櫻井啓暢
    • Organizer
      日本定常流ポンプ研究会2021
    • Related Report
      2021 Research-status Report
  • [Presentation] 体外循環回路の抗血栓性評価を目的とした急性動物実験モデルの提案2021

    • Author(s)
      櫻井啓暢、藤原立樹、大内克洋、土方亘、井上雄介、丸山修、水野友裕、荒井裕国
    • Organizer
      第59回日本人工臓器学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 旭川医科大学大型慢性動物実験施設における抗血栓ECMOの開発2021

    • Author(s)
      井上雄介、寺澤武、佐藤康史、藤原立樹、大内克洋、土方亘、田仲結衣、畠中晃平、横田幸恵、武輪能明
    • Organizer
      第59回日本人工臓器学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 生体と医療機器の境界面で使用するハイブリッド材料の最適足場検討2021

    • Author(s)
      井上雄介,川瀬由季乃,田代彩夏,斎藤逸郎,磯山隆, 山田 昭博,山家智之,寺澤武,佐藤康史,武輪能明
    • Organizer
      第60回日本生体医工学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 機械循環の高せん断によるフォンウィルブランド因子マルチマー切断に関する研究2020

    • Author(s)
      井上雄介,早川正樹,山田昭博,佐原玄太,白石泰之,佐藤康史,武輪能明,堀内久徳,松本雅則,山家智之
    • Organizer
      第58回日本人工臓器学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 大動脈弁位置埋込式軸流型血液ポンプの拍動性評価と今後の展開2020

    • Author(s)
      岡本英治、矢野哲也、井上雄介、白石泰之、山家智之、三田村好矩
    • Organizer
      代用臓器再生医学研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] 新型ステント開発支援のための大動脈解離血行動態モデル非臨床試験系の構築2020

    • Author(s)
      山田昭博、盛田良介、井上雄介、白石泰之、、佐原玄太、深谷碧、繁浦瑠偉、N.Andrew、Y.Qian、榛沢和彦、山家智之
    • Organizer
      第58回日本人工臓器学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Development of muscle connection parts for implantable power generation system2020

    • Author(s)
      Genta Sahara, Akihiro Yamada, Yusuke Inoue, Yasuyuki Shiraishi, Wataru Hijikata, Aoi Fukaya, Tomoyuki Yambe
    • Organizer
      生体医工学シンポジウム2020
    • Related Report
      2020 Research-status Report
  • [Presentation] How can we determine the optimal cardiopulmonary bypass occlusion?2020

    • Author(s)
      Aoi Fukaya, Yasuyuki Shiraishi, Yusuke Inoue, Akihiko Yamada, Genta Sahara, Takemi Kudo, Yasuhiro Aizawa, Tomoyuki Yambe
    • Organizer
      第154回東北大学加齢医学研究所集談会(154th IDAC Biannual Meeting)
    • Related Report
      2020 Research-status Report
  • [Presentation] 後天性von Willebrand病の血行力学的評価を目的とした流体剪断負荷試験装置の開発2019

    • Author(s)
      舘崎祐馬、福澤奎人、白石泰之、井上雄介、山田昭博、早川正樹、萱島道徳、松本雅則、堀内久徳、山家智之
    • Organizer
      第32回バイオエンジニアリング講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 機械的流体剪断負荷とVWF損傷に関する実験的検討2019

    • Author(s)
      舘崎祐馬、白石泰之、井上雄介、山田昭博、岩元直樹、盛田良介、Ahmad Faiz Ibadurrahman、橋本真登香、早川正樹、萱島道徳、松本雅則、堀内久徳、山家智之
    • Organizer
      第6回加齢医学研究所リトリート
    • Related Report
      2019 Research-status Report
  • [Presentation] ローラによるポンプチューブへの繰返しひずみが圧閉度に及ぼす影響2019

    • Author(s)
      深谷 碧、白石泰之、佐原玄太、井上雄介、山田昭博、工藤剛実、佐々木典子、髙橋るみ、相澤康弘、山家智之
    • Organizer
      第45回日本体外循環技術医学会大会
    • Related Report
      2019 Research-status Report
  • [Book] 循環器疾患 モデル動物の作製と利用 2021 上巻2022

    • Author(s)
      井上雄介ほか
    • Total Pages
      6
    • Publisher
      株式会社エル・アイ・シー
    • ISBN
      9784900487581
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
  • [Patent(Industrial Property Rights)] 磁気浮上型血液ポンプの駆動制御方法、磁気浮上型血液ポンプの駆 動制御 装置及び磁気浮上型血液ポンプシステム2022

    • Inventor(s)
      土方亘,畠中晃平,藤原立樹,大内克洋,井上雄介,武輪能明
    • Industrial Property Rights Holder
      土方亘,畠中晃平,藤原立樹,大内克洋,井上雄介,武輪能明
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-065596
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi