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The development of neuro-mechanical unloading therapy for myocardial infarction

Research Project

Project/Area Number 18K15893
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionNational Cardiovascular Center Research Institute (2019-2020)
Kyushu University (2018)

Principal Investigator

Saku Keita  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 (40567385)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords循環器内科 / 血行動態 / 心筋梗塞 / 心力学 / 左室補助装置 / 自律神経 / 神経刺激 / 虚血性心疾患 / 心不全 / 補助循環 / 医療機器開発
Outline of Final Research Achievements

In the development of neuro-mechanical unloading therapy, we established a control algorithm to regulate both the percutaneous left ventricular assist device and the neurostimulator, after the individual verification in animal experiments. We proved that the addition of bradycardic agent to the percutaneous left ventricular assist device resulted in significant suppression of myocardial oxygen consumption, while improving hemodynamics. We also confirmed that the use of the control algorithm during the acute phase of myocardial infarction enabled stable and marked left ventricular unloading. Finally, we examined the impact of developed system in a canine model of ischemia-reperfusion, and found that the system significantly limited infarct size and worsening of heart failure.

Academic Significance and Societal Importance of the Research Achievements

心筋梗塞治療において、再還流による酸素供給再開に加えて、酸素需要を下げることは梗塞サイズが縮小するが、血行動態を保ちながら心筋酸素消費を抑制する治療法は存在しない。心筋梗塞急性期における左室補助装置と迷走神経刺激を併用した機械-神経最適減負荷アルゴリズムを構築することは、両者の機能、効果を補完することで、血行動態を悪化させることなく、著明な酸素消費低減や心筋保護効果を誘導し、最終的に梗塞サイズの極小化と遠隔期心不全の劇的な予防をもたらす可能性がある。

Report

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

    (45 results)

All 2021 2020 2019 2018 Other

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 16 results,  Open Access: 8 results) Presentation (28 results) (of which Int'l Joint Research: 15 results,  Invited: 7 results) Remarks (1 results)

  • [Journal Article] Aging steepens the slope of power spectrum density of 30-minute continuous blood pressure recording in healthy human subjects2021

    • Author(s)
      Mano Jumpei、Saku Keita、Kinoshita Hiroyuki、Mannoji Hiroshi、Kanaya Shigehiko、Sunagawa Kenji
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 3 Pages: e0248428-e0248428

    • DOI

      10.1371/journal.pone.0248428

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice2020

    • Author(s)
      Deguchi H, Ikeda M, Ide T, Tadokoro T, Ikeda S, Okabe K, Ishikita A, Saku K, Matsushima S, Tsutsui H.
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 6 Pages: 1028-1033

    • DOI

      10.1253/circj.CJ-19-1039

    • NAID

      130007846233

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2020-05-25
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of haemodynamics after interatrial shunt for heart failure using the generalized circulatory equilibrium2020

    • Author(s)
      Nishikawa Takuya、Saku Keita、Uike Kiyoshi、Uemura Kazunori、Sunagawa Genya、Tohyama Takeshi、Yoshida Keimei、Kishi Takuya、Sunagawa Kenji、Tsutsui Hiroyuki
    • Journal Title

      ESC Heart Failure

      Volume: 7 Issue: 5 Pages: 3075-3085

    • DOI

      10.1002/ehf2.12935

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of hemodynamics after atrial septal defect closure using a framework of circulatory equilibrium in dogs2020

    • Author(s)
      Uike Kiyoshi
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 319 Issue: 5 Pages: 938-947

    • DOI

      10.1152/ajpheart.00098.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Partial Support of the Left Ventricular Assist Device Shifts the Systemic Cardiac Output Curve Upward in Proportion to the Effective Left Ventricular Ejection Fraction in Pressure-Volume Loop2020

    • Author(s)
      Kakino Takamori、Saku Keita、Nishikawa Takuya、Sunagawa Kenji
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 7

    • DOI

      10.3389/fcvm.2020.00163

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Smart Baroreceptor Activation Therapy Strikingly Attenuates Blood Pressure Variability in Hypertensive Rats With Impaired Baroreceptor.2020

    • Author(s)
      Tohyama T, Hosokawa K, Saku K, Oga Y, Tsutsui H, Sunagawa K.
    • Journal Title

      Hypertension.

      Volume: 75 Issue: 3 Pages: 885-892

    • DOI

      10.1161/hypertensionaha.119.13673

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension.2019

    • Author(s)
      Shinoda M, Saku K, Oga Y, Tohyama T, Nishikawa T, Abe K, Yoshida K, Kuwabara Y, Fujii K, Ishikawa T, Kishi T, Sunagawa K, Tsutsui H.
    • Journal Title

      Exp Physiol

      Volume: 104 Issue: 8 Pages: 1164-1178

    • DOI

      10.1113/ep087253

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechano-chronotropic Unloading During the Acute Phase of Myocardial Infarction Markedly Reduces Infarct Size via the Suppression of Myocardial Oxygen Consumption.2019

    • Author(s)
      Sunagawa G, Saku K, Arimura T, Nishikawa T, Mannoji H, Kamada K, Abe K, Kishi T, Tsutsui H, Sunagawa K.
    • Journal Title

      J Cardiovasc Transl Res.

      Volume: 12 Issue: 2 Pages: 124-134

    • DOI

      10.1007/s12265-018-9809-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Estimation of the baroreflex total loop gain by the power spectral analysis of continuous arterial pressure recordings.2019

    • Author(s)
      Mannoji H, Saku K, Nishikawa T, Tohyama T, Kamada K, Abe K, Sunagawa G, Kishi T, Sunagawa K, Tsutsui H.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 316 Issue: 4 Pages: H828-H839

    • DOI

      10.1152/ajpheart.00681.2018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Thoracic endografting increases cardiac afterload and leads to left ventricular hypertrophy in dogs.2019

    • Author(s)
      Yamashita Y, Oishi Y, Motomatsu Y, Hirayama K, Harada T, Ushijima T, Fujita S, Kimura S, Sonoda H, Tatewaki H, Tanoue Y, Sunagawa G, Nishikawa T, Saku K, Shiose A.
    • Journal Title

      Eur J Cardiothorac Surg.

      Volume: 55 Issue: 4 Pages: 618-625

    • DOI

      10.1093/ejcts/ezy402

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc.2019

    • Author(s)
      Kamada K, Saku K, Tohyama T, Kawada T, Mannoji H, Abe K, Nishikawa T, Sunagawa G, Kishi T, Sunagawa K, Tsutsui H.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 316 Issue: 1 Pages: H35-H44

    • DOI

      10.1152/ajpheart.00515.2018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of TLR9-NF-kB-Mediated Sterile Inflammation Improves Pressure Overload;Induced Right Ventricular Dysfunction in Rats.2018

    • Author(s)
      Yoshida K, Abe K, Tanaka M, Saku K, Shinoda-Sakamoto M, Ishikawa T, Watanabe T, Oka M, Sunagawa K, Tsutsui H.
    • Journal Title

      Cardiovasc Res.

      Volume: 115 Issue: 3 Pages: 658-668

    • DOI

      10.1093/cvr/cvy209

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The impact of volume loading-induced low pressure baroreflex activation on arterial baroreflex-controlled sympathetic arterial pressure regulation in normal rats2018

    • Author(s)
      Oga Yasuhiro、Saku Keita、Nishikawa Takuya、Kishi Takuya、Tobushi Tomoyuki、Hosokawa Kazuya、Tohyama Takeshi、Sakamoto Takafumi、Sunagawa Kenji、Tsutsui Hiroyuki
    • Journal Title

      Physiological Reports

      Volume: 6 Issue: 19 Pages: e13887-e13887

    • DOI

      10.14814/phy2.13887

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Electrical Vagal Nerve Stimulation Ameliorates Pulmonary Vascular Remodeling and Improves Survival in Rats With Severe Pulmonary Arterial Hypertension.2018

    • Author(s)
      Yoshida K, Saku K, Kamada K, Abe K, Tanaka-Ishikawa M, Tohyama T, Nishikawa T, Kishi T, Sunagawa K, Tsutsui H.
    • Journal Title

      JACC Basic Transl Sci.

      Volume: 12 Issue: 5 Pages: 657-671

    • DOI

      10.1016/j.jacbts.2018.07.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulmonary arterial input impedance reflects the mechanical properties of pulmonary arterial remodeling in rats with pulmonary hypertension.2018

    • Author(s)
      Nishikawa T., Saku K., Kishi T., Tohyama T., Abe K, Oga Y., Arimura T., Sakamoto T., Yoshida K., Sunagawa K., Tsutsui H.
    • Journal Title

      Life Sci.

      Volume: 21 Pages: 225-232

    • DOI

      10.1016/j.lfs.2018.10.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Derangement of open-loop static and dynamic characteristics of the carotid sinus baroreflex in streptozotocin-induced type 1 diabetic rats.2018

    • Author(s)
      Kawada T, Shimizu S, Hayama Y, Yamamoto H, Saku K, Shishido T, Sugimachi M.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol.

      Volume: 315 Issue: 3 Pages: R553-R567

    • DOI

      10.1152/ajpregu.00092.2018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 循環動態視点で再考する最適な補助循環活用ストラテジー2020

    • Author(s)
      朔 啓太
    • Organizer
      日本心不全学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Development of Smart Baroreflex Activation Therapy Targeting Blood Pressure Variability2020

    • Author(s)
      Keita Saku
    • Organizer
      Hypertension Seoul
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PVAに着目した心筋梗塞治療2020

    • Author(s)
      朔 啓太
    • Organizer
      日本循環制御医学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 自律神経制御による循環器疾患治療デバイス  ―病態生理からみた現状分析と課題―2020

    • Author(s)
      朔 啓太
    • Organizer
      日本自律神経学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Upward-shift of cardiac output curve determined by the synergistic effect of support flow and left ventricular ejection fraction is the fundamental mechanism to improve hemodynamics by left ventricular assist device2019

    • Author(s)
      Keita Saku, Takamori Kakino, Kenji Sunagawa
    • Organizer
      Acure meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The short-term Neuro-Mechanical Unloading therapy prior to reperfusion strikingly reduces the infarct size and prevents subsequent heart failure in a dog model of ischemia-reperfusion2019

    • Author(s)
      Keita Saku
    • Organizer
      The 63rd Annual Scientific Meeting of The Korean Society of Cardiology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ACSチームの底力を上げる!循環動態フレームワークで考えるImpellaの最適活用法2019

    • Author(s)
      朔 啓太
    • Organizer
      第42回日本心血管インターベンション治療学会東海北陸地方会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 日本発!ニューロモデュレーションデバイスによる心不全治療への挑戦2019

    • Author(s)
      朔 啓太
    • Organizer
      第23回日本心不全学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Impella for Heart Recovery2019

    • Author(s)
      朔 啓太
    • Organizer
      第23回日本心不全学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 症例から学ぶインペラによる救命/心保護ストラテジー~実臨床の役に立つ血行動態学入門~2019

    • Author(s)
      朔啓太
    • Organizer
      第251回日本循環器学会 関東甲信越地方会・教育セッション
    • Related Report
      2018 Research-status Report
  • [Presentation] Impella時代の循環器診療を乗り切るための臨床血行動態学入門2019

    • Author(s)
      朔啓太
    • Organizer
      第48回日本心血管インターベンション治療学会北海道地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] Simulated Microgravity Exposure Strikingly Attenuates the Baroreflex Total Loop Gain and Induces Orthostatic Hypotension.2018

    • Author(s)
      Kamada K, Saku K, Mannoji H, Tohyama T, Nishikawa T, Sunagawa G, Abe K, Kishi T, Sunagawa K.
    • Organizer
      40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Reperfusion Therapy with Delayed Vagal Nerve Stimulation in Acute Myocardioal Infraction Stringly Reduces Infract Size and Improves Left Ventricular Function in The Long-term.2018

    • Author(s)
      Sunagawa G, Saku H, Arimura T, Akashi T, Kishi T, Tsutsui H, Sunagawa K.
    • Organizer
      40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The presence of baroreflex failure augments the variability of left atrial pressure and triggers acute pulmonary edema in a rat with chronic heart failure2018

    • Author(s)
      Abe K, Saku K, Mannoji H, Sunagawa G, Kamada K, Kishi T, Hoka S, Sunagawa K, Tsutsui H.
    • Organizer
      European Society of Cardiology Cngress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Vagal nerve stimulation restores autonomic balance, super-normalizes right ventricular function and prevents the worsening of right heart failure in chronic pulmonary arterial banding model rats2018

    • Author(s)
      Yoshida K, Saku K, Sunagawa K.
    • Organizer
      European Society of Cardiology Cngress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Unresponsiveness of baroreflex sympathetic regulation leads to orthostatic intolerance in a rat model of type 2 diabetes mellitus.2018

    • Author(s)
      Kamada K, Saku K, Tsutsui H, Sunagawa K.
    • Organizer
      American Autonomic Society 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Smart Impella unloading in the acute phase of MI markedly reduces infarct size and prevents LV dysfunction in the long term2018

    • Author(s)
      Kamada K, Saku K, Sunagawa G, Nishikawa T, Sunagawa K.
    • Organizer
      The A-CURE Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Impella combined with veno-arterial extracorporeal membrane oxygenation effectively unloads the left ventricle with improving hemodynamics in a dog model of cardiogenic shock2018

    • Author(s)
      Sunagawa G, Saku K, Nishikawa T, Akashi T, Kishi T, Tsutsui H, Sunagawa K.
    • Organizer
      The A-CURE Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Diabetes Mellitus Markedly Attenuates the Baroreflex-mediated Heart Rate Response and Makes the Histogram of Heart Rate Distribution Bimodal2018

    • Author(s)
      Kamada K, Saku K, Tohyama T, Kishi T, Nishokawa T, Mannoji H, Sunagawa G, Abe K, Sunagawa K, Tsutsui H
    • Organizer
      Scientific Sessions 2018 of the American Heart Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Diabetes Mellitus Markedly Deteriorates Baroreflex Regulation of Sympathetic Nerve Activity in the Physiological Arterial Pressure Range and Exacerbates Orthostatic Intolerance.2018

    • Author(s)
      Kamada K, Saku K, Tohyama T, Kishi T, Nishokawa T, Mannoji H, Sunagawa G, Abe K, Sunagawa K, Tsutsui H.
    • Organizer
      Scientific Sessions 2018 of the American Heart Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Reperfusion therapy with delayed vagal nerve stimulation in acute myocardial infarction strikingly reduces infarct size and improves left ventricular function.2018

    • Author(s)
      Sunagawa G, Saku K, Arimura T, Akashi T, Kishi T, Tsutsui H, Sunagawa K
    • Organizer
      Scientific Sessions 2018 of the American Heart Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Combination of mechanical unloading (Impella) and chronotropic unloading is more powerful than mechanical unloading alone in reducing infarct size and preventing chronic heart failure2018

    • Author(s)
      Sunagawa G, Saku K, Akashi T, Kishi T, Tsutsui H, Sunagawa K.
    • Organizer
      Scientific Sessions 2018 of the American Heart Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ECPELLA unloading in acute myocardial infarction reduces infarct size via powerful reduction of Left Ventricular pressure volume area.2018

    • Author(s)
      Sunagawa G, Saku K, Nishikawa T, Akashi T, KIshi T, Tsutsui H, Sunagawa K.
    • Organizer
      Scientific Sessions 2018 of the American Heart Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 動脈圧反射機能不全は慢性心不全ラットにおいて著名な左房圧変動を誘発し、肺水腫リスクを増加させる2018

    • Author(s)
      阿部潔和、朔啓太、萬納寺洋士、鎌田和宏、砂川玄哉、岸拓弥、外須美夫、砂川賢二、筒井裕之
    • Organizer
      第39回日本循環制御医学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 模擬微少重力は動脈圧反射の動作点ゲインを著減させることで起立不耐性を誘発する2018

    • Author(s)
      鎌田和宏、朔啓太、萬納寺洋士、岸拓弥、遠山岳詩、西川拓也、吉田賢明、阿部潔和、砂川賢二、筒井裕之
    • Organizer
      第57回日本生体医工学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 循環平衡理論による心房間シャントの血行動態予測2018

    • Author(s)
      西川拓也、朔啓太、鵜池清、砂川玄哉、遠山岳詩、岸拓弥、上村和紀、砂川賢二、筒井裕之
    • Organizer
      第57回日本生体医工学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 植え込み型自律神経刺激装置による革新的肺高血圧症治療法の開2018

    • Author(s)
      朔啓太
    • Organizer
      第3回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 迷走神経刺激による革新的肺高血圧症治療法の開発2018

    • Author(s)
      吉田賢明、朔啓太、鎌田和宏、阿部弘太郎、石川真理子、遠山岳詩、西川拓也、岸拓弥、砂川賢二、筒井裕之
    • Organizer
      第3回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2018 Research-status Report
  • [Remarks] iVNS(経皮的迷走神経刺激)の紹介サイト

    • URL

      https://ivns.circ-dynamics.jp/

    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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