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Pathogenesis in the mature myocardium following selective manipulation of the innervation of the heart in the larval stage

Research Project

Project/Area Number 18K16408
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55030:Cardiovascular surgery-related
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Yohsuke Hayama  国立研究開発法人国立循環器病研究センター, 研究所, 客員研究員 (50802964)

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: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords交感神経 / 副交感神経 / リモデリング / 血管内皮 / 炎症 / 線維化 / マクロファージ / 細胞外分泌小胞 / 細胞増殖 / 拡張障害 / 自律神経 / 心臓支配神経 / 心筋障害 / 心筋成長 / 成人先天性心疾患
Outline of Final Research Achievements

In this study, we analyzed the effects of injury and regeneration of the nerves, mainly in myocardial tissue, on recovery and regeneration from tissue injury, mainly using genetic methods. In myocardial tissue, the sympathetic nerves that increase during regeneration after injury may induce fibrosis, mainly on the epicardial side and around blood vessels, which may be part of the pathology that causes problems in clinical practice. Other observations suggested a linkage between the nervous system, vascular endothelial cells, and inflammatory cells, but the phenomena were not consistent from organ to organ, suggesting that inflammatory cells play a leading role in tissue regeneration.

Academic Significance and Societal Importance of the Research Achievements

交感神経が心不全の病態形成に重要な役割を果たしていることは良く知られているが、同病理が神経トーンの変化する例えば心臓周術期にも強く関係しており、神経の再支配が組織学的な直接のリモデリング及ぼすことが再確認された。また侵襲に対する応答には炎症細胞の関与が重要と考えられ、治療介入を考える上で示唆を与える。いずれも例えば小児心臓手術において周術期管理の重要性を説くものであり、社会的に意義があると考える。

Report

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

    (26 results)

All 2020 2019 2018

All Journal Article (19 results) (of which Peer Reviewed: 19 results,  Open Access: 1 results) Presentation (7 results)

  • [Journal Article] Septal Flash-like Motion of the Earlier Activated Ventricular Wall Represents the Pathophysiology of Mechanical Dyssynchrony in Single-Ventricle Anatomy2020

    • Author(s)
      Hayama Yohsuke、Miyazaki Aya、Ohuchi Hideo、Miike Hikari、Negishi Jun、Sakaguchi Heima、Kurosaki Kenichi、Shimizu Shuji、Kawada Toru、Sugimachi Masaru
    • Journal Title

      Journal of the American Society of Echocardiography

      Volume: 33 Issue: 5 Pages: 612-621.e2

    • DOI

      10.1016/j.echo.2019.11.016

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Progressive stiffening and relatively slow growth of the dilated ascending aorta in long-term Fontan survivors―Serial assessment for 15 years2020

    • Author(s)
      Hayama Yohsuke、Ohuchi Hideo、Negishi Jun、Iwasa Toru、Sakaguchi Heima、Miyazaki Aya、Tsuda Etsuko、Kurosaki Kenichi
    • Journal Title

      International Journal of Cardiology

      Volume: 316 Pages: 87-93

    • DOI

      10.1016/j.ijcard.2020.04.071

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Stiffened and Dilated Ascending Aorta on Aerobic Exercise Capacity in Repaired Patients With Complex Congenital Heart Disease2020

    • Author(s)
      Hayama Yohsuke、Ohuchi Hideo、Negishi Jun、Iwasa Toru、Sakaguchi Heima、Miyazaki Aya、Tsuda Etsuko、Kurosaki Kenichi
    • Journal Title

      The American Journal of Cardiology

      Volume: 129 Pages: 87-94

    • DOI

      10.1016/j.amjcard.2020.05.028

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of delayed ventricular wall area ratio on pathophysiology of mechanical dyssynchrony: implication from single-ventricle physiology and 0D modeling2020

    • Author(s)
      Hayama Yohsuke、Shimizu Shuji、Kawada Toru、Negishi Jun、Sakaguchi Heima、Miyazaki Aya、Ohuchi Hideo、Yamada Osamu、Kurosaki Kenichi、Sugimachi Masaru
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 70 Issue: 1 Pages: 38-38

    • DOI

      10.1186/s12576-020-00765-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Open-loop analysis on sympathetically mediated arterial pressure and urine output responses in rats: effect of renal denervation2020

    • Author(s)
      Kawada Toru、Hayama Yohsuke、Nishikawa Takuya、Suehara Satoru、Sawada Satoshi、Tanaka Tetsuo、Uenohara Minako、Sugimachi Masaru
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 70 Issue: 1 Pages: 32-32

    • DOI

      10.1186/s12576-020-00759-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Even weak vasoconstriction from rilmenidine can be unmasked in vivo by opening the baroreflex feedback loop.2019

    • Author(s)
      Kawada T, Hayama Y, Nishikawa T, Yamamoto H, Tanaka K, Sugimachi M.
    • Journal Title

      Life Sciences

      Volume: 219 Pages: 144-51

    • DOI

      10.1016/j.lfs.2019.01.009

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Abnormal glucose metabolism in patients with Fontan circulation: Unique characteristics and associations with Fontan pathophysiology2019

    • Author(s)
      Hideo Ohuchi, Jun Negishi, Yohsuke Hayama, Hikari Miike, Dai Suzuki, Kimiko Nakajima, Nao Konagai, Toru Iwasa, Heima Sakaguchi, Kenichi Kurosaki, Michikazu Nakai
    • Journal Title

      American Heart Journal

      Volume: 216 Pages: 125-135

    • DOI

      10.1016/j.ahj.2019.07.013

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ivabradine preserves dynamic sympathetic control of heart rate despite inducing significant bradycardia in rats.2019

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

      The journal of physiological sciences

      Volume: 69 Issue: 2 Pages: 211-22

    • DOI

      10.1007/s12576-018-0636-2

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Accentuated antagonism of vagal heart rate control and less potent prejunctional inhibition of vagal acetylcholine release during sympathetic nerve stimulation in the rat.2019

    • Author(s)
      Kawada T, Sonobe T, Hayama Y, Nishikawa T, Miyamoto T, Akiyama T, Pearson JT, Sugimachi M
    • Journal Title

      Autonomic neuroscience : basic & clinical

      Volume: 218 Pages: 25-30

    • DOI

      10.1016/j.autneu.2019.02.005

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluating the response to cardiac resynchronization therapy performed with a new ventricular morphology-based strategy for congenital heart disease.2019

    • Author(s)
      Aya Miyazaki, Jun Negishi, Yosuke Hayama, Shigehito Baba, Yu Matsumura, Yuriko Shima, Etusko Tsuda, Heima Sakaguchi, Takaya Hoashi, Koji Kagisaki, Takashi Noda, Hiraku Doi, Hajime Ichikawa, Hideo Ohuchi
    • Journal Title

      Heart and Vessels

      Volume: 34 Issue: 8 Pages: 1340-1350

    • DOI

      10.1007/s00380-019-01369-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mild hypothermia is ineffective to protect against myocardial injury induced by chemical anoxia or forced calcium overload.2019

    • Author(s)
      Kawada T, Yamazaki T, Akiyama T, Hayama Y, Sugimachi M
    • Journal Title

      Journal of Cardiovascular Pharmacology

      Volume: 73 Issue: 2 Pages: 100-104

    • DOI

      10.1097/fjc.0000000000000639

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute effects of intravenous carvedilol versus metoprolol on baroreflex-mediated sympathetic circulatory regulation in rats2019

    • Author(s)
      Yamamoto Hiromi、Kawada Toru、Shimizu Shuji、Hayama Yohsuke、Shishido Toshiaki、Iwanaga Yoshitaka、Fukuda Kanji、Miyazaki Shunichi、Sugimachi Masaru
    • Journal Title

      International Journal of Cardiology

      Volume: 285 Pages: 65-71

    • DOI

      10.1016/j.ijcard.2019.02.062

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression2019

    • Author(s)
      Kamiya Atsunori、Hayama Yohsuke、Kato Shigeki、Shimomura Akihiko、Shimomura Takushi、Irie Katsumasa、Kaneko Ryosuke、Yanagawa Yuchio、Kobayashi Kazuto、Ochiya Takahiro
    • Journal Title

      Nature Neuroscience

      Volume: 22 Issue: 8 Pages: 1289-1305

    • DOI

      10.1038/s41593-019-0430-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intravenous ivabradine augments the dynamic heart rate response to moderate vagal nerve stimulation in anesthetized rats.2019

    • Author(s)
      Kawada T, Yamamoto H, Uemura K, Hayama Y, Nishikawa T, Sugimachi M.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 317 Issue: 3 Pages: H597-H606

    • DOI

      10.1152/ajpheart.00288.2019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Contrasting open-loop dynamic characteristics of sympathetic and vagal systems during baroreflex-mediated heart rate control in rats.2019

    • Author(s)
      Toru Kawada, Hiromi Yamamoto, Yohsuke Hayama, Takuya Nishikawa, Kunihiko Tanaka, Masaru Sugimachi.
    • Journal Title

      American Journal of Physiology. Regulatory, Integratory and Comparative Physiology

      Volume: 317 Issue: 6 Pages: R879-R890

    • DOI

      10.1152/ajpregu.00231.2019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Central activation of cardiac vagal nerve by α2-adrenergic stimulation is impaired in streptozotocin-induced type 1 diabetic rats.2019

    • Author(s)
      Kawada T, Akiyama T, Sonobe T, Shimizu S, Hayama Y, Pearson JT, Shishido T, Sugimachi M
    • Journal Title

      Autonomic Neuroscience

      Volume: 219 Pages: 39-45

    • DOI

      10.1016/j.autneu.2018.09.001

    • 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
  • [Journal Article] Lumped parameter model for hemodynamic simulation of congenital heart diseases.2018

    • Author(s)
      Shimizu S, Une D, Kawada T, Hayama Y, Kamiya A, Shishido T, Sugimachi M
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 68 Issue: 2 Pages: 103-11

    • DOI

      10.1007/s12576-017-0585-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stenotic Lesions and the Maximum Diameter of Coronary Artery Aneurysms in Kawasaki Disease.2018

    • Author(s)
      Tsuda E, Tsujii N, Hayama Y.
    • Journal Title

      The Journal of Pediatrics

      Volume: 194 Pages: 165-70

    • DOI

      10.1016/j.jpeds.2017.09.077

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Rebound Stretch Motion of the Earlier Activated Wall Represents the Pathophysiology of Mechanical Dyssynchrony in Single- Ventricle Anatomy2020

    • Author(s)
      羽山 陽介, 清水 秀二, 川田 徹, 三池 虹, 坂口 平馬, 宮﨑 文, 大内 秀雄, 黒嵜 健一, 杉町 勝
    • Organizer
      第56回日本小児循環器学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Ventricular Morphology as Well as Conduction Delay Plays a Key Role in the Pathogenesis of Mechanical Dyssynchrony of Univentricular Heart2019

    • Author(s)
      Yohsuke Hayama, Shuji Shimizu, Toru Kawada, Masaru Sugimachi
    • Organizer
      第83回日本循環器学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Theoretical Analysis in the Pathogenesis of Mechanical Dyssynchrony in the Univentricular Heart2019

    • Author(s)
      Hayama Y, Shimizu S, Kawata T, Sugimachi M.
    • Organizer
      The 57th Annual Meeting of the Japanese Society for Medical and Biological Engineering
    • Related Report
      2018 Research-status Report
  • [Presentation] High Plasma Levels of Presepsin, a Marker of Bacterial Infection, Reflect Global Fontan Pathophysiology.2018

    • Author(s)
      Toyoshima Y, Ohuchi H, Hayama Y, Fujino M, Fukuyama M, Negishi J, Iwasa T, Kurosaki K
    • Organizer
      American Heart Association's Scientific Sessions 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Preceding Contraction of Less Distensible Ventricular Compartment Plays a Key Role in the Pathogenesis of Mechanical Dyssynchrony in the Univentricular Heart2018

    • Author(s)
      Hayama Y, Shimizu S, Kawata T, Sugimachi M.
    • Organizer
      American Heart Association's Scientific Sessions 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Ventricular Morphology as Well as Conduction Delay Plays a Key Role in the Pathogenesis of Mechanical Dyssynchrony of Univentricular Heart2018

    • Author(s)
      Hayama Y, Shimizu S, Kawata T, Sugimachi M.
    • Organizer
      The 83rd Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2018 Research-status Report
  • [Presentation] 心室域による拡張能の差がFontan術後単心室における機械的非同期の病態形成に重要である - シミュレーションによる考察2018

    • Author(s)
      羽山 陽介, 清水 秀二, 川田 徹, 杉町 勝
    • Organizer
      The 45th Annual Meeting of Japanese Society of Pediatric Cardiology and Cardiac Surgery
    • Related Report
      2018 Research-status Report

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

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