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Fundamental study on developing heart failure treatment targeting the central nervous system.

Research Project

Project/Area Number 23650213
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurophysiology and muscle physiology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

SIRAI Mikiyasu  独立行政法人国立循環器病研究センター, 研究所, 部長 (70162758)

Co-Investigator(Kenkyū-buntansha) AKIYAMA Tsuyoshi  独立行政法人国立循環器病研究センター, 研究所, 室長 (70202554)
TSUCHIMOCHI Hirotsugu  独立行政法人国立循環器病研究センター, 研究所, 室長 (60379948)
Co-Investigator(Renkei-kenkyūsha) TO Seikon  独立行政法人国立循環器病研究センター, 研究所, 非常勤研究員 (90590646)
MORIMOTO Satio  九州大学, 医学研究科, 助教授 (50202362)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords心不全 / 心筋梗塞 / 拡張型心筋症 / 心臓自律神経活動 / 心臓マイクロダイアリシス / 心拍変動 / グレリン / 慢性心不全 / 不整脈 / 心臓リモデリング / 冠循環 / 橋渡し研究
Research Abstract

Cardiac parasympathetic activity, which has a cardioprotective effect, was assessed in a mouse model of dilated cardiomyopathy (DCM) using a microdialysis technique. We found that the adrenergic mechanism for controlling cardiac parasympathetic activity was suppressed at the central nervous system level. Percutaneous ghrelin injection for one month augmented cardiac parasympathetic activity and attenuated sympathetic activity and then improved myocardial remodeling and contractility, reducing the high mortality rate associated with DCM. One dose of ghrelin prevented the acute and sustained increase in cardiac sympathetic tone after myocardial infarction and then reduced the high mortality rate attributable to sudden heart failure in the rat.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (46 results)

All 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (28 results) (of which Invited: 1 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Synchrotro radiation imaging for advancing our understanding of ardiovascular function2013

    • Author(s)
      Mikiyasu Shirai, Daryl O. Schwenke, Hirotsugu Tsuchimochi, Keiji Umetani, Naoto Yagi, James T. Pearson
    • Journal Title

      Circ Res

      Volume: 112(1) Issue: 1 Pages: 209-221

    • DOI

      10.1161/circresaha.111.300096

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Myosin heads are displaced from actin filaments in the in situ beating rat heart in early diabetes.2013

    • Author(s)
      Jenkins MJ, Pearson JT, Schwenke DO, Edgley AJ, Sonobe T, Fujii Y, Ishibashi-Ueda H, Kelly DJ, Yagi N, Shirai M.
    • Journal Title

      Biophys J.

      Volume: 104 Issue: 5 Pages: 1065-1072

    • DOI

      10.1016/j.bpj.2013.01.037

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired pulmonary blood flow distribution in congestive heart failure assessed using synchrotron radiation microangiography.2013

    • Author(s)
      Shirai M, Beard M, Pearson JT, Son obe T, Tsuchimochi H, Fujii Y, Gray E, Umetani K. Schwenke DO.
    • Journal Title

      J Synchrotron Radiat

      Volume: 20(3) Issue: 3 Pages: 441-448

    • DOI

      10.1107/s0909049513007413

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo monitoring of acetylcholine release from cardiac vagal nerve endings in anaesthetized mice.2013

    • Author(s)
      Zhan DY, Du CK, Akiyama T, Sonobe T, Tsuchimochi H, Shirai M.
    • Journal Title

      Auton Neurosci

      Volume: 176(1-2) Issue: 1-2 Pages: 91-94

    • DOI

      10.1016/j.autneu.2013.02.014

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of serotonin uptake and degradation to myocardial interstitial seroton in levels during ischaemia-reperfusion in rabbits.2013

    • Author(s)
      Sonobe T, Akiyama T, Du CK, Zhan DY, Shirai M.
    • Journal Title

      Acta Physiol (Oxf).

      Volume: 207 Issue: 2 Pages: 260-268

    • DOI

      10.1111/j.1748-1716.2012.02461.x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic synchrotron imaging of diabetic rat coronary microcirculation in vivo2012

    • Author(s)
      Jenkins MJ, Edgley AJ, Sonobe T, Umetani K, Schwenke DO, Fujii Y, Brown RD, Kelly DJ, Shirai M, Pearson JT
    • Journal Title

      Arterioscler Thromb Vase Biol

      Volume: 32 Issue: 2 Pages: 370-377

    • DOI

      10.1161/atvbaha.111.237172

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] One dose of ghrelin prevents the acute and sustained increase in cardiac sympathetic tone after myocardial infarction2012

    • Author(s)
      Schwenke DO, Tokudome T, Kishimoto I, Horio T, Cragg PA, Shirai M, Kangawa K
    • Journal Title

      Endocrinology

      Volume: 153(5) Issue: 5 Pages: 2436-2443

    • DOI

      10.1210/en.2011-2057

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Medetomidine, an α2-adrenergic agonist, activates cardiac vagal nerve through modulation of baroreflex control.2012

    • Author(s)
      Shimizu S, Akiyama T, Kawada T, Sata Y, Mizuno M, Kamiya A, Shishido T, Inagaki M, Shirai M, Sano S, Sugimachi M.
    • Journal Title

      Circ. J.

      Volume: 76 Pages: 152-159

    • NAID

      10030034497

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Central vagal activation by alpha2-adrenergic stimulation is impaired in spontaneously hypertensive rats2012

    • Author(s)
      Kawada T, Akiyama T, Shimizu S, Kamiya A, Uemura K, et al
    • Journal Title

      Acta Physiol (Oxf)

      Volume: (in press) Issue: 1 Pages: 72-79

    • DOI

      10.1111/j.1748-1716.2012.02439.x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Medetomidine, an α2-adrenergic agonist, activates cardiac vagal nerve through modulation of baroreflex control2012

    • Author(s)
      Shimizu S, Akiyama T, Kawada T, Sata Y, Mizuno M, Kamiya A, Shishido T, Inagaki M, Shirai M, Sano S, Sugimachi M
    • Journal Title

      Circ J

      Volume: 76 Pages: 152-159

    • NAID

      10030034497

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of rho kinase signaling and endothelial dysfunction in modulating blood flow distribution in pulmonary hypertension2011

    • Author(s)
      Daryl Schwenke, James Pearson, Takashi Sonobe, Hatsue Ishibashi-Ueda, Akito Shimouchi, Kenji Kangawa, Keiji Umetani, Mikiyasu Shirai
    • Journal Title

      J Appl Physiol

      Volume: 110 Issue: 4 Pages: 901-908

    • DOI

      10.1152/japplphysiol.01318.2010

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Imaging of the closed-chest mouse pulmonary circulation using synchrotron radiation microangiography2011

    • Author(s)
      Sonobe T, Schwenke DO, Pearson JT, Yoshimoto M, Fujii Y, Umetani K, Shirai M
    • Journal Title

      J Appl Physiol

      Volume: 111 Issue: 1 Pages: 75-80

    • DOI

      10.1152/japplphysiol.00205.2011

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exogenous ghrelin improves blood flow distribution in pulmonary hypertension-assessed using synchrotron radiation microangiography2011

    • Author(s)
      Schwenke DO, Gray EA, Pearson JT, Sonobe T, Ishibashi-Ueda H, Campillo I, Kangawa K, Umetani K, Shirai M
    • Journal Title

      Pflugers Arch

      Volume: 462 Issue: 3 Pages: 397-406

    • DOI

      10.1007/s00424-011-0992-8

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gab1 is essential for postnatal angiogenesis via hepatocyte growth factor/c-Met signaling2011

    • Author(s)
      Shioyama W, Nakaoka Y, Higuchi K, Minami T, Taniyama Y, Nishida K, Kidoya H, Sonobe T, Naito H, Arita Y, Hashimoto T, Kuroda T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I
    • Journal Title

      Circ Res

      Volume: 108 Issue: 6 Pages: 664-675

    • DOI

      10.1161/circresaha.110.232223

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Centrally administered ghrelin activates cardiac vasal nerve in anesthetized rabbits2011

    • Author(s)
      Shimizu S, Akiyama T, Kawada T, Sonobe T, Kamiya A, Shishido T, Tokudome T, Hosoda H, Shirai M, Kangawa K, Sugimachi M
    • Journal Title

      Auton Neurosci

      Volume: 162 Issue: 1-2 Pages: 60-65

    • DOI

      10.1016/j.autneu.2011.04.001

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 視床下部歩行誘発野の刺激は麻酔下ラットの心筋組織血流量を増加させる2013

    • Author(s)
      土持裕胤、曽野部崇、稲垣薫克、白井幹康
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] モノクロタリン肺高血圧症ラットにおける呼気水素と一酸化炭素生成の相互関連2013

    • Author(s)
      水上智恵、下内章人、野瀬和利、谷口健太郎、白井幹康
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 腎血管性高血圧ラットモデルでの高血圧発症初期における動脈圧と交感神経活動の変化2013

    • Author(s)
      吉本光佐、秋山剛、曽野部崇、藤井豊、三木健寿、白井幹康
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 初期糖尿病ラットの拍動心臓で検出されたクロスブリッジ形成・解離の異常2013

    • Author(s)
      白井幹康、ジェンキンス・マシュー、曽野部崇、藤井豊、土持裕胤、吉本光佐、稲垣薫克、八木直人
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 慢性低酸素により生じる右心室肥大におけるNCS-1の働き2013

    • Author(s)
      稲垣薫克、土持裕胤、西谷友重、若林繁夫、白井幹康
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] マウス心臓交感神経終末におけるノルエピネフリン動態の解析-マイクロダイアリシス法を用いて-2013

    • Author(s)
      戦冬雲、杜成坤、秋山剛、曽野部崇、白井幹康
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] α2Aアドレナリン受容体作動薬であるグアンファシンは、過度の交感神経抑制なしに心臓迷走神経活動を亢進する2013

    • Author(s)
      清水秀二、川田徹、秋山剛、神谷厚範、白井幹康、杉町勝
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 高血圧自然発症ラットにおける交感神経活動と動脈圧の長期連続計測とその因果関係2013

    • Author(s)
      峯山直子、吉本光佐、粟津裕子、大西佑美、島津明佳、白井幹康、三木健寿
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 人工心肺中の高酸素吸送は生体の炎症反応を助長する2013

    • Author(s)
      藤井豊、白井幹康、武輪能明、巽英介、妙中義之
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 拡張型心筋症ノックインマウスに対するグレリンの治療効果2013

    • Author(s)
      杜成坤、戦冬雲、森本幸生、秋山剛、寒川賢治、白井幹康
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] Early diabetic diastolic dysfunction displaces myosin heads from actin in the beating heart2012

    • Author(s)
      Pearson J, Jenkins M, Edgley AJ, Sonobe T, Schwenke DO, Fujii Y, Kelly D, Yagi N, Shirai M.
    • Organizer
      24^<th> Meeting of the International Society of Hypertension
    • Place of Presentation
      Sydney (Australia)
    • Year and Date
      2012-10-04
    • Related Report
      2012 Final Research Report
  • [Presentation] SPring-8放射光画像の心血管機能・再生研究への応用2012

    • Author(s)
      白井幹康
    • Organizer
      第11回日本再生医療学会
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-14
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 意識下ラットおよびマウスにおける運動時心筋血流の直接計測2012

    • Author(s)
      土持裕胤、曽野部崇、白井幹康
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-30
    • Related Report
      2012 Final Research Report
  • [Presentation] 麻酔下マウスにおける心臓迷走神経終末からのアセチルコリン分泌モニタリング-マイクロダイアリシス法を用いて-2012

    • Author(s)
      戦冬雲、杜成坤、秋山剛、曽野部崇、白井幹康
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-30
    • Related Report
      2012 Final Research Report
  • [Presentation] 心筋間質5-HTとモノアミンオキシダーゼによる5-HIAAの同時モニタリング2012

    • Author(s)
      杜成坤、戦冬雲、秋山剛、曽野部崇、白井幹康
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-30
    • Related Report
      2012 Final Research Report
  • [Presentation] 心虚血再灌流時の心筋間質中セロトニン動態-再取り込み・代謝の寄与-2012

    • Author(s)
      曽野部崇、秋山剛、杜成坤、戦冬雲、白井幹康
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-30
    • Related Report
      2012 Final Research Report
  • [Presentation] 放射光微小血管造影法によるラット糖尿病冠動脈内皮障害の初期病態の検出2012

    • Author(s)
      白井幹康、ジェンキンス・マシュー、ピアソン・ジェームズ、曽野部崇、藤井豊、土持裕胤、吉本光佐、梅谷啓二
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 2-kidney, 1-clip Goldblatt (2K1C)高血圧ラットモデルでの腎臓交感神経活動と動脈圧の変化2012

    • Author(s)
      吉本光佐、曽野部崇、藤井豊、三木健寿、白井幹康
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] ダール食塩感受性ラットの高血圧発症初期における交感神経活動の変化2012

    • Author(s)
      峯山直子、吉本光佐、大西由美子、白井幹康、三木健寿
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 人工灌流時の病態生理学研究のためのラット小型体外循環システムの構築2012

    • Author(s)
      藤井豊、白井幹康、稲盛修二、武輪能明、巽英介、妙中義之
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] アナフィラキシーショックによるラット門脈の血管収縮応答2012

    • Author(s)
      柳田洋、下内章人、曽野部崇、シュエンキ・ダリル、白井幹康
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] In vivo dynamic synchrotron imaging of coronary endothelial dysfunction in rats with early stage diabetes.2012

    • Author(s)
      Shirai M, Jenkins M, Pearson J, Sonobe T, Fujii Y, Tsuchimochi H, Yoshimoto M, Umetani K
    • Organizer
      89th Annual Meeting of the Physiological Society of Japa
    • Place of Presentation
      松本市総合体育館(長野)
    • Related Report
      2011 Research-status Report
  • [Presentation] Rho-kinase inhibition improves localised coronary dysfunction in vivo, in the diabetic microcirculation2011

    • Author(s)
      Jenkins M, Shirai M, Edgley AJ, Kelly DJ, Pearson J, Sonobe T, Umetani K, Brown R, Schwenke DO.
    • Organizer
      European Society of Cardiology Congress
    • Place of Presentation
      Paris (France)
    • Year and Date
      2011-08-27
    • Related Report
      2012 Final Research Report
  • [Presentation] 放射光X線機能画像の循環器研究への応用2011

    • Author(s)
      白井幹康
    • Organizer
      第23回北摂循環器研究会
    • Place of Presentation
      大阪
    • Year and Date
      2011-05-10
    • Related Report
      2012 Final Research Report
  • [Presentation] Rho-kinase inhibition improves localised coronary dysfunction in vivo, in the diabetic microcirculation.2011

    • Author(s)
      Jenkins M, Shirai M, Edgley AJ, Kelly DJ, Pearson J, Sonobe T, Umetani K, Brown R, Schwenke DO
    • Organizer
      European Society of Cardiology Congress
    • Place of Presentation
      パリ(フランス)
    • Related Report
      2011 Research-status Report
  • [Presentation] 放射光X線機能画像の循環器研究への応用2011

    • Author(s)
      白井幹康
    • Organizer
      第23回北摂循環器研究会(招待講演)
    • Place of Presentation
      大阪大学(大阪)
    • Related Report
      2011 Research-status Report
  • [Presentation] Abnormal cross-bridge dynamics in the in situ beating rat heart in early diabetes

    • Author(s)
      Shirai M, Jenkins M, Sonobe T, Fujii Y, Tsuchimochi H, Yoshimoto M, Inagaki T, Yagi N
    • Organizer
      90th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Early diabetic diastolic dysfunction displaces myosin heads from actin the beating heart

    • Author(s)
      Pearson J, Jenkins M, Edgley AJ, Sonobe T, Schwenke DO, Fujii Y, Kelly D, Yagi N, Shirai M.
    • Organizer
      24th Meeting of the International Society of Hypertension
    • Place of Presentation
      Sydney
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] SPring-8 Research Frontiers 2010. 財団法人高輝度光科学研究センター編集2011

    • Author(s)
      Schwenke DO, Umetani K, and Shirai M.
    • URL

      http://www.spring8.or.jp/pdf/en/res_fro/10/036-037.pdf

    • Related Report
      2012 Final Research Report
  • [Book] SPring-8 Research Frontiers 20102011

    • Author(s)
      Schwenke DO, Umetani K, and Shirai, M
    • Total Pages
      2
    • Publisher
      財団法人高輝度光科学研究センター
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.ncvc.go.jp/res/divisions/cardiac_physiology/index.html

    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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