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Novel aspects for the role and therapy of autonomic nervous system in pulmonary hypertension toward right ventricular heart failure

Research Project

Project/Area Number 24659393
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Circulatory organs internal medicine
Research InstitutionKyushu University

Principal Investigator

HIROOKA Yoshitaka  九州大学, 医学(系)研究科(研究院), 教授 (90284497)

Co-Investigator(Kenkyū-buntansha) ABE Kohtaro  九州大学, 医学(系)研究科(研究院), 助教 (20588107)
KISHI Takuya  九州大学, 医学(系)研究科(研究院), 准教授 (70423514)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords循環器・高血圧 / 生理活性 / 生理学 / 薬剤反応性 / 神経科学
Outline of Final Research Achievements

Pulmonary arterial hypertension derives from pulmonary arterial hyper constriction, remodeling, and pathological changes. Pulmonary hypertension is difficult to treat and its prognosis is with right ventricular failure. In the present study, we investigated whether hemodynamic change and autonomic nervous system alteration would be responsible for the pathophysiology of pulmonary hypertension in contrast to the aspect of tumor-like changes.
We found that a novel endothelin receptor antagonist and a thrombin receptor blocker acted on pulmonary artery with relative selectivity thereby improved pathological changes with hemodynamic improvement in rats with pulmonary hypertension. Furthermore, we found that the mechanical reduction of pulmonary hypertension elicited similar beneficial effects.
We also found that sympathetic activation occurred in pulmonary hypertension and suggest the usefulness of cardiac sympathetic imaging in patients with pulmonary arterial hypertension.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 3 results) Presentation (20 results) (of which Invited: 2 results)

  • [Journal Article] Negative acute hemodynamic response to balloon pulmonary angioplasty does not predicate the long-term outcome in patients with chronic thromboembolic pulmonary hypertension.2015

    • Author(s)
      Hosokawa K, Abe K, Oi K, Mukai Y, Hirooka Y, Sunagawa K.
    • Journal Title

      International Journal of Cardiology

      Volume: 188 Pages: 81-83

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel dual endothelin receptor antagonist macitentan reverses severe pulmonary arterial hypertension in rats.2014

    • Author(s)
      Kunita-Takanezawa M, Abe K, Hirooka Y, Kuwabara Y, Hirano K, Oka M, Sunagawa K.
    • Journal Title

      J Cardiovasc Pharmacol.

      Volume: 64 Issue: 5 Pages: 473-80

    • DOI

      10.1097/fjc.0000000000000141

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 今後期待される肺高血圧症治療薬の展望.2014

    • Author(s)
      阿部 弘太郎、廣岡 良隆、砂川 賢二
    • Journal Title

      呼吸器内科

      Volume: 26 Pages: 300-304

    • NAID

      40020251438

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 特発性肺動脈性肺高血圧症はどんな病気2013

    • Author(s)
      阿部弘太郎、廣岡良隆、砂川賢二
    • Journal Title

      Heart View

      Volume: 17 Pages: 24-29

    • Related Report
      2013 Research-status Report
  • [Journal Article] 肺高血圧症の成因2013

    • Author(s)
      阿部弘太郎、廣岡良隆、砂川賢二
    • Journal Title

      呼吸と循環

      Volume: 61 Pages: 1097-1103

    • Related Report
      2013 Research-status Report
  • [Journal Article] チロシンキナーゼ阻害薬の肺高血圧症治療薬としての展望2013

    • Author(s)
      阿部弘太郎、廣岡良隆、砂川賢二
    • Journal Title

      循環器内科

      Volume: 74 Pages: 615-619

    • NAID

      40019933697

    • Related Report
      2013 Research-status Report
  • [Journal Article] 特発性間質性肺炎にともなう肺高血圧症に対してボセンタンが奏効した1例2012

    • Author(s)
      阿部 弘太郎 他
    • Journal Title

      Modern Physician

      Volume: 32 Pages: 44-46

    • Related Report
      2012 Research-status Report
  • [Journal Article] 新しい肺高血圧症動物モデル2012

    • Author(s)
      阿部 弘太郎 他
    • Journal Title

      医学のあゆみ

      Volume: 240 Pages: 24-30

    • Related Report
      2012 Research-status Report
  • [Journal Article] Small-vessel diseaseと肺高血圧症2012

    • Author(s)
      阿部 弘太郎 他
    • Journal Title

      循環器内科2月号

      Volume: 71 Pages: 119-124

    • Related Report
      2012 Research-status Report
  • [Journal Article] 新しい肺高血圧症実験モデルからの知見2012

    • Author(s)
      阿部 弘太郎 他
    • Journal Title

      Cardiac Practice

      Volume: 24 Pages: 26-30

    • Related Report
      2012 Research-status Report
  • [Journal Article] Do Electrocardiography Scores Predict the Presence of Right Ventricular Dysfunction in Patients with Pulmonary Hypertension?2012

    • Author(s)
      Kohtaro Abe
    • Journal Title

      Internal Medicine

      Volume: 51 Issue: 17 Pages: 2261-2262

    • DOI

      10.2169/internalmedicine.51.8297

    • NAID

      130002062372

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Inhibition of Increased Thrombin Receptor Activity Attenuated Monocrotaline-induced Pulmonary Hypertension in Rats.2014

    • Author(s)
      Kuwabara Y, Abe K, Hirano M, Hirooka Y, Hirano K, Sunagawa K.
    • Organizer
      American Heart Association Scientific Sessions 2014
    • Place of Presentation
      Chicago
    • Year and Date
      2014-11-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肺高血圧症におけるトロンビン受容体PAR1の肺動脈収縮作用の亢進.2014

    • Author(s)
      桑原 志実、阿部 弘太郎、平野 真弓、廣岡 良隆、平野 勝也、砂川 賢二
    • Organizer
      第2回日本肺高血圧学会・第3回日本肺循環学会合同学術集会
    • Place of Presentation
      大手町サンケイプラザ
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 心臓交感神経シンチグラフィーを用いた肺高血圧症の非侵襲的な重症度評価法の確立.2014

    • Author(s)
      阿部 弘太郎、長尾 充展、廣岡 良隆、砂川 賢二
    • Organizer
      第62回日本心臓病学会学術集会
    • Place of Presentation
      仙台市民会館
    • Year and Date
      2014-09-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] トロンビン受容体拮抗薬はモノクロタリンによる肺高血圧の誘発を抑制する.2014

    • Author(s)
      桑原 志実、阿部 弘太郎、平野 真弓、廣岡 良隆、平野 勝也、砂川 賢二
    • Organizer
      第35回日本循環制御医学会総会
    • Place of Presentation
      九州大学医学部百年講堂
    • Year and Date
      2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Occlusive Vascular Remodeling Is A Consequence Of Hemodynamic Stress In Rats With Severe Pulmonary Arterial Hypertension.2014

    • Author(s)
      Abe K, Shinoda M, Kuwabara Y, McMurtry IF, Hirooka Y, Sunagawa K, Oka M.
    • Organizer
      American Thoracic Society International Conference 2014
    • Place of Presentation
      San Diego
    • Year and Date
      2014-05-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肺高血圧症における右室交感神経活動障害は、右心機能障害に比例する.2014

    • Author(s)
      阿部 弘太郎、廣岡 良隆、砂川 賢二
    • Organizer
      第54回日本呼吸器学会学術講演会
    • Place of Presentation
      リーガロイヤルホテル大阪
    • Year and Date
      2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Preventive effects of thrombin receptor antagonist on hemodynamic parameters and histological findings in monocrotaline-induced pulmonary hypertension rats.2014

    • Author(s)
      Kuwabara Y, Abe K, Hirano M, Hirooka Y, Hirano K, Sunagawa K.
    • Organizer
      第78回日本循環器学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] RV sympathetic dysfunction parallels RV performance in patients with pulmonary arterial hypertension.2014

    • Author(s)
      Abe K, Nagao M, Hirooka Y, Sunagawa K.
    • Organizer
      第78回日本循環器学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Left unilateral pulmonary artery banding prevents the development of plexogenic arteriopathy in rats with severe pulmonary arterial hypertension.2014

    • Author(s)
      Abe K, Oka M, Shinoda M, Kuwabara Y, McMurtry IF, Hirooka Y, Sunagawa K.
    • Organizer
      第78回日本循環器学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Long-term treatment with novel endothelin receptor antagonist macitentan markedly attenuated severe pulmonary hypertension with angioproliferative occlusive lesions in rats.2013

    • Author(s)
      Abe K, Kunita M, Hirooka Y, Kuwabara Y, Hirano K, Sunagawa K.
    • Organizer
      2013 American Thoracic Society International Conference
    • Place of Presentation
      フィラデルフィア(米国)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 新しいエンドセリン受容体拮抗薬、マシテンタンの慢性投与は肺高血圧モデルラットの病態進行を抑制する.2013

    • Author(s)
      國田 睦,阿部 弘太郎,廣岡 良隆,砂川 賢二.
    • Organizer
      第61回日本心臓病学会学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] A Novel endothelin receptor antagonist, macitentan markedly improved severe pulmonary arterial hypertension in rats by a near complete blockade of endothelin receptors.2013

    • Author(s)
      Kunita M, Abe K, Hirooka Y, Kuwabara Y, Hirano K, Sunagawa K.
    • Organizer
      Scientific Meeting of the American Heart Association 2013
    • Place of Presentation
      ダラス(米国)
    • Related Report
      2013 Research-status Report
  • [Presentation] Vasoconstriction is an important therapeutic target in severe pulmonaryarterial hypertension.2013

    • Author(s)
      阿部 弘太郎、廣岡 良隆、他
    • Organizer
      第77回日本循環器学会学術集会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] A new endothelin receptor antagonist macitentan is a potent vasodilatorin intrapulmonary arteries in rats with severe pulmonary hypertension.2013

    • Author(s)
      國田 睦、阿部 弘太郎、廣岡 良隆、他
    • Organizer
      第77回日本循環器学会学術集会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Interventricular dyssynchrony using Cine-tagging MRI predicts right ventricular dysfunction in patients with adult congenitla heart disease.2013

    • Author(s)
      長尾 充展、米澤 正人、阿部 弘太郎、他
    • Organizer
      第77回日本循環器学会学術集会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Chronic administration of proteinase-activated receptor 1 (PAR-1) antagonist attenuated monocrotaline-induced pulmonary hypertension in rats.2013

    • Author(s)
      桑原 志実、阿部 弘太郎、平野 勝也、廣岡 良隆、他
    • Organizer
      第77回日本循環器学会学術集会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 希少疾患である肺高血圧症の教育活動により心エコー技師への肺高血圧症に対する評価意識が高まる2013

    • Author(s)
      河原 吾朗、阿部 弘太郎、廣岡 良隆、他
    • Organizer
      第77回日本循環器学会学術集会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Cardiac Sympathetic Activity evaluated by 123I-MIBG Myocardial Scintigraphy in Patients with Right Ventricular Dysfunction Associated with Pulmonary Arterial Hypertension.2012

    • Author(s)
      阿部 弘太郎、廣岡 良隆、他
    • Organizer
      2013年米国胸部疾患学会総会
    • Place of Presentation
      サンフランシスコ(アメリカ)
    • Related Report
      2012 Research-status Report
  • [Presentation] Iodine-123-Metaiodobenzylguanidine (MIBG)心筋シンチグラフィを用いた肺動脈性肺高血圧症患者の右室の交感神経活動の評価2012

    • Author(s)
      阿部 弘太郎、廣岡 良隆、他
    • Organizer
      第33回日本循環制御医学会総会
    • Place of Presentation
      栃木
    • Related Report
      2012 Research-status Report
  • [Presentation] 心臓MRIによる三尖弁輪収縮期移動距離(TAPSE)は肺高血圧症患者の右心機能評価に有用である2012

    • Author(s)
      阿部 弘太郎、廣岡 良隆、他
    • Organizer
      第60回日本心臓病学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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