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Integrated analysis of arrhythmogenic substrates in right ventricular outflow tract for the genesis of the lethal ventricular arrhythmia.

Research Project

Project/Area Number 16K08682
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionShowa University (2017-2019)
Kyoto Prefectural University of Medicine (2016)

Principal Investigator

Matsuyama Takaaki  昭和大学, 医学部, 教授 (40349113)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords刺激伝導系 / 不整脈原性器質 / プルキンエ線維 / 心室性不整脈 / カルシウム動態 / 虚血 / 病理形態 / 不整脈器質 / 病理組織学 / 異常伝導路 / 右室流出路 / 心筋配列 / 再分極異常 / 異常興奮 / 組織学 / 病理学 / 循環器 / 不整脈
Outline of Final Research Achievements

Recently, the region of right ventricular outflow tract (RVOT) has been highlighted as an arrhythmogenic substrate, however, its morphologic characteristics for arrhythmogenesis still remains unclear. In the present study, we assumed that the endocardial Purkinje fiber network is a crucial arrhythmogenic structure in the ventricle, and visualized electrical excitation patterns and intracellular calcium dynamics using fluorescent imaging in mouse heart myocardial infarct model. Irregular and slower impulse propagations were observed at the bordr of the infarction, and Purkinje fibers in the peri-infarct zone exhibited non-uniform intracellular calcium dynamics (beat-to-beat alternans of the calcium transient). This electrical vulnerability of the Purkinje fiber network under ischemic condition was observed as the unstable intracellular calcium dynamics at the border of the infarcted area. This phenomenon might be associated with the genesis of lethal ventricular arrhythmia.

Academic Significance and Societal Importance of the Research Achievements

致死性不整脈の発生源の一つとして心室内の特殊な構造で刺激伝導系の末梢にあるプルキンエ線維の存在が臨床的にも注目されているが、実際にどのように機能障害を生じて不整脈源性を発揮しているのは明らかではない。本研究では心室性不整脈の発生につながる可能性のある電気生理学的異常がどのような形態学的基盤を基にして生じているのかを肉眼的かつ組織学的にも視覚的に示すことができた。心室の致死性不整脈の発生機序を解明する上で、このような生きた心臓の電気生理学的現象の視覚的情報はその病態の理解を深め、さらにそれに対するより有効な治療方法の開発の一助となる可能性を秘めている。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (35 results)

All 2019 2018 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Int'l Joint Research: 4 results) Book (4 results)

  • [Journal Article] Occurrence of a primary liver cancer with an unusual histologic appearance as a late Fontan complication2019

    • Author(s)
      Matsuyama Taka-aki、Ohuchi Hideo、Saito Koji、Kondo Fukuo、Fukusato Toshio、Ishibashi-Ueda Hatsue
    • Journal Title

      Pathology - Research and Practice

      Volume: 215 Issue: 6 Pages: 152366-152366

    • DOI

      10.1016/j.prp.2019.02.016

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 不整脈の既往がある心臓を解剖するために知っておきたいこと2019

    • Author(s)
      松山高明
    • Journal Title

      診断病理

      Volume: 36 Pages: 7-14

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 正常心臓解剖の再考 心房・心室の解剖2019

    • Author(s)
      松山 高明, 曽根 浩元
    • Journal Title

      Heart View

      Volume: 23 Pages: 128-134

    • Related Report
      2018 Research-status Report
  • [Journal Article] Three-dimensional histologic reconstruction of remnant functional accessory atrioventricular myocardial connections in a case of Wolff-Parkinson-White syndrome2018

    • Author(s)
      Matsuyama Taka-aki、Haraguchi Ryo、Nakashima Junko、Kusano Kengo、Ishibashi-Ueda Hatsue
    • Journal Title

      Cardiovascular Pathology

      Volume: 37 Pages: 1-4

    • DOI

      10.1016/j.carpath.2018.07.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathology after a combination of sequential and simultaneous unipolar radiofrequency ablation of ventricular tachycardia in a postmortem heart with cardiac sarcoidosis2018

    • Author(s)
      Miyamoto Koji、Matsuyama Taka-aki、Noda Takashi、Ishibashi-Ueda Hatsue、Kusano Kengo
    • Journal Title

      Clinical Case Reports

      Volume: 6 Issue: 7 Pages: 1219-1224

    • DOI

      10.1002/ccr3.1577

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatiotemporally Non-Uniform Ca2+ Dynamics of Cardiac Purkinje Fibers in Mouse Myocardial Infarct2017

    • Author(s)
      Matsuyama Taka-aki、Tanaka Hideo、Ishibashi-Ueda Hatsue、Takamatsu Tetsuro
    • Journal Title

      Journal of Histochemistry & Cytochemistry

      Volume: 65 Issue: 11 Pages: 655-667

    • DOI

      10.1369/0022155417730280

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Towards an integrated understanding of cardiac arrhythmogenesis - Growing roles of expermental pathology.2017

    • Author(s)
      Tanaka H, Matsuyama T, Takamatsu T
    • Journal Title

      Pathology International

      Volume: 67 Issue: 1 Pages: 8-16

    • DOI

      10.1111/pin.12487

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 副伝導路を組織学的に示されたB 型WPW症候群の突然死の一例2019

    • Author(s)
      松山高明, 曽根浩元, 橋本茉莉, 簑原沙和, 藤城雅也, 李暁鵬, 瀧本雅文 ,畠山金太, 大林千穂, 羽竹勝彦
    • Organizer
      第108回 日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 三尖弁輪の副伝導路を組織学的に示し得た WPW 症候群の突然死の一例2019

    • Author(s)
      松山 高明, 橋本 茉莉, 簑原 沙和, 藤城 雅也, 李 暁鵬, 佐藤 啓造
    • Organizer
      第103次 日本法医学会学術全国集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Histologic features of the right and left side bundle of Kent; two autopsy cases of WPW syndrome.2019

    • Author(s)
      Taka-aki Matsuyama, Ryo Haraguchi, Kengo Kusano, Ishibashi-ueda Hatsue, Kinta Hatakeyama, Katsuhiko Hatake
    • Organizer
      第66回日本不整脈心電学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 連続切片標本を用いた肥大型心筋症の異常心筋配列の立体構造解析2019

    • Author(s)
      曽根 浩元, 松山 高明. 高木 孝士, 本田一穂, 鈴木洋
    • Organizer
      第60回日本組織細胞化学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 副伝導路症候群を有する急死事例の房室接合部異常心筋の解析2019

    • Author(s)
      松山 高明, 橋本 茉莉, 簑原 沙和, 曽根 浩元, 藤城 雅也, 李 暁鵬, 城 祐一郎, 佐藤 啓造, 羽竹 勝彦, 今井 美智子, 井出 宗則
    • Organizer
      第2回日本法医病理学会学術全国集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高血圧性心疾患および虚血性心疾患に起因した心室頻拍に対するカテーテルアブレーション治療に難渋した 1 剖検例2019

    • Author(s)
      松山高明, 植田初江, 中原志朗, 田口功
    • Organizer
      カテーテルアブレーション関連秋季大会2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 心房細動に対する肺静脈隔離術後 25 日目に脳梗塞で発症した左房食道瘻の 1 剖検例2019

    • Author(s)
      松山高明, 伊藤啓之, 河村光晴, 児玉雄介, 三浦咲子, 瀧本雅文, 小林洋一, 新家俊郎
    • Organizer
      カテーテルアブレーション関連秋季大会2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 三尖弁輪の副伝導路を組織学的に確認できたB型WPW症候群の突然死の2 例2019

    • Author(s)
      松山高明, 曽根浩元, 橋本茉莉, 簑原沙和, 加藤祐樹, 畠山金太, 大林千穂, 羽竹勝彦, 今井 美智子, 井出 宗則
    • Organizer
      第32回心臓性急死研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 心筋カルシウム動態の時空的均一性 横行小管の発現との関連2018

    • Author(s)
      田中秀央, 松山高明, 髙松哲郎
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒト心臓房室刺激伝導系組織の立体画像再構築2018

    • Author(s)
      松山 高明, 高木 孝士, 曽根 浩元, 本田 一穂, 原口 亮, 植田 初江, 田中 秀央
    • Organizer
      第59回日本組織細胞化学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Subtle lesions probably associated with lethal cardiac events in the heart; 3 cases of non-forensic autopsy2018

    • Author(s)
      Taka-aki Matsuyama, Mari Hashimoto, Masaya Fujishiro, Noriko Nemoto, Xiao-Pen Lee, Masafumi Takimoto, Keizo Sato
    • Organizer
      24th Congress of the International Academy of Legal Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Suspected of non-compaction cardiomyopathy in a heart failure case of double outlet of right ventricle in left isomerism2018

    • Author(s)
      Taka-aki Matsuyama, Hideo Tanaka, Mihoko Yamaguchi, Siew Yen Ho
    • Organizer
      The Weinstein Cardiovascular Development and Regeneration Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 心筋細胞の好塩基性変性の臨床的意義2018

    • Author(s)
      松山高明, 曽根浩元, 佐藤俊弥, 塚本茂人, 新家俊郎, 九島巳樹, 小形岳寛, 田中秀央, 池田善彦
    • Organizer
      第 40 回 心筋生検研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 三尖弁輪に二重房室結節様組織を認めたフォンタン術後の両大血管右室起始症の1剖検例2018

    • Author(s)
      松山高明
    • Organizer
      第20回成人先天性心疾患学会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Morphological exploration of arrhythmogenic substrates for refractory ventricular arrhythmia in the autopised humans hearts after catheter ablation therapy2017

    • Author(s)
      Taka-aki Matsuyama
    • Organizer
      Japanese Heart Rhythm Society
    • Related Report
      2017 Research-status Report
  • [Presentation] 心筋炎の病理診断2017

    • Author(s)
      松山高明
    • Organizer
      第 106回 日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 心筋生検における炎症細胞の評価 -心筋炎とその鑑別疾患-2017

    • Author(s)
      松山高明
    • Organizer
      第 106回 日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 恒久型心臓ペースメーカリードの心内癒着部位の検討2017

    • Author(s)
      松山高明
    • Organizer
      第 106回 日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 高速共焦点レーザー顕微鏡でみた心筋梗塞後に残存するプルキンエ細胞の機能的変化2016

    • Author(s)
      松山高明、田中秀央、植田初江
    • Organizer
      第38回心筋生検研究会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト心臓刺激伝導系組織の連続切片による立体画像再構築2016

    • Author(s)
      松山 高明, 原口 亮, 植田 初江, 田中秀央
    • Organizer
      第57回日本組織細胞化学会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Beat-to-beat variability of intracellular Ca2+ dynamics of Purkinje cells in the infarct border zone of the mouse heart revealed by rapid-scanning confocal microscopy2016

    • Author(s)
      Taka-aki Matsuyama, Hideo Tanaka, Hatsue Ishibashi-Ueda, Tetsuo Takamatsu
    • Organizer
      第63回日本不整脈心電学会学術大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Beat-to-beat variability of intracellular Ca2+ dynamics of Purkinje cells in the infarct border zone of the mouse heart revealed by rapid-scanning confocal microscopy2016

    • Author(s)
      Taka-aki Matsuyama, Hideo Tanaka, Tetsuro Takamatsu
    • Organizer
      Frontiers in Cardiovascular Biology 2016
    • Place of Presentation
      Florence, Italy
    • Year and Date
      2016-07-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Towards an integrated understanding of atrial arrhythmogenesis, combined fluorescence imaging of excitation and the relevant histological analysis in perfused rat heart2016

    • Author(s)
      Taka-aki Matsuyama, Hideo Tanaka
    • Organizer
      Gordon Research Conference Cardiac Regulatory Mechanisms
    • Place of Presentation
      New London, NH, USA
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 心筋梗塞後に心内膜面に残存するプルキンエ細胞の高速カルシウムイメージング法による機能解析2016

    • Author(s)
      松山高明、田中秀央、植田初江、高松哲郎
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
  • [Book] カテーテルアブレーションがうまくいくカラクリ2018

    • Author(s)
      松山高明
    • Total Pages
      340
    • Publisher
      メジカルビュー社
    • ISBN
      9784758314459
    • Related Report
      2017 Research-status Report
  • [Book] 診断モダリティとしての心筋病理2017

    • Author(s)
      松山高明
    • Total Pages
      214
    • Publisher
      南江堂
    • Related Report
      2016 Research-status Report
  • [Book] 循環器診療に活かす心臓血管解剖学2016

    • Author(s)
      松山高明
    • Total Pages
      213
    • Publisher
      メジカルビュー社
    • Related Report
      2016 Research-status Report
  • [Book] 心室頻拍のすべて2016

    • Author(s)
      松山高明
    • Total Pages
      343
    • Publisher
      南江堂
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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