氏名（所属）：
稲田慎（国立循環器病研究センター）,原口亮（国立循環器病研究センター）,芦原貴司（滋賀医科大学循環器内科・不整脈センター，国立循環器病研究センター）,中沢一雄（国立循環器病研究センター）

概要：
スーパーコンピュータ上に仮想心臓モデルを構築し，電気生理学的シミュレーションを行うことで致死性不整脈のメカニズム解明や，予防・診断に役立たせることを目的としている．内容：心筋細胞の電気的興奮に伴う電気現象（活動電位）を再現することが可能なユニットを約2000万個組み合わせて心室形状モデルを構築した．モデルには，心室壁内における電気生理学的性質の不均一性（心室較差）を組み込んだ．本研究では，遺伝性の心臓疾患の一つであるBrugada症候群を想定し，伝導障害と心室性不整脈の誘発性および持続性との関係について検討した．その結果，伝導障害領域の大きさ，障害の程度，期外収縮のタイミングが不整脈の誘発性や持続性に影響を与えることがわかった．また，右室流出路における伝導障害は，右室自由壁に伝導障害がある場合と比較して，伝導障害領域における興奮波の広がりが不均一になりやすく，その結果，不整脈の誘発性が高くなることが明らかとなった．

 

論文掲載,発表実績:
（学術雑誌掲載論文）

• Fernande Freyermuth, Frederique Rau, Yosuke Kokunai, Thomas Linke, Chantal Sellier, Masayuki Nakamori, Yoshihiro Kino, Ludovic Arandel, Arnaud Jollet, Christelle Thibault, Muriel Philipps, Serge Vicaire, Bernard Jost, Bjarne Udd, John W. Day, Denis Duboc, Karim Wahbi, Tsuyoshi Matsumura, Harutoshi Fujimura, Hideki Mochizuki, François Deryckere, Takashi Kimura, Nobuyuki Nukina, Shoichi Ishiura, Vincent Lacroix, Amandine Campan-Fournier, Vincent Navratil, Emilie Chautard, Didier Auboeuf, Minoru Horie, Keiji Imoto, Kuang-Yung Lee, Maurice S. Swanson, Adolfo Lopez de Munain, Shin Inada, Hideki Itoh, Kazuo Nakazawa, Takashi Ashihara, Eric Wang, Thomas Zimmer, Denis Furling, Masanori P. Takahashi, Nicolas Charlet-Berguerand. Splicing misregulation of SCN5A contributes to cardiac conduction delay and heart arrhythmia in myotonic dystrophy. Nature Communications. 2016 (accepted).

 

（国際会議会議録掲載論文）

• Kensuke Sakata, Takashi Ashihara, Tomoya Ozawa, Koichi Kato, Takeshi Tsuchiya, Ryo Haraguchi, Shin Inada, Kazoo Nakazawa, Minoru Horie. No stationary rotors are observed in patients with non-paroxysmal atrial fibrillation: A combined clinical and in silico study employing a novel real-time phase mapping system (ExTRa Mapping). The 8th Asia-Pacific Heart Rhythm Society Scientific Session (APHRS) (2015/11/19-22, Melbourne, poster presentation).

  Takashi Ashihara, Kensuke Sakata, Tomoya Ozawa, Koichi Kato, Takeshi Tsuchiya, Ryo Haraguchi, Shin Inada, Kazoo Nakazawa, Minoru Horie. Development of a novel real-time phase mapping system, called ExTRa Mapping, using in silico technique for identifying unstable rotors in patients with non-paroxysmal atrial fibrillation. The 8th Asia-Pacific Heart Rhythm Society Scientific Session (APHRS) (2015/11/19-22, Melbourne, poster presentation).

  Takashi Ashihara, Kensuke Sakata, Tomoya Ozawa, Koichi Kato, Takeshi Tsuchiya, Ryo Haraguchi, Shin Inada, Kazuo Nakazawa, Minoru Horie. Rotor distribution does not always match with the anatomic distribution of complex fractionated atrial electrogram sites in patients with non-paroxysmal atrial fibrillation: A clinical observational study employing a novel real-time phase mapping system (ExTRa Mapping). The 8th Asia-Pacific Heart Rhythm Society Scientific Session (APHRS) (2015/11/19-22, Melbourne, oral presentation).

  Shin Inada, Takeshi Aiba, Daniel T. Harrell, Ryo Haraguchi, Takashi Ashihara, Naomasa Makita, Wataru Shimizu, Takanori Ikeda, Kazuo Nakazawa: Conduction delay of right ventricular outflow tract and ventricular arrhythmia - A simulation study for Brugada syndrome -, International Congress on Electrocardiology 2015 (2015/6/24-27, Brazil, oral presentation).

  Takashi Ashihara, Tomoya Ozawa, Tetsuhisa Hattori, Koichi Kato, Takeshi Tsuchiya, T Yamaguchi, R Haraguchi, Shin Inada, Kazuo Nakazawa, Minoru Horie. Possible mechanisms of rotor ablation for chronic atrial fibrillation: A simulation study. Heart Rhythm 2015 Scientific Sessions (2015/5/13-16, Boston, poster presentation).

 

（国内研究会等発表論文）

• Shin Inada, Daniel T. Harrell, Ryo Haraguchi, Takashi Ashihara, Takeshi Aiba, Fumiyoshi Yamashita, Nitaro Shibata, Takanori Ikeda, Kazuyuki Mitsui, Naomasa Makita, Haruo Honjo, Mark R. Boyett, Kazuo Nakazawa. Multi-scale simulation studies of excitation conduction including cardiac conduction systems and whole ventricles. 第93会日本生理学会大会（2016/3/22-24，札幌，シンポジウム）．

  Shin Inada, Takeshi Aiba, Ryo Haraguchi, Takashi Ashihara, Kengo Kusano, Wataru Shimizu, Takanori Ikeda, Kazuo Nakazawa. Non-invasive risk stratification of ventricular arrhythmias intiated from right ventricular outflow tract: A simulation study for the Brugada syndrome. 第80回日本循環器学会学術集会（2016/3/18-20, 仙台，口頭発表）．

  Takashi Ashihara, Kensuke Sakata, Tomoya Ozawa, Takeshi Tsuchiya, Ryo Haraguchi, Shin Inada, Kazoo Nakazawa, Minoru Horie. The Current Status and the Future Direction: Significance of online real-time phase mapping during catheter ablation for non-paroxysmal atrial fibrillation: A clinical study using ExTRa Mapping system. 第80回日本循環器学会学術集会（2016/3/18-20, 仙台，プレナリーセッション）．

  芦原貴司，小澤友哉，坂田憲佑，土谷健，原口亮，稲田慎，中沢一雄，堀江稔．慢性心房細動のアブレーション治療におけるイノベーション創出に向けたin silicoの挑戦．第24回日本コンピュータ外科学会大会（2015/11/21-23，東京，シンポジウム，口頭発表）．

  稲田慎，吉田秀哉，相庭武司，山下富義，中沢一雄：Naチャネルの変異に伴う心室筋細胞活動電位の変化のシミュレーション．第35回医療情報学連合大会（2015/11/1-4，沖縄，ポスター発表）．

  稲田慎，竹村匡正，鈴木信宏，芦原貴司，三井和幸，柴田仁太郎，中沢一雄．心房での不整脈起源の同定を目指した12誘導心電図解析システムの開発．第35回医療情報学連合大会（2015/11/1-4，沖縄，口頭発表）．

  坂田憲祐，芦原貴司，小澤友哉，土谷健，原口亮，稲田慎，中沢一雄，堀江稔．慢性心房細動に治療標的となるような定在ローターは存在するか？: ExTRa Mappingによる臨床的観察研究．第31回心電情報処理ワークショップ（2015/10/24-25，名古屋，口頭発表）．

  芦原貴司，坂田憲祐，小澤友哉，土谷健，原口亮，稲田慎，中沢一雄，堀江稔．慢性心房細動アブレーションにおけるイノベーション実現に向けたin silicoの挑戦: ExTRa Mappingの開発．第31回心電情報処理ワークショップ（2015/10/24-25，名古屋，口頭発表）．

  稲田慎，柴田仁太郎，竹村匡正，鈴木信宏，芦原貴司，三井和幸，中沢一雄．心房の異常自動能発生部位の同定を目指した心電図心房波解析手法の検討．第31回心電情報処理ワークショップ（2015/10/24-25，名古屋，口頭発表）．

  重文将，稲田慎，伊井仁志，中沢一雄，和田成生．興奮伝播様式が左心室変形挙動の与える影響．日本機械学会第26回バイオフロンティア講演会（2015/10/2-3, 福岡, 口頭発表）．

  中沢一雄，小山裕己，中島一崇，井尻敬，稲田慎，黒嵜健一，白石公，五十嵐健夫．先天性心疾患の心臓レプリカの機能を補完しコンシューマレベルのコンピュータで実用可能なマルチタッチブラウザ．第６３回日本心臓病学会学術集会（2015/9/18-20, 横浜，ビジュアルワークショップ４：生きた心臓を心臓シミュレーションで再現, 招待講演）．

  Shin Inada, Daniel T. Harrell, Ryo Haraguchi, Takashi Ashihara, Takeshi Aiba, Takanori Ikeda, Kazuyuki Mitsui, Haruo Honjo, Nitaro Shibata, Naomasa Makita, Kaichiro Kamiya, Itsuo Kodama, Kazuo Nakazawa: Can computer simulation technique contribute regenerative medicine? The 30th Annual Meeting of the Japanese Heart Rhythm Society and The 32nd Annual Scientific Meeting of the Japanese Society of Electrocardiology (Kyoto, 2015/7/28-31, symposium), Program and Abstracts, p. 396, 2015.

  Shin Inada, Nitaro Shibata, Takashi Ashihara, Kazuyuki Mitsui, Kazuo Nakazawa: Analyzing 12 lead ECG to predict the origin of premature ventricular contraction, The 30th Annual Meeting of the Japanese Heart Rhythm Society and The 32nd Annual Scientific Meeting of the Japanese Society of Electrocardiology (Kyoto, 2015/7/28-31, oral presentation), Program and Abstracts, p. 518, 2015.

  Akira Fukui, Takeshi Tsuchiya, Takanori Yamaguchi, Yasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara: A case with a stable rotor observed during atrial fibrillation using a novel phase mapping system called “ExTRa Mapping”, The 30th Annual Meeting of the Japanese Heart Rhythm Society and The 32nd Annual Scientific Meeting of the Japanese Society of Electrocardiology (Kyoto, 2015/7/28-31, poster presentation), Program and Abstracts, p. 613, 2015.

  Akira Fukui, Takeshi Tsuchiya, Takanori Yamaguchi, Yasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara: Site with repetitively appearing rotors exhibits high dominant frequency (DF) in atrial fibrillation (AF): An analysis with a novel phase mapping system called “ExTRa Mapping”, The 30th Annual Meeting of the Japanese Heart Rhythm Society and The 32nd Annual Scientific Meeting of the Japanese Society of Electrocardiology (Kyoto, 2015/7/28-31, oral presentation), Program and Abstracts, p. 538, 2015.

  Akira Fukui, Takeshi Tsuchiya, Takanoro Yamaguchi, Tasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara: Low voltage zone (LVZ) is closely related to repetitively appearing rotors: An analysis with a novel phase mapping system called “ExTRa Mapping”, The 30th Annual Meeting of the Japanese Heart Rhythm Society and The 32nd Annual Scientific Meeting of the Japanese Society of Electrocardiology (Kyoto, 2015/7/28-31, oral presentation), Program and Abstracts, p. 407, 2015.

  Akira Fukui, Takeshi Tsuchiya, Takanori Yamaguchi, Tasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara: Newly development near-real-time phase mapping system called “ExTRa Mapping” nicely elucidates rotors and it was preferentially located at fibrotic tissue border, The 30th Annual Meeting of the Japanese Heart Rhythm Society and The 32nd Annual Scientific Meeting of the Japanese Society of Electrocardiology (Kyoto, 2015/7/28-31, oral presentation), Program and Abstracts, p. 514, 2015.

  Takashi Ashihara, Ryo Haraguchi, Shin Inada, Kazuo Nakazawa, Takeshi Tsuchiya, Takanori Yamaguchi, Akira Fukui, Tomoya Ozawa, Tetsuhisa Hattori, Koichi Kato, Minoru Horie: Possible mechanisms of effective rotor ablation for chronic atrial fibrillation: A simulation study, The 30th Annual Meeting of the Japanese Heart Rhythm Society and The 32nd Annual Scientific Meeting of the Japanese Society of Electrocardiology (Kyoto, 2015/7/28-31, oral presentation), Program and Abstracts, p. 514, 2015.

  Takashi Ashihara, Tomoya Ozawa, Takeshi Tsuchiya, Takanori Yamaguchi, Akira Fukui, Ryo Haraguchi, Shin Inada, Kazuo Nakazawa, Minoru Horie: Development of a novel real-time phase mapping system using in silico technique for identifying unstable rotors in human atrial fibrillation, The 30th Annual Meeting of the Japanese Heart Rhythm Society and The 32nd Annual Scientific Meeting of the Japanese Society of Electrocardiology (Kyoto, 2015/7/28-31, oral presentation), Program and Abstracts, p. 407, 2015.

  芦原貴司，黒川洵子，諫田泰成，関野祐子，原口亮，稲田慎，中沢一雄，堀江稔．In SilicoヒトiPS細胞由来心筋細胞の構築と不整脈研究への応用可能性．第51回日本小児循環器学会総会・学術集会（2015/7/16-18，口頭発表，東京）．

  中沢一雄，井尻敬，小山裕己，中島一崇，五十嵐健夫，稲田慎，原口亮，奈良崎大士，岩田倫明，芦原貴司，神崎歩，黒嵜健一，坂口平馬，市川肇，白石公．先天性心疾患心臓の形状抽出と心臓レプリカを想定したマルチタッチブラウザ開発．第51回日本小児循環器学会総会・学術集会（2015/7/16-18，口頭発表，東京）．

  稲田慎，朝井隆裕，竹村匡正，鈴木信宏，芦原貴司，三井和幸，柴田仁太郎，中沢一雄：不整脈起源の同定を目指した12誘導心電図解析システムの開発，第54回日本生体医工学会大会（2015/5/7-9，名古屋市，oral presentation）．

  芦原貴司，小澤友哉，土谷健，原口亮，稲田慎，中沢一雄，堀江稔：慢性心房細動の新たな治療戦略に向けて：in silicoによるリアルタイムPhase Mappingシステムの開発，第54回日本生体医工学会大会（2015/5/7-9，名古屋，オーガナイズドセッション「心房細動維持機構の可視化と計算科学に基づく新たなアブレーション治療戦略の構築」）．

  Akira Fukui, Takanori Yamaguchi, Tasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara, Takeshi Tsuchiya: Rotor is not associated with complex fractionated atrial electrograms: A study with (quasi-)real-time mapping system called ExTRa Mapping, 第78回日本循環器学会学術集会（2015/4/24-26, 大阪市, oral presentation）．

  Akira Fukui, Takanori Yamaguchi, Tasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara, Takeshi Tsuchiya: Detection of rotors during atrial fibrillation (AF) using a newly developed (quasi-)real-time phase mapping system called ExTRa Mapping, 第78回日本循環器学会学術集会（2015/4/24-26, 大阪市, oral presentation）．

  Akira Fukui, Takanori Yamaguchi, Tasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara, Takeshi Tsuchiya: A newly developed (quasi-)real-time phase mapping system called “ExTRa Mapping” is superior to NavX activation mapping to detect rotor, 第78回日本循環器学会学術集会（2015/4/24-26, 大阪市, oral presentation）．

  Takashi Ashihara, Tomoya Ozawa, Tetsuhisa Hattori, Koichi Kato, Takeshi Tsuchiya, Takanori Yamaguchi, Ryo Haraguchi, Shin Inada, Kazuo Nakazawa, Minoru Horie: Possible mechanisms of rotor ablation for chronic atrial fibrillation: A simulation study, 第78回日本循環器学会学術集会（2015/4/24-26, 大阪市, oral presentation）．

  Akira Fukui, Takanori Yamaguchi, Tasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara, Takeshi Tsuchiya: Rotor sites is related to high dominant frequency in human atrial fibrillation: A study with (quasi-)real-time phase mapping system, 第78回日本循環器学会学術集会（2015/4/24-26, 大阪市, oral presentation）．

  Akira Fukui, Takanori Yamaguchi, Tasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara, Takeshi Tsuchiya: Low voltage zone (LVZ) harbors roters: An analysis with a novel (quasi-)real-time phase mapping system called “ExTRa Mapping”, 第78回日本循環器学会学術集会（2015/4/24-26, 大阪市, oral presentation）．

  Akira Fukui, Takanori Yamaguchi, Yasutsugu Nagamoto, Shin Inada, Kazuo Nakazawa, Takashi Ashihara, Takashi Tsuchiya: Roter during atrial fibrillation frequently meanders along sites with fractionated electrogram, 第78回日本循環器学会学術集会（2015/4/24-26, 大阪市, oral presentation）．

 

（その他）

• 中沢一雄，稲田慎，原口亮，相庭武司，池田隆徳，芦原貴司：FSKイオンチャネルモデルを用いた心臓興奮伝播の機能的シミュレーション，生体医工学，Vol. 53, No. 3, pp. 151-159, 2015.

  稲田慎，Daniel T. Harrell, 原口亮，芦原貴司，蒔田直昌，中沢一雄：コンピュータシミュレーションによるプルキンエ線維起源の心室性不整脈発生機序の検討，生体医工学，Vol. 53, No. 3, pp. 106-114, 2015.

  芦原貴司，黒川洵子，諫田泰成，原口亮，稲田慎，中沢一雄，堀江稔：ヒトiPS細胞由来心筋細胞シートの不整脈研究への応用可能性：in silico不整脈学の観点から，生体医工学，Vol. 53, No. 3, pp. 100-105, 2015.