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PHARMACOTHERAPEUTIC STRATEGY FOR PREVENTION OF CARDIAC SUDDEN DEATH CAUSED BY VENTRICULAR REPOLARIZATION ABNORMALITY

Research Project

Project/Area Number 19590532
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionToho University

Principal Investigator

TAKAHARA Akira  Toho University, 薬学部, 准教授 (80377481)

Co-Investigator(Kenkyū-buntansha) 杉山 篤  山梨大学, 医学工学総合研究部, 准教授 (60242632)
Co-Investigator(Renkei-kenkyūsha) SUGIYAMA Atsushi  山梨大学, 医学工学総合研究部, 准教授 (60242632)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsQT延長症候群 / 心臓突然死 / 薬物治療 / N型Ca^<2+>チャネル / 心筋再分極異常 / 薬物治療戦略 / アップストリーム治療
Research Abstract

心筋再分極異常は致死的な不整脈を誘発する可能性が高いにも関わらず、このような危険を回避するアップストリーム治療法はこれまで十分に検討されていなかった。このような病態を反映するモデル動物を用いた本研究を遂行させた結果、抗高血圧薬シルニジピンはN型Ca2+チャネル抑制作用により心筋再分極異常を改善することが示された。N型Ca2+チャネルを選択的に抑制する新規薬物の創出は、心筋再分極異常を有する患者に対して血圧低下などの副作用がない薬物治療法として期待できる。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (41 results)

All 2009 2008 2007 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (23 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Long-term blockade of L/N-type Ca^<2+> channels by cilnidipine ameliorates repolarization abnormality of the canine hypertrophied heart.2009

    • Author(s)
      Takahara A, Nakamura Y, Wagatsuma H, Aritomi S, Nakayama A, Satoh Y, Akie Y, Sugiyama A
    • Journal Title

      Br. J. Pharmacol (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Utilities of a halothane-anesthetized, closed-chest, guinea pig as a model to assess the drug-induced QT-interval prolongation2009

    • Author(s)
      Sakaguchi Y, Takahara A, Nakamura Y, Akie Y, Sugiyama A
    • Journal Title

      Basic Clin. Pharmacol. Toxicol 104(1)

      Pages: 43-48

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic left atrial volume overload abbreviates the action potential duration of the canine pulmonary vein myocardium via activation of IK channel2008

    • Author(s)
      Nouchi H, Takahara A, Nakamura H, Namekata I, Sugimoto T, Tsuneoka Y, Takeda K, Tanaka T, Shigenobu K, Sugiyama A, Tanaka H
    • Journal Title

      Eur. J. Pharmacol 597(1-3)

      Pages: 80-84

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Beat-to-beat variability of repolarization differentiates the extent of torsadogenic potential of multi ion-channel blockers bepridil and amiodarone2008

    • Author(s)
      Takahara A, Nakamura Y, Sugiyama A
    • Journal Title

      Eur. J. Pharmacol 596(1-3)

      Pages: 127-131

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of electropharmacological effects of bepridil and sotalol in the halothane-anesthetized dogs2008

    • Author(s)
      Ishizaka T, Takahara A, Iwasaki H, Mitsumori Y, Kise H, Nakamura Y, Sugiyama A.
    • Journal Title

      Circ. J. 72(6)

      Pages: 1003-1011

    • NAID

      110006783841

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular mechanisms and receptor types for endothelin-1-induced positive and negative inotropy in mouse ventricular myocardium2008

    • Author(s)
      Namekata I, Fujiki S, Kawakami Y, Moriwaki R, Takeda K, Kawanishi T, Takahara A, Shigenobu K, Tanaka H.
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol 376(6)

      Pages: 385-395

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Beat-to-beat variability of repolarization differentiates the extent of torsadogenic potential of multi ion-channel blockers bepridil and amiodarone.2008

    • Author(s)
      高原 章
    • Journal Title

      European Journal of Pharmacology 596

      Pages: 127-131

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic left atrial volume overload abbreviates the action potential duration of the canine pulmonary vein myocardium via activation of IK channel.2008

    • Author(s)
      野内 秀明
    • Journal Title

      European Journal of Pharmacology 597

      Pages: 80-84

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of electropharmacological effects of bepridil and sotalol in the halothane-anesthetized dogs.2008

    • Author(s)
      石坂 智路
    • Journal Title

      Circulation Journal 72

      Pages: 1003-1011

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac effects of L/N-type Ca^<2+> channel blocker cilnidipine in anesthetized dogs.2007

    • Author(s)
      Takahara A, Iwasaki H, Nakamura Y, Sugiyama A.
    • Journal Title

      Eur. J. Pharmacol 565(1-3)

      Pages: 166-170

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cardiovascular profile of the canine torsades de pointes arrhythmia model assessed by echocardiographic and haemodynamic methods2007

    • Author(s)
      Takahara A, Sugiyama A, Satoh Y, Iwasaki H, Nakamura Y, Hashimoto K.
    • Journal Title

      Basic Clin. Pharmacol. Toxicol 101(1)

      Pages: 35-40

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cardiovascular profile of the canine torsades de pointes arrhythmia model assessed by echocardiographic and haemodynamic methods.2007

    • Author(s)
      高原 章
    • Journal Title

      Basic and Clinical Pharmacology and Toxicology 101

      Pages: 35-40

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac effects of L/N-type Ca^<2+> channel blocker cilnidipine in anesthetized dogs.2007

    • Author(s)
      高原 章
    • Journal Title

      European Journal of Pharmacology. 565

      Pages: 166-170

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular mechanisms and receptor types for endothelin-1-induced positive and negative inotropy in mouse ventricular myocardium.2007

    • Author(s)
      行方 衣由紀
    • Journal Title

      Naunyn-Schmiedeberg's Archives of Pharmacology 376

      Pages: 385-395

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chronic atrioventricular(AV)block sensitizes monkey heart for drug-induced Torsades de Pointes(TdP)via biochemicalbiochemical, anatomical and electrophysiological remodelings2009

    • Author(s)
      Sugiyama A, Nakamura Y, Saitoh M, Takahara A, Sakamoto K, Sasaki H, Hombo T, Wakasa Y, Nomura M
    • Organizer
      The 2007 Autumn Meeting of The British Society for Cardiovascular Research
    • Place of Presentation
      London
    • Year and Date
      2009-09-24
    • Related Report
      2008 Final Research Report
  • [Presentation] ハロセン麻酔モルモットモデルにおける鎮咳薬クロブチノールの心筋再分極相に与える作用 : 小動物用MAP記録カテーテルによる評価2009

    • Author(s)
      高原章、中村真理子、仙道晶子、行方衣由紀、田中光
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-18
    • Related Report
      2008 Final Research Report
  • [Presentation] モルモット肺静脈の心筋活動電位に対するベプリジルの影響 : 左心房に対する作用との比較2009

    • Author(s)
      竹田潔、杉本貴彦、行方衣由紀、高原章、田中光
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-18
    • Related Report
      2008 Final Research Report
  • [Presentation] ハロセン麻酔モルモットモデルにおける鎮咳薬クロブチノールの心筋再分極相に与える作用 : 小動物用MAP記録カテーテルによる評価.2009

    • Author(s)
      高原 章
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-03-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] ventricular myocardia2008

    • Author(s)
      Namekata I, Ohhara M, Hirota Y, Fukumoto M, Kawanishi T, Takahara A, Tanaka H.
    • Organizer
      The 25th Annual Meeting of ISHR Japanese Section
    • Place of Presentation
      Yokohama
    • Year and Date
      2008-12-05
    • Related Report
      2008 Final Research Report
  • [Presentation] モルモット肺静脈心筋における自発的電気活動の発生機序 : 選択的Na+^/Ca^<2+>交換機構阻害薬SEA0400を用いた検討2008

    • Author(s)
      行方衣由紀、恒岡弥生、杉本貴彦、竹田潔、島田英朗、高原章、田中光
    • Organizer
      第18回日本循環薬理学会
    • Place of Presentation
      千葉
    • Year and Date
      2008-11-21
    • Related Report
      2008 Final Research Report
  • [Presentation] 肺静脈自動能の発生機序の検討2008

    • Author(s)
      行方衣由紀、恒岡弥生、杉本貴彦、竹田潔、長治緑、川西徹、中村竜、高原章、田中光
    • Organizer
      第17回日本バイオイメージング学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2008-11-01
    • Related Report
      2008 Final Research Report
  • [Presentation] Arrhythmogenic property of the pulmonary vein myocardium in guinea pigs as a source of atrial fibrillation. The 9th World Conference on Clinical2008

    • Author(s)
      Takahara A, Sugimoto T, Takeda K, Tsuneoka Y, Kudo N, Namekata I, Tanaka H.
    • Organizer
      Pharmacology and Therapeutics
    • Place of Presentation
      Quebec
    • Year and Date
      2008-08-01
    • Related Report
      2008 Final Research Report
  • [Presentation] Arrhythmogenic Property of the Pulmonary Vein Myocardium in Guinea Pigs as a Source of Atrial Fibrillation.2008

    • Author(s)
      高原 章
    • Organizer
      The 9th World Conference on Clinical Pharmacology and Therapeutics
    • Place of Presentation
      Quebec City Convention Centre
    • Year and Date
      2008-08-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Chronic atrioventricular block abbreviated the action potential duration of canine pulmonary vein myocardium2008

    • Author(s)
      高原章、野内秀明、田中光、杉山篤
    • Organizer
      第72回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2008-03-29
    • Related Report
      2008 Final Research Report
  • [Presentation] Chronic atrioventricular block abbreviated the action potential duration of canine pulmonary vein myocardium.2008

    • Author(s)
      高原 章
    • Organizer
      第72回日本循環器学会学術集会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2008-03-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] L/T型カルシウム拮抗薬エホニジピンの反射性頻脈に対する抑制効果2008

    • Author(s)
      宇野洋司、高原章、田中光
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-18
    • Related Report
      2008 Final Research Report
  • [Presentation] 慢性房室ブロック犬心筋におけるK^+チャネルmRNAの発現抑制2008

    • Author(s)
      高原章、我妻広貴、有冨静、今田智之、秋江靖樹、杉山篤
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-18
    • Related Report
      2008 Final Research Report
  • [Presentation] モルモット摘出肺静脈の活動電位に対するカリウムチャネル抑制薬の影響2008

    • Author(s)
      杉本貴彦、野内秀明、高原章、田中光
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-18
    • Related Report
      2008 Final Research Report
  • [Presentation] 心筋の興奮・収縮機構の多様性2008

    • Author(s)
      田中光、行方衣由紀、野内秀明、高原章
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-18
    • Related Report
      2008 Final Research Report
  • [Presentation] 慢性房室ブロック犬心筋におけるK^+チャネルmRNA発現抑制2008

    • Author(s)
      高原 章
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2008-03-18
    • Related Report
      2007 Annual Research Report
  • [Presentation] 慢性完全房室ブロックモデル動物を用いた薬物性QT延長症候群のリスク評価2007

    • Author(s)
      杉山篤、佐藤吉沖、高原章
    • Organizer
      第24回日本心電学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-10-06
    • Related Report
      2008 Final Research Report
  • [Presentation] モルモット肺静脈の電気生理学的特性2007

    • Author(s)
      島田英朗、杉本貴彦、高原章、竹田潔、恒岡弥生、行方衣由紀、重信弘毅、田中 光
    • Organizer
      第24回日本心電学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-10-06
    • Related Report
      2008 Final Research Report
  • [Presentation] 鶏胚心筋を用いた薬物の催不整脈性評価法2007

    • Author(s)
      野内秀明、木股幹雄、桐生直明、高原章、田中光
    • Organizer
      第117回日本薬理学会関東部会
    • Place of Presentation
      東京
    • Year and Date
      2007-10-06
    • Related Report
      2008 Final Research Report
  • [Presentation] Utility of the embryonic chick ventricle as a new model to detect QT-interval prolonging drugs2007

    • Author(s)
      Namekata I, Takahara A, Nouchi H, Kimata M, Tsuruoka N, Shigenobu K, Tanaka H
    • Organizer
      The 2007 Autumn Meeting of The British Society for Cardiovascular Research
    • Place of Presentation
      London
    • Year and Date
      2007-09-24
    • Related Report
      2008 Final Research Report
  • [Presentation] Chronic Atrioventricular(AV)Block Sensitizes Monkey Heart for Drug-Induced Torsades de Pointes(TdP)via Biochemical, Anatomical and Electrophysiological Remodelings.2007

    • Author(s)
      杉山 篤
    • Organizer
      The 2007 Autumn Meeting of The British Society for Cardiovascular Research
    • Place of Presentation
      St. Thomas' Hospital
    • Year and Date
      2007-09-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] Embryonic chick myocardium as a sensitive model for prediction of drug-induced QT-interval prolongation2007

    • Author(s)
      Namekata I, Takahara A, Nouchi H, Kimata M, Shigenobu K, Tanaka H.
    • Organizer
      The 7th Annual Meeting of the Safety Pharmacology Society
    • Place of Presentation
      Edinburgh
    • Year and Date
      2007-09-20
    • Related Report
      2008 Final Research Report
  • [Presentation] 新規サル催不整脈モデルを用いたtorsades de pointes(TdP)リスク評価系の確立2007

    • Author(s)
      坂本憲吾、大谷光嗣、若狭芳男、高原章、杉山篤
    • Organizer
      第34回日本トキシコロジー学会学術年会
    • Place of Presentation
      東京
    • Year and Date
      2007-06-28
    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.mnc.toho-u.ac.jp/v-lab/shinkin/index.html

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.mnc.toho-u.ac.jp/v-lab/shinkin/index.html

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.mnc.toho-u.ac.jp/v-lab/shinkin/index.html

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 催不整脈モデル動物2008

    • Inventor(s)
      杉山篤、高原章、佐藤吉沖
    • Industrial Property Rights Holder
      株式会社イナリサーチ
    • Filing Date
      2008-02-29
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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