Pharmacological Blockade of I_<Ks> Destabilizes Spiral-Wave Reentry Under β-Adrenergic Stimulation in Favor of Its Early Termination

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著者

    • Kato Sara KATO Sara
    • Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
    • Honjo Haruo HONJO Haruo
    • Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
    • TAKANARI Hiroki
    • Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
    • SUZUKI Tomoyuki
    • Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
    • OKUNO Yusuke
    • Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
    • OPTHOF Tobias
    • Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center
    • INADA Shin
    • National Cardiovascular Center, Research Institute
    • ASHIHARA Takashi
    • Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
    • KODAMA Itsuo
    • Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
    • KAMIYA Kaichiro
    • Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University

抄録

We tested a hypothesis that an enhancement of <I>I</I><SUB>Ks</SUB> may play a pivotal role in ventricular proarrhythmia under high sympathetic activity. A 2-dimensional ventricular muscle layer was prepared in rabbit hearts, and action potential signals were analyzed by optical mapping. During constant stimulation, isoproterenol (ISP, 0.1 <I>μ</I>M) significantly shortened action potential duration (APD); chromanol 293B (30 <I>μ</I>M), a selective <I>I</I><SUB>Ks</SUB>-blocker, reversed the APD shortening. VTs induced in the presence of ISP lasted longer than in the control, and this was reversed by 293B. E-4031 (0.1 <I>μ</I>M), a selective <I>I</I><SUB>Kr</SUB>-blocker, did not cause such reversal. Spiral-wave (SW) reentry with ISP was characterized by more stable rotation around a shorter functional block line (FBL) than in the control. After application of 293B, SW reentry was destabilized, and rotation around a longer FBL with prominent drift reappeared. The APD abbreviation by ISP close to the rotation center was more pronounced than in the periphery, leading to an opposite APD gradient (center < periphery) compared with controls. This effect was also reversed by 293B. In conclusion, <I>β</I>-adrenergic stimulation stabilizes SW reentry most likely though an enhancement of <I>I</I><SUB>Ks</SUB>. Blockade of <I>I</I><SUB>Ks</SUB> may be a promising therapeutic modality in prevention of ventricular tachyarrhythmias under high sympathetic activity.

収録刊行物

  • Journal of pharmacological sciences

    Journal of pharmacological sciences 119(1), 52-63, 2012-05-20

    公益社団法人 日本薬理学会

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各種コード

  • NII論文ID(NAID)
    10030760299
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13478613
  • NDL 記事登録ID
    023634680
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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