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

• Kato Sara

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

• Honjo Haruo

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

• Takemoto Yoshio

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

• Takanari Hiroki

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Medical Physiology, University Medical Center Utrecht, The Netherlands Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Medical Physiology, University Medical Center Utrecht, The Netherlands

• Suzuki Tomoyuki

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

• Okuno Yusuke

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

• Opthof Tobias

  Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, The Netherlands Department of Medical Physiology, University Medical Center Utrecht, The Netherlands Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, The Netherlands Department of Medical Physiology, University Medical Center Utrecht, The Netherlands

• Sakuma Ichiro

  Graduate School of Engineering, The University of Tokyo, Japan Graduate School of Engineering, The University of Tokyo, Japan

• Inada Shin

  National Cardiovascular Center, Research Institute, Japan National Cardiovascular Center, Research Institute, Japan

• Nakazawa Kazuo

  National Cardiovascular Center, Research Institute, Japan National Cardiovascular Center, Research Institute, Japan

• Ashihara Takashi

  Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Japan Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Japan

• Kodama Itsuo

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

• Kamiya Kaichiro

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

Bibliographic Information

Other Title

• Pharmacological Blockade of IKs Destabilizes Spiral-Wave Reentry Under β-Adrenergic Stimulation in Favor of Its Early Termination
• Pharmacological Blockade of <I>I</I><SUB>Ks</SUB> Destabilizes Spiral-Wave Reentry Under <I>&beta;</I>-Adrenergic Stimulation in Favor of Its Early Termination

Abstract

We tested a hypothesis that an enhancement of I_Ks 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 μM) significantly shortened action potential duration (APD); chromanol 293B (30 μM), a selective I_Ks-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 μM), a selective I_Kr-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, β-adrenergic stimulation stabilizes SW reentry most likely though an enhancement of I_Ks. Blockade of I_Ks may be a promising therapeutic modality in prevention of ventricular tachyarrhythmias under high sympathetic activity.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 119 (1), 52-63, 2012

  The Japanese Pharmacological Society

Keywords

• <I>β</I>-adrenergic stimulation
• <I>I</I><SUB>Ks</SUB>
• spiral-wave reentry
• optical mapping
• ventricular tachycardia

Details

• CRID: 1390001205178308864
• NII Article ID: 10030760299
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.12008fp
• COI: 1:CAS:528:DC%2BC38XnvVKns70%3D
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 023634680
• PubMed: 22641132
• Web Site: http://repo.lib.tokushima-u.ac.jp/118223
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023634680
• Text Lang: en
• Data Source:
  • JaLC
  • IRDB
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed