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

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概要

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• 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.

著者

• Ashihara Takashi

  Department Of Cardiovascular And Respiratory Medicine Heart Rhythm Center Shiga University Of Medica

• Nakazawa Kazuo

  National Cardiovascular Cenfer Research Institute

• Sakuma Ichiro

  Graduate School Of Engineering The Univ. Of Tokyo

• Takemoto Yoshio

  Department of Cardiovascular Research, Research Institute of Environmental Medichine, Nagoya Univers

• Honjo Haruo

  Department Of Applied Physics Faculty Of Engineering

• Okuno Yusuke

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Takanari Hiroki

  Department Of Cardiology Komaki City Hospital

• Opthof Tobias

  Experimental And Molecular Cardiology Groups Academic Medical Center

• Kamiya Kaichiro

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Kodama Itsuo

  Department Of Cardiovascular Research R.i.e.m. Nagoya University

• 本荘 晴朗

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Takagishi Y

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Suzuki Tomoyuki

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Kato Sara

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Inada Shin

  National Cardiovascular Center Research Institute

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