Bepridil Facilitates Early Termination of Spiral-Wave Reentry in Two-Dimensional Cardiac Muscle Through an Increase of Intercellular Electrical Coupling

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• Bepridil is effective for conversion of atrial fibrillation to sinus rhythm and in the treatment of drug-refractory ventricular tachyarrhythmias. We investigated the effects of bepridil on electrophysiological properties and spiral-wave (SW) reentry in a 2-dimensional ventricular muscle layer of isolated rabbit hearts by optical mapping. Ventricular tachycardia (VT) induced in the presence of bepridil (1 μM) terminated earlier than in the control. Bepridil increased action potential duration (APD) by 5% – 8% under constant pacing and significantly increased the space constant. There was a linear relationship between the wavefront curvature (κ) and local conduction velocity: LCV = LCV0 − D·κ (D, diffusion coefficient; LCV0, LCV at κ = 0). Bepridil significantly increased D and LCV0. The regression lines with and without bepridil crossed at κ = 20 – 40 cm−1, resulting in a paradoxical decrease of LCV at κ > 40 cm−1. Dye transfer assay in cultured rat cardiomyocytes confirmed that bepridil increased intercellular coupling. SW reentry in the presence of bepridil was characterized by decremental conduction near the rotation center, prominent drift, and self-termination by collision with boundaries. These results indicate that bepridil causes an increase of intercellular coupling and a moderate APD prolongation, and this combination compromises wavefront propagation near the rotation center of SW reentry, leading to its drift and early termination.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.10233FP]

著者

• Ashihara Takashi

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

• Kodama Itsuo

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya Universi

• HARADA Masahide

  Department of Energy Conversion Engineering, Kyushu University

• Sakuma Ichiro

  Graduate School Of Engineering The Univ. Of Tokyo

• Honjou Haruo

  名古屋大学 循環器内科学

• Honjou Haruo

  Department Of Humoral Regulation Research Institute Of Environmental Medicine Nagoya University

• Honjo Haruo

  名古屋大学環境医学研究所

• Honjo Haruo

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Kamiya Kaichiro

  Department Of Humoral Regulation The Research Institute Of Environmental Medicine Nagoya University

• Takemura Haruki

  Division Of Cardiovascular Research Reseearch Institute Of Environmental Medicine Nagoya University

• Okuno Yusuke

  Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya Universi

• 高岸 芳子

  名古屋大学環境医学研究所

• Takagishi Yoshiko

  Department Of Teratology And Genetics Research Institute Of Environmental Medicine Nagoya University

• Takeuchi Yoko

  Department Of Genetics Research Institute Of Environmental Medicine

• Takagishi Yoshiko

  Research Institute Of Environmental Medicine Nagoya University

• Takemoto Yoshio

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

• Takanari Hiroki

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

• Kato Sara

  Department of Cardiovascular Research, Research Institute of Enviromental Medicine, Nagoya Universit

• Suzuki Tomoyuki

  Department of Cardiovascular Research, Research Institute of Enviromental Medicine, Nagoya Universit

• Opthof Tobias

  Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, The Nethe

• 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

• Takagishi Yoshiko

  Department Of Teratology And Genetics Division Of Molecular And Cellular Adaptation Research Institu

• Opthof Tobias

  Experimental And Molecular Cardiology Groups Academic Medical Center

• Kamiya Kaichiro

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Harada Masahide

  Department Of Cardiology Tokyo Medical University

• Kodama Itsuo

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

• Hibino Takenori

  Department Of Circulation Research Institute Of Environmental Medicine Nagoya University

• 本荘 晴朗

  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

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