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

Hiroki Takanari; Haruo Honjo; Yoshio Takemoto; Tomoyuki Suzuki; Sara Kato; Masahide Harada; Yusuke Okuno; Takashi Ashihara; Tobias Opthof; Ichiro Sakuma; Kaichiro Kamiya; Itsuo Kodama

doi:10.1254/jphs.10233FP

Full Papers

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

Hiroki Takanari, Haruo Honjo, Yoshio Takemoto, Tomoyuki Suzuki, Sara Kato, Masahide Harada, Yusuke Okuno, Takashi Ashihara, Tobias Opthof, Ichiro Sakuma, Kaichiro Kamiya, Itsuo Kodama

Author information

Hiroki Takanari
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan
Haruo Honjo
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan
Yoshio Takemoto
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan
Tomoyuki Suzuki
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan
Sara Kato
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan
Masahide Harada
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan
Yusuke Okuno
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan
Takashi Ashihara
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Japan
Tobias Opthof
Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, The Netherlands
Department of Medical Physiology, University of Utrecht, The Netherlands
Ichiro Sakuma
Graduate School of Engineering, The University of Tokyo, Japan
Kaichiro Kamiya
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan
Itsuo Kodama
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan

Keywords: bepridil, spiral-wave reentry, intercellular coupling, optical mapping, ventricular tachycardia

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Supplementary material

2011 Volume 115 Issue 1 Pages 15-26

DOI https://doi.org/10.1254/jphs.10233FP

View "Advance Publication" version (December 9, 2010).

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Abstract

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]

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