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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15-26
Number of pages12
JournalJournal of Pharmacological Sciences
Volume115
Issue number1
DOIs
Publication statusPublished - 14-03-2011

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Bepridil
Myocardium
Action Potentials
Ventricular Tachycardia
Cardiac Myocytes
Tachycardia
Atrial Fibrillation
Coloring Agents

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Takanari, Hiroki ; Honjo, Haruo ; Takemoto, Yoshio ; Suzuki, Tomoyuki ; Kato, Sara ; Harada, Masahide ; Okuno, Yusuke ; Ashihara, Takashi ; Opthof, Tobias ; Sakuma, Ichiro ; Kamiya, Kaichiro ; Kodama, Itsuo. / Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling. In: Journal of Pharmacological Sciences. 2011 ; Vol. 115, No. 1. pp. 15-26.
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Takanari, H, Honjo, H, Takemoto, Y, Suzuki, T, Kato, S, Harada, M, Okuno, Y, Ashihara, T, Opthof, T, Sakuma, I, Kamiya, K & Kodama, I 2011, 'Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling', Journal of Pharmacological Sciences, vol. 115, no. 1, pp. 15-26. https://doi.org/10.1254/jphs.10233FP

Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling. / Takanari, Hiroki; Honjo, Haruo; Takemoto, Yoshio; Suzuki, Tomoyuki; Kato, Sara; Harada, Masahide; Okuno, Yusuke; Ashihara, Takashi; Opthof, Tobias; Sakuma, Ichiro; Kamiya, Kaichiro; Kodama, Itsuo.

In: Journal of Pharmacological Sciences, Vol. 115, No. 1, 14.03.2011, p. 15-26.

Research output: Contribution to journalArticle

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T1 - Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling

AU - Takanari, Hiroki

AU - Honjo, Haruo

AU - Takemoto, Yoshio

AU - Suzuki, Tomoyuki

AU - Kato, Sara

AU - Harada, Masahide

AU - Okuno, Yusuke

AU - Ashihara, Takashi

AU - Opthof, Tobias

AU - Sakuma, Ichiro

AU - Kamiya, Kaichiro

AU - Kodama, Itsuo

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N2 - 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.

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