title: Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling.
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.
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takanari
authors.forename: Haruo
authors.initials: H
authors.lastname: Honjo
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Sara
authors.initials: S
authors.lastname: Kato
authors.forename: Masahide
authors.initials: M
authors.lastname: Harada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuno
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashihara
authors.forename: Tobias
authors.initials: T
authors.lastname: Opthof
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015764:Bepridil / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000502:physiology; D011817:Rabbits; D051381:Rats; D013268:Stimulation, Chemical; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D015764:Bepridil