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

Journal of Pharmacological Sciences

Hiroki Takanari¹  Sara Kato¹  Ichiro Sakuma²  Tobias Opthof⁴  Yusuke Okuno¹  Yoshio Takemoto¹  Tomoyuki Suzuki¹  Haruo Honjo¹  Itsuo Kodama¹  Kaichiro Kamiya¹  Masahide Harada¹  Takashi Ashihara³ 

[1] Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan;Graduate School of Engineering, The University of Tokyo, Japan;Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Japan;Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, The Netherlands

关键词: bepridil;    spiral-wave reentry;    intercellular coupling;    optical mapping;    ventricular tachycardia;   

DOI  :  10.1254/jphs.10233FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(40)Cited-By(5)Supplementary materials(1)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]

【 授权许可】

Unknown