Bepridil (1 μM) significantly decreased the incidence of sustained ventricular tachycardias from 34% to 6% in isolated rabbit hearts by increasing intercellular electrical coupling.
Does bepridil facilitate early termination of spiral-wave reentry in isolated cardiac muscle models?
Bepridil facilitates the early termination of spiral-wave reentry in cardiac muscle by increasing intercellular electrical coupling and moderately prolonging action potential duration.
Absolute Event Rate: 6% vs 34%
p-value: p=<0.01
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.
Takanari et al. (Thu,) conducted a other in Ventricular tachyarrhythmias (experimental model) (n=27). Bepridil vs. Control (baseline) was evaluated on Incidence of sustained ventricular tachycardias (≥60 s) per heart (p=<0.01). Bepridil (1 μM) significantly decreased the incidence of sustained ventricular tachycardias from 34% to 6% in isolated rabbit hearts by increasing intercellular electrical coupling.