Shensong yangxin reduces transmural dispersion of repolarisation and prevents ventricular arrhythmias in an ex-vivo model of Brugada syndrome
N Yoon, S N HongAbstract
Background
Shensong Yangxin (SSYX), a multi-component traditional Chinese medicine, has been reported to inhibit multiple cardiac ion channels, including the transient outward potassium current (Ito), which plays an important role in the pathophysiology of Brugada syndrome (BrS). However, its potential antiarrhythmic effects in BrS have not been systematically investigated.
Purpose
This study aimed to evaluate the electrophysiological and antiarrhythmic effects of SSYX in an established ex vivo canine model of BrS.
Methods
Coronary-perfused canine right ventricular wedge preparations were used to simultaneously record transmembrane action potentials (APs) and pseudo-electrocardiograms. The electrophysiological effects of SSYX were first assessed under baseline (non-BrS) conditions. BrS phenotype was subsequently induced using acetylcholine, verapamil, and the Ito agonist NS5806. The effects of SSYX on action potential morphology, transmural dispersion of repolarization (TDR), J-wave characteristics, and ventricular arrhythmogenesis were analyzed.
Results
Under baseline conditions, SSYX (10 mg/dL) significantly reduced TDR, AP notch magnitude, and J-wave area. SSYX produced dose-dependent prolongation of action potential duration (APD) and attenuation of phase 1 repolarization. In BrS preparations, SSYX (10 mg/dL) reduced phase 1 repolarization and completely suppressed ventricular tachyarrhythmias. SSYX significantly reduced TDR (26.15±0.42 ms to 9.54±0.24 ms, p<0.001), AP notch magnitude (37.73±1.69% to 1.61±0.14%, p<0.001), and J-wave area (24.24±0.61 mV·ms to 1.76±0.21 mV·ms, p<0.001).
Conclusions
SSYX demonstrated antiarrhythmic effects in this experimental BrS model by restoring the action potential dome, reducing J-wave amplitude, and normalizing transmural repolarization gradients, resulting in suppression of ventricular tachyarrhythmias. These findings suggest that multi-ion channel modulation with SSYX may represent a novel pharmacological strategy for ventricular arrhythmia prevention in BrS, warranting further translational and clinical investigation.VT suppressionChange of TDR