Salidroside Mitigates Malignant Arrhythmias by Restoring Sodium Channel Function During Ultra-Acute Myocardial Infarction

Abstract Background The ultra-acute phase (Phase 1a) of acute myocardial infarction (AMI) is marked by a high incidence of malignant arrhythmias, often occurring during the prehospital period. Currently, there are no effective treatment options available for managing these arrhythmias at this early stage. Methods and Results Using dual-channel optical mapping, we simultaneously recorded membrane potentials and calcium transients during acute myocardial infarction. Calcium transient duration maps accurately localized the infarcted region, and action potential activation time maps revealed conduction heterogeneity in the infarcted zone. Patch-clamp recordings showed that Salidroside (Sal) (1 µg/mL) significantly increased sodium current density from -59.27 ± 2.15 pA/pF to -83.46 ± 3.19 pA/pF (P<0.01) and shifted the Nav1.5 activation curve leftward (V1/2 from -37.27 ± 0.5 mV to -44.55 ± 0.7 mV, P<0.01). In rat and rabbit AMI models, Sal pre-treatment reduced conduction heterogeneity and arrhythmia incidence compared to controls. Optical mapping showed improved conduction velocity and uniformity in the Sal group. Conclusions Sal restores electrophysiological function in damaged myocardium by modulating sodium currents, reducing conduction heterogeneity, and decreasing malignant arrhythmia incidence during the ultra-acute phase of AMI. These findings suggest a novel therapeutic strategy for AMI, addressing a critical unmet need in antiarrhythmic therapy. What is New? This study identifies Salidroside (Sal) as a novel agent that enhances sodium channel currents (Nav1.5), distinguishing it from traditional antiarrhythmic drugs which primarily target potassium channels or β-adrenergic receptors. Sal improves conduction uniformity in the infarcted myocardium by restoring the electrophysiological function of damaged cardiac cells, eliminating slow conduction pathways, and reducing conduction heterogeneity. This research introduces Sal as a promising candidate for preventing and treating arrhythmias during the critical early stages of MI, potentially improving patient outcomes. Sal administration during the ultra-acute phase (phase 1a) of myocardial infarction (MI) significantly reduces the incidence of malignant arrhythmias, a critical period characterized by high extracellular potassium and increased arrhythmia risk. Utilizing calcium transient imaging and optical mapping, this study provides precise localization of ischemic regions and detailed electrophysiological characterization, offering a robust methodology for assessing therapeutic efficacy.