Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.

The association between carotid atherosclerosis and ischemic stroke in patients with nonvalvular atrial fibrillation / 中华内科杂志

Objective:To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF).Methods:This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke.Results:Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion:Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability.

BACKGROUND: Transcutaneous stimulation of the auricular branch of the vagus nerve (AB-VNS) is a potentially noninvasive, inexpensive, and safe approach for vagus nerve stimulation that suppresses the induction and duration of atrial fibrillation and reduces sympathetic nerve outflow in healthy humans. Researchers have not determined whether AB-VNS affects ventricular arrhythmias. OBJECTIVE: To evaluate the antiarrhythmic effects of noninvasive AB-VNS on ventricular arrhythmias induced by myocardial infarction (MI). METHODS AND RESULTS: Twelve beagle dogs were randomly divided into the following two groups: a AB-VNS group (coronary artery occlusion and noninvasive AB-VNS) and a control group (coronary artery occlusion but without AB-VNS). We examined spontaneous ventricular arrhythmias, ventricular electrophysiological properties, and cardiac function in conscious dogs. Morphology, fibrosis, and ultrastructures were also assessed. AB-VNS significantly reduced the occurrence of spontaneous ventricular arrhythmias, including isolated premature ventricular complexes, ventricular couplets, ventricular bigeminy, ventricular trigeminy, and ventricular tachycardia. AB-VNS effectively increased ventricular electrical stability, including significantly prolonged ventricular effective refractory periods, decreased the dispersion of effective refractory period, enhanced the ventricular fibrillation threshold, and decreased the maximum slope of the monophasic action potential duration restitution curve. AB-VNS treatments alleviate ventricular interstitial fibrosis after MI. However, cardiac function was not improved, and MI-induced ultrastructural changes in the myocardium were not reversed by 4 weeks of AB-VNS. In addition, AB-VNS for 4 weeks resulted in mild mitochondrial swelling within the neuronal axons of the auricular vagus fiber. CONCLUSIONS: Noninvasive AB-VNS reduces the occurrence of spontaneous ventricular arrhythmias in conscious dogs with MI. AB-VNS increases ventricular electrical stability and alleviates ventricular interstitial fibrosis induced by MI.