Tragus Nerve Stimulation Suppresses Post-Infarction Ventricular Arrhythmia by Modulating Autonomic Activity and Heterogeneities of Cardiac Receptor Distribution.

BACKGROUND Imbalanced cardiac autonomic control and cardiac receptors redistribution contribute to the arrhythmogenic substrate under the myocardial infarction (MI) condition. Stimulating the auricular branch of vagus nerve (AB-VNS) has been proven to reduce post-infarction ventricular arrhythmia (VAs), but its potential mechanisms were largely unknown. This study aimed to investigate whether long-term intermittent low-intensity AB-VNS could produce a protective effect on modulating autonomic activities and abnormal redistribution of autonomic nerve efferent receptors in a MI canine model. MATERIAL AND METHODS Twelve healthy beagle dogs underwent ligation of the left anterior descending coronary artery to establish a MI model and were randomized into 2 groups: an AB-VNS group, (AB-VNS for 4 weeks) and a control group (sham stimulation for 4 weeks). Dynamic electrocardiogram recording, neural recording, catecholamine concentration, and histological studies were conducted subsequently. RESULTS Compared to the control group, the AB-VNS group had significantly suppressed post-infarction VAs, reduced low frequency (LF) power and increased high frequency (HF) power. In the AB-VNS group, with the progression of reduced cardiac sympathetic activities and augmented cardiac parasympathetic activities, the catecholamine concentration in heart tissue declined in the peripheral infarction area and right ventricle (RV); tyrosine hydroxylase (TH)-positive neurons decreased in the inferior cardiac sympathetic nerve, and choline acetyltransferase (ChAT)-positive neurons increased in the cervical vagus nerve. Expression of TrkA and P75NGFR were reduced in the peripheral MI (peri-MI) and non-MI area with AB-VNS. The mRNA expression of adrenergic and nicotinic receptors (ß1-AR, ß3-AR, and CHRNA7) significantly declined in the peri-MI and non-MI area of the AB-VNS group. CONCLUSIONS Chronic intermittent low-intensity AB-VNS effectively suppressed post-infarction VAs by potentially rebalancing extracardiac intrathoracic autonomic activities, reducing excessive cardiac sympathetic denervation, and attenuating the heterogeneities of cardiac efferent nerve receptors distribution.

Renal Sympathetic Denervation Improves Outcomes in a Canine Myocardial Infarction Model.

BACKGROUND Myocardial infarction (MI) is the main cause of heart failure (HF), and sympathetic nerve activity is associated with prognosis chronic heart failure. Renal sympathetic denervation (RDN) is noted for its powerful effect on the inhibition of sympathetic nerve activity. This study investigated the effect of RDN on heart failure in dogs after myocardial infarction. MATERIAL AND METHODS The experimental animals were randomized into 2 groups: the MI group (n=12) and the sham operation group (n=6). In the MI group we established an MI model by permanently ligating the left anterior descending branch. After 4 weeks, the MI dogs were randomly divided into 2 groups: the MI+RDN group (MI+renal sympathetic denervation, n=6) and the simple MI group (n=6). Animals in the MI+RDN group underwent both surgical and chemical renal denervation. RESULTS Compared with sham operation group, left ventricular fraction shortening (LVFS) and left ventricular ejection fraction (LVEF) were significantly reduced in the simple MI group, while the reduction was partly reversed in the MI+RDN group. RDN reduced sympathetic nerve activity and release of B-type natriuretic peptide (BNP) and Angiotensin II (AngII) in the MI+ RDN group but not in the simple MI group. CONCLUSIONS Canine renal sympathetic denervation prevents myocardial malignant remodeling by lowering the activity of the systemic sympathetic nerve and inhibiting renin-angiotensin-aldosterone system (RASS) activation, providing a new target and method for the treatment of heart failure.

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.