Low-Level Vagus Nerve Stimulation Reverses Cardiac Dysfunction and Subcellular Calcium Handling in Rats With Post-Myocardial Infarction Heart Failure

• Published in: International Heart Journal Vol. 57; no. 3; pp. 350 - 355
• Main Authors: Zhang, Yunhe, Chen, Ao, Song, Lei, Li, Min, Luo, Zhangyuan, Zhang, Wenzan, Chen, Yingmin, He, Ben
• Format: Journal Article
• Language: English
• Published: Japan International Heart Journal Association 2016
• Subjects: Animals; Autonomic nervous system; Autonomic Nervous System - physiopathology; Calcium - metabolism; Calcium-Binding Proteins - metabolism; Disease Models, Animal; Heart Failure - etiology; Heart Failure - metabolism; Heart Failure - physiopathology; Heart Failure - therapy; Male; Myocardial Infarction - complications; Myocytes, Cardiac - metabolism; Rats; Rats, Sprague-Dawley; Ryanodine Receptor Calcium Release Channel - metabolism; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism; SERCA2a; Sodium-Calcium Exchanger - metabolism; Treatment Outcome; Vagus Nerve Stimulation - methods; Ventricular dysfunction; Ventricular Dysfunction - metabolism; Ventricular Dysfunction - physiopathology; Ventricular Dysfunction - therapy
• ISSN: 1349-2365; 1349-3299
• DOI: 10.1536/ihj.15-516

Vagus nerve stimulation (VNS), targeting the imbalanced autonomic nervous system, is a promising therapeutic approach for chronic heart failure (HF). Moreover, calcium cycling is an important part of cardiac excitation-contraction coupling (ECC), which also participates in the antiarrhythmic effects of VNS. We hypothesized that low-level VNS (LL-VNS) could improve cardiac function by regulation of intracellular calcium handling properties. The experimental HF model was established by ligation of the left anterior descending coronary artery (LAD). Thirty-two male Sprague-Dawley rats were divided into 3 groups as follows; control group (sham operated without coronary ligation, n = 10), HF-VNS group (HF rats with VNS, n = 12), and HF-SS group (HF rats with sham nerve stimulation, n = 10). After 8 weeks of treatment, LL-VNS significantly improved left ventricular ejection fraction (LVEF) and attenuated myocardial interstitial fibrosis in the HF-VNS group compared with the HF-SS group. Elevated plasma norepinephrine and dopamine, but not epinephrine, were partially reduced by LL-VNS. Additionally, LL-VNS restored the protein and mRNA levels of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), Na+–Ca2+ exchanger 1 (NCX1), and phospholamban (PLB) whereas the expression of ryanodine receptor 2 (RyR2) as well as mRNA level was unaffected. Thus, our study results suggest that the improvement of cardiac performance by LL-VNS is accompanied by the reversal of dysfunctional calcium handling properties including SERCA2a, NCX1, and PLB which may be a potential molecular mechanism of VNS for HF.