Discussion
The main findings of this study were that short-term LL-ES of ARVGP provided both anti-arrhythmia and anti-inflammation benefits, and therefore improved cardiac function in the short-term. In addition, compared to the drug group, TGF-β, MMP-9, and AT-1R protein levels in the LV decreased significantly after LL-ES, whereas p-ERK1/2 levels significantly increased. It is well known that the p-ERK signaling pathway is a protein kinase subfamily in the heart that provides a protective effect. Other subfamilies include the p38 and jun N-terminal kinases, which may play an opposite role in the heart. For this reason, they were not chosen for examination in this study. This study demonstrated that p-ERK could be activated by LL-ES, which suggests that LL-ES of ARVGP may play a protective role for the heart through the p-ERK signaling pathway.
Although TGF-β, MMP-9, and AT-1R protein levels reduced significantly after 1w of traditional drug administration compared with the control group, it did not improve heart function as well as expected. This conformed to the present clinical status that traditional drugs showed an obvious limitation in the treatment of tachycardia-induced HF. However, 12 h of immediate LL-ES did not promote heart function well because 1w of tachycardia-induced HF resulted in relatively persistent electrical remodeling, which was hard to reverse in such a short time.
Increased sympathetic nerve activity and reduced vagal cardiac tone have been demonstrated to be pathogenic in HF or AF [9]. With the shortening of VERP following an imbalanced ANS tone, premature ventricular beats or tachycardia can occur easily and thus facilitate HF[10].However, our results demonstrated a prolongation of VERP and rebalancing of ANS tone. As a result, episodes of ventricular arrhythmia decreased after LL-ES of ARVGP. In addition, an inflammatory reaction is involved in both the initiation and maintenance of HF and AF [11]. Therefore, current practices are expected to improve both HF and arrhythmia by reversing the imbalanced tone of the ANS and inhibiting the activity of inflammatory factors.
Vagal nerve electrical stimulation has been widely used to control HF and AF [12, 13]. Side effects commonly include neck pain, coughing, difficulty in swallowing, voice alteration, nausea, and indigestion, which limit the application of vagal nerve modification [14]. Recently, several studies demonstrated that LL-ES of local atrial GP was effective in suppressing AF and inflammatory reactions [15, 16]. However, our study demonstrated that LL-ES of ARVGP also resulted in anti-arrhythmia and anti-inflammation effects that were restricted to the heart, thus avoiding the side effects of vagal nerve stimulation. Moreover, 1 w of LL-ES improved the LVEF, reduced LV size, and reversed the acute structural and electrical remodeling of the heart. As a result, the electrical remodeling caused by rapid pacing was reversed. A potential mechanism for these effects lies in the significant suppression of stellate ganglion nerve activity and sympathetic nerve density [17]. In conclusion, short-term LL-ES of ARVGP may be a better choice than traditional drugs for treating tachycardia-induced HF and associated arrhythmia.