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.