Introduction
Heart failure (HF) and arrhythmia share a similar underlying pathogenesis, such as an autonomic imbalance, atrial or ventricular electrical remodeling, and inflammatory reactions [1]. In humans, tachycardia-induced cardiomyopathy often leads to HF,which includes atrial fibrillation (AF), incessant supraventricular tachycardia, frequent ventricular ectopy, and ventricular tachycardia[2]. Traditional pharmacologic therapy does not appear to be efficacious at treating this type of HF. Even the relatively new resynchronization therapy is not as effective in arrhythmic patients. Therefore, a new method eagerly awaited in clinical practice. As autonomic remodeling and inflammation are associated with the initiation and maintenance of HF and AF, suppressing the activity of both elements has been widely debated. Since the ventricle plays a more important role than the atrium when assessing heart function, the modulation of ventricular ganglionated plexi (GP) is thought to be better than atrial GP in promoting heart function. However, aortic root ventricular GP (ARVGP), influences the function of both the ventricle and coronary artery [3]. In addition, a previous study [4] demonstrated that low-level electrical stimulation (LL-ES) of ARVGP also affected the activity of the atrium. In this study, LL-ES attenuated and balanced the tone of the autonomic nervous system (ANS) and thus lessened the inducing rate of AF mediated by the ANS. If LL-ES of ARVGP also shows short-term effects and has an anti-inflammatory effect on the ventricle, it is plausible to expect that it may benefit both HF and arrhythmia.
Therefore, the present study established a tachycardia-induced HF model by rapid pacing. One week (w) of short-term LL-ES of ARVGP was performed, which was followed by programmed/burst electrical stimulation, immunohistochemical assays, polymerase chain reaction, and Western blotting to investigate the following: (1) the inducing rates of both atrial and ventricular arrhythmia to determine if LL-ES of ARVGP reduces arrhythmic episodes; (2) bioactive factors of HF, such as angiotensin II, transforming growth factor-beta (TGF-β), mitogen-activated protein kinase (MAPK), and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) to explore whether LL-ES of ARVGP suppresses the inflammatory reaction; and (3) the ventricular effective refractory period (VERP),the left ventricular end-diastolic volume(LVEDV) and end-systolic volume(LVESV),the stroke volume of the left ventricle (LVSV), and the left ventricular ejection fraction (LVEF) to demonstrate whether LL-ES of ARVGP contributes to improving heart function.

Material and Methods

Creation of an HF model

This study conforms to the Guide for the Care and Use of Laboratory Animals. All animal protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the Jiao Tong University (Xi’an, China).
HF was induced by rapid ventricular pacing to simulate tachycardia-induced cardiomyopathy, as described by Armstrong et al. [5]. Thirty dogs were anesthetized with an IV injection of 3% sodium pentobarbital (30 mg/kg). An extradose was given to maintain anesthesia during this study, if necessary.Five percent glucose in normal saline (500 mL) with penicillin was administered intravenously. An endocardial pacemaker electrode (St. Jude Medical, MN, USA) was inserted using fluoroscopy into the right ventricular apex via the left external jugular vein. A pacemaker generator was implanted into a small subcutaneous pocket created between the scapulas, and the pacemaker lead was connected to the generator through a subcutaneous canal. The pacing threshold was 0.3-1.5 V, the amplitude of the R-wave was 4-10 mV, and the impedance was 0.3-1.0 KΩ. The pacemaker frequency was set at 240 beats per minute with an output voltage of 5.0 V and a pulse width of 0.5 ms one week (w) after the initiation of rapid pacing. An echocardiography and cardiac ultrasound were performed twice with an interval of 24 h to confirm the presence of stable congestive HF. Then, the pacing electrode was extracted.