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.