Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction.

Dongze Zhang,Chaojun Wang,Michael C Wadman,Liang Cao,Robert L Muelleman,Huiyin Tu,Yu-Long Li

doi:10.3389/fnins.2017.00252

Abstract

Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca2+ currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG neurons with ventricular arrhythmogenesis in CHF rats.Methods and Results: CHF was induced in male Sprague-Dawley rats by surgical ligation of the left coronary artery. The data from 24-h continuous radiotelemetry ECG recording in conscious rats showed that ventricular tachycardia/fibrillation (VT/VF) occurred in 3 and 14-week CHF rats but not 8-week CHF rats. Additionally, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in 14-week CHF rats but not 3 or 8-week CHF rats. Results from whole-cell patch clamp recording demonstrated that N-type Ca2+ currents in AVG neurons began to decrease in 8-week CHF rats, and that there was also a significant decrease in 14-week CHF rats. Correlation analysis revealed that N-type Ca2+ currents in AVG neurons negatively correlated with the cumulative duration of VT/VF in 14-week CHF rats, whereas there was no correlation between N-type Ca2+ currents in AVG neurons and the cumulative duration of VT/VF in 3-week CHF.Conclusion: Malignant ventricular arrhythmias mainly occur in the early and late stages of CHF. Electrical remodeling of AVG neurons highly correlates with the occurrence of ventricular arrhythmias in the late stage of CHF.

Highlights

Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF)
There was no significant difference in mean arterial pressure (MAP) between age-matched sham and CHF rats (Table 1)
As the index of left ventricular contractility, left ventricular systolic pressure (LVSP) and LV dP/dtmax were gradually decreased from the early stage (3 weeks after Myocardial infarction (MI), 3-week CHF) to the late stage of CHF rats (14 weeks after MI, 14-week CHF), compared with age matched sham rats (p < 0.05 vs. age-matched sham rats)

Summary

Introduction

Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca2+ currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Ventricular arrhythmia, including ventricular tachycardia and ventricular fibrillation (VT/VF), is the most common cause of sudden cardiac death (SCD) in patients with chronic heart failure (CHF) (Tomaselli and Zipes, 2004; Kolettis et al, 2015). Our recent study demonstrates that N-type Ca2+ currents and cell excitability of intracardiac ganglionic neurons are reduced in the late stage of CHF rats (Tu et al, 2014). The ventricular myocardium only receives projection of nerve terminals from the AVG (Pardini et al, 1987) These facts indicate that neuronal remodeling of the AVG is possibly involved in ventricular arrhythmogenesis in the CHF state

Results

Discussion

Conclusion