Renal Nerve Stimulation and Ventricular Arrhythmia

Abstract and Introduction

Abstract

Renal Sympathetic Nerves and Ventricular Arrhythmias. Introduction Renal sympathetic nerve (RSN) activity plays a key role in systemic sympathetic hyperactivity. Previous studies have shown that cardiac sympathetic hyperactivity, especially the left stellate ganglion (LSG), contributes to the pathogenesis of ventricular arrhythmias (VAs) after acute myocardial infarction (AMI).

Methods and Results Twenty-eight dogs received 3 hours of continuous left-sided electrical stimulation of RSN (LRS; Group-1, n = 9), sham RSN stimulation (Group-2, n = 9), or LSG ablation plus 3 hours of LRS (Group-3, n = 10) were included. AMI was induced by ligating the proximal left anterior descending coronary artery. LRS was performed using electrical stimulation on the adventitia of left renal artery at the voltage increasing the systolic blood pressure (BP) by 10%. BP, heart rate variability (HRV), serum norepinephrine (NE) level, and LSG function were measured at baseline and the end of each hour of LRS. C-fos and nerve growth factor (NGF) protein expressed in the LSG were examined in Group-1 and Group-2. Compared with baseline, 3 hours of LRS induced a significant increase in BP, sympathetic indices of HRV, serum NE level, and LSG function. The incidence of VAs in Group-1 was significantly higher than other groups. The expression of c-fos and NGF protein in the LSG was significantly higher in Group-1 than Group-2.

Conclusion Three hours of LRS induces both systemic and cardiac sympathetic hyperactivity and increases the incidence of ischemia-induced VAs.

Introduction

Ventricular arrhythmias (VAs) represent a major cause of sudden cardiac death (SCD) in myocardial infarction (MI).^[1,2] It is well accepted that hyperactivity of the cardiac sympathetic nervous system, especially the left stellate ganglion (LSG), contributes to the pathogenesis of VAs and SCD.^[3–5] Histological studies of human hearts suggest that increased sympathetic nerves density is closely related to the incidence of life-threatening VAs.^[3] Infusion of nerve growth factor (NGF) or applying long-term electrical stimulation to the LSG induces cardiac sympathetic hyperinnervation and increases the susceptibility to VAs in dogs with complete atrioventricular block and MI.^[4,5]

Renal sympathetic nerve (RSN) has been shown to be an important mediator of systemic sympathetic tone.^[6] Several studies have demonstrated that RSN denervation can reduce whole body sympathetic activity^[7] and have therapeutic value in syndromes associated with systemic sympathetic hyperactivity.^[8,9] Recently, Hoffmann et al.^[10] reported a case of drug-refractory ventricular storm in a patient with acute ST-elevation MI, in which percutaneous RSN denervation was performed. The frequency of ventricular tachycardia (VT) or ventricular fibrillation (VF) episodes decreased after RSN denervation and eventually dissipated. Putting these observations together, we hypothesized that RSN may be a major contributor to cardiac sympathetic activation and the generation of VAs after acute MI (AMI). We tested the hypothesis by delivering continuous, high-frequency stimulation (HFS) to the left RSN (LRS) for 3 hours. We measured the systemic blood pressure (BP), heart rate (HR), heart rate variability (HRV), serum norepinephrine (NE), LSG function, incidence of VAs, as well as the expression of c-fos and NGF in the LSG before and after AMI.