Abstract Body: Background: Alongside the structural remodeling of the infarcted heart, neuronal remodeling, such as cardiac sympathetic overactivation and hyperinnervation, serves as a critical trigger for ventricular arrhythmogenesis after acute myocardial infarction (AMI). Although the therapeutic potential of renal denervation (RDN) for ventricular arrhythmias has been reported, it remains unclear if the antiarrhythmic role of RDN is achieved through attenuating AMI-induced neuronal remodeling in the stellate ganglion (SG). Since the proarrhythmic effect of the Renin-Angiotensin System (RAS) is established, our study aims to investigate whether RDN achieves its antiarrhythmic effect by mitigating Angiotensin II (Ang II)-promoted neuronal remodeling in the SG after AMI.
Methods and Results: Rat AMI was induced by surgical ligation of the left anterior descending coronary artery (LAD). Completed bilateral RDN was performed immediately after LAD ligation. Data from ELISA demonstrated that early RDN not only reduced AMI-increased renin levels in the kidney and serum but also attenuated Ang II levels in the serum and SG after AMI. Western blot and IF staining data showed that early RDN significantly decreased AMI-elevated expression of nerve growth factor (NGF) in the SG, which was accompanied by a marked improvement in AMI-induced cardiac sympathetic hyperinnervation in the border zone of the infarcted heart. More importantly, RDN immediately after AMI prevented AMI-induced cardiac sympathetic overactivation. Data from 24-hour ECG telemetry recording in conscious rats also showed that early RDN decreased the cumulative duration of ventricular tachycardia/fibrillation (VT/VF) within 14 days post-AMI. To further validate the contribution of the RAS cascade on neuronal remodeling in the SG, Ang II (1.44mg/kg/day) was subcutaneously infused into sham rats for 14 days. In addition to increasing the expression of NGF in the SG, Ang II infusion also induced cardiac sympathetic hyperinnervation and overactivation and increased the susceptibility to VT/VF in sham rats.
Conclusions: These data suggest that RDN may achieve its antiarrhythmic effect by mitigating Ang II-promoted neuronal remodeling in the SG after AMI. Targeting the RAS signaling could be a novel therapeutic strategy to achieve the antiarrhythmic effect of RDN after AMI.