Long-Term Effects of Ganglionated Plexi Ablation on Electrophysiological Characteristics and Neuron Remodeling in Target Atrial Tissues in a Canine Model

Abstract

Background-The long-term effects of ganglionated plexi ablation on electrophysiological characteristics and neuron remodeling in target atrial tissues remain unclear. Methods and Results-Dogs in group 1 (control, n=8) were not subjected to ganglionated plexi ablation and observed for 1 month, and dogs in groups 2 to 4 (ablation groups, n=8 each) underwent ablation of the right-sided ganglionated plexi and observed for 1, 6, and 12 months, respectively. Atrial electrophysiological characteristics were examined before ablation, immediately and continuously after ablation. Target atrial tissues were subjected to immunohistochemical staining and Western blot analysis. Atrial effective refractory period was significantly prolonged immediately after ablation (P<0.001), and persisted for 1 month (P<0.05). Nerve densities decreased 1 month after ablation (P<0.001). These parameters reverted to preablation levels after 6 and 12 months. In the ablation groups, atrial fibrillation was induced in 5 of 8 dogs after 1 month and in all animals after 6 and 12 months. Atrial fibrillation was not observed in the control group and in the experimental groups immediately after ablation. Moreover, the expression of the growth-associated protein 43 was upregulated after ablation. Conclusions-Ganglionated plexi ablation effectively prolonged atrial effective refractory period for a short period, but the long-term effects on atrial effective refractory period and the suppression of atrial fibrillation induction were not persistent. Targeted atrial neuron remodeling may be an important mechanism underlying the observed electrophysiological changes.

Epicardial ganglionated plexi ablation increases the inducibility of ventricular tachyarrhythmias in a canine postmyocardial infarction model

“…In structurally normal animal hearts, acute EGPA retains sinoatrial and atrioventricular nodal functions, and does not increase the inducibility of ventricular arrhythmia . Recently, Mao et al and Wang et al investigated the long‐term effects of EGPA on atrial/ventricular electrophysiological properties and sinoatrial/atrioventricular node function in noninfarcted canines. Mao et al found that systematic EGPA significantly decreased atrial ERP, increased the inducibility of atrial tachyarrhythmias and the density of TH‐ and ChAT‐positive nerves in the atrium at an 8‐week follow‐up.…”

Ablation of Ganglionated Plexi in the Long Term

“…25 Indeed, a recent clinical report detailed previously unrecognized focal firing sources in the left atrial appendage found in 27% of patients having repeat procedures whose AF was successfully ablated by targeting these sites. 26 (2) The unexpected increase in heart rate reported by Wang et al 1 and others 5 could be because of increased sympathetic innervation from the right stellate ganglion, which ordinarily connects to the sinus node via the anterior right GP. With the ablation of the latter, neural plasticity and nerve growth of the interganglionic nerve, which bypasses the GP 27 can directly affect the sinus node to cause the persistent increased heart rate.…”

“…Assuming that there is no damage to nerve cell bodies, such as exist within the atrial neural network after major GP ablation, nerve sprouts can emerge from each parent axon, thereby increasing the total number of axons exceeding the number of parents. 24 The GP ablation studies of Wang et al 1 and the experimental and clinical studies of others have shown: (1) autonomic remodeling in the form of neural plasticity comes from Scherlag Editorial Based on X. Wang et alwithin the atrial neural network in the form of nerve sprouting, reversal of AERP prolongation and rotor and focal source origins of AF initiation and maintenance. 25 Indeed, a recent clinical report detailed previously unrecognized focal firing sources in the left atrial appendage found in 27% of patients having repeat procedures whose AF was successfully ablated by targeting these sites.…”

“…I n this issue of Circulation: Arrhythmia and Electrophysiology, Wang et al 1 demonstrated, in the dog heart, that ablation of the right-sided ganglionated plexi (GP) whose axons innervate the sinoatrial and atrioventricular nodes 2 acutely induced significant prolongation of atrial effective refractory period (AERP) but in the long term these effects were reversed. Moreover, nerve density of parasympathetic and sympathetic nerves was markedly increased after GP ablation.…”

Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation

“…Interestingly, AF was more inducible in the treatment group compared to the control group at 6 and 12 months. (Wang et al, 2015) A second study targeting the epicardial ganglionated plexi in dogs similarly showed an increase in atrial arrhythmias, which was attributed to an overall decrease in the atrial effective refractory period and hyper-reinnervation of both the sympathetic and parasympathetic nerves. (Mao et al, 2014) By contrast, the sinus node seems to have the capability to remodel electrically after AF ablation, and has shown the potential to improve to normal function.…”