Ablation of Epicardial Ganglionated Plexi Increases Atrial Vulnerability to Arrhythmias in Dogs

Abstract

Background-Previous studies have suggested that systematic ablation of ganglionated plexi (GP) could increase the shortterm success rate of radiofrequency ablation for atrial fibrillation, but the long-term efficacy of this approach is not fully established. Methods and Results-Twenty-four mongrel dogs were divided into 3 groups: epicardial GP ablation group 1 (n=8), epicardial GP ablation group 2 (n=8), and a sham operation group (n=8). In the 2 epicardial GP ablation groups, the 4 major GP and the ligament of Marshall were systematically ablated. The effective refractory period and inducibility of tachyarrhythmias were measured before and immediately after GP ablation in epicardial GP ablation group 1 and 8 weeks later in the other 2 groups. Tyrosine hydroxylase and choline acetyltransferase expressions were also determined immunohistochemically 8 weeks later in the latter groups. Compared with epicardial GP ablation group 1 and the sham operation group, epicardial GP ablation group 2 had the shortest atrial and ventricular effective refractory period and the highest inducibility of atrial tachyarrhythmias. The inducibility of ventricular tachyarrhythmias among the 3 groups was comparable. The density of tyrosine hydroxylase-and choline acetyltransferase-positive nerves in the atrium was the highest in epicardial GP group 2, whereas there were no significant intergroup differences in the densities of these 2 types of nerves in the ventricle. Conclusions-After 8 weeks of healing, epicardial GP ablation without additional atrial ablation was potentially proarrhythmic, which may be attributable to decreased atrial effective refractory period and hyper-reinnervation involving both sympathetic and parasympathetic nerves. Methods Animal PreparationAll animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at our institution. Twenty-four adult mongrel dogs (18-25 kg) were divided into 3 groups: epicardial GP ablation group 1 (n=8), epicardial GP ablation group 2 (n=8), and a sham operation group (n=8). All dogs were anesthetized with 5% sodium pentobarbital (2-3 mL/kg) given intravenously, followed by an additional dose of 1 mL/kg at the end of each hour. A tracheal cannula was inserted, and intermittent positive pressure ventilation with room air was delivered by a respirator. A 6-lead frontal ECG was recorded continuously during the procedure (filter, 0.05-30 Hz). After left thoracotomy at the fourth intercostal space, the heart was exposed in a pericardial cradle. GP AblationIn the 2 epicardial GP ablation groups, the LOM and the fat pads that contain the superior left GP and inferior left GP were exposed by left thoracotomy. After the superior left GP, inferior left GP, and LOM were ablated, the fat pads that contain the anterior right GP and inferior right GP were exposed by lifting up the pericardium, and the anterior right GP and inferior right GP were ablated sequentially through the left incision. The GP was localized by applying high-frequency stimulation (HFS; 20 Hz; ...

Ablation of Ganglionated Plexi in the Long Term

“…Moreover, nerve density of parasympathetic and sympathetic nerves was markedly increased after GP ablation. These findings essentially confirm previous experimental studies by Oh et al, 3 Sakamoto et al, 4 and Mao et al 5 all of whom ablated GP, and found evidence of reinnervation providing a reversal of AERP shortening and restoration of atrial fibrillation (AF) inducibility.…”

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

“…81 Autonomic signals to the heart via GP exert important electrophysiological effects including altering atrial refractory periods, 81,82 increasing the frequency of triggered atrial premature beats that can subsequently initiate AF, 83 and increasing the vulnerability of atrial tissue to the induction of AF. 81,84,85 Animal studies have demonstrated that stimulation of GP located around the pulmonary veins can reduce the number of atrial extrastimuli required to initiate AF, and that neuronal/autonomic blockade with drugs or GP ablation can prevent AF induction. 86,87 Because GP are located near the pulmonary veins, conventional PVI can often coincidently eliminate these areas, and it has been suggested that ablation of GP may help explain the success of PVI.…”

Unravelling the Paradoxical Effects of Ganglia Ablation

“…They proposed that the acute effect of a ganglionic blocker that is known to manifest hypotension acutely, in the chronic setting could result from increased vasomotor activity via a feedback mechanism or reflex loop. In the study by Mao et al, 23 the paradoxical difference between the acute and the chronic findings for atrial refractoriness and AF inducibility might reside in a similar feedback loop involving a loss of the afferent input from the GP to the vasomotor centers in the brain. During a period of time those medullary nuclei, in response to the decreased neural traffic, adjust by increasing sympathetic and parasympathetic outflow back to the intact atrial neural network.…”

“…In this issue of the journal, Mao et al 23 have reported another example of the apparently paradoxical interaction between the cardiac autonomic nervous system and AF. In a group of dogs, the major 4 GP and ligament of Marshall were ablated, whereas a comparably sized second group served as sham controls (no GP ablation).…”