Open-chest Pulsed Electric Field Ablation of Cardiac Ganglionated Plexi in Acute Canine Models

Abstract

This study aimed to evaluate the safety and acute effect on markers of cardiac autonomic tone following pulsed electric fields (PEFs) delivered to epicardial ganglionated plexi (GP) during a cardiac surgical procedure. Ablation of GP as a treatment for atrial fibrillation (AF) has shown promise, but thermal ablation energy sources are limited by the risk of inadvertent collateral tissue injury. In acute canine experiments, median sternotomy was performed to facilitate the identification of 5 epicardial GP regions using an anatomy-guided approach. Each site was targeted with saline-irrigated PEF (1000 V, 100 μs, 10 electrocardiogram [ECG]-synchronized pulse sequences). Atrial effective refractory period (AERP) and local electrogram (EGM) amplitude were measured before and after each treatment. Histology was performed on samples from treatment-adjacent structures. In 5 animals, 30 (n = 2) and 60 (n = 3) pulses were successfully delivered to each of the 5 target sites. There was no difference in local atrial EGM amplitude before and after PEF application at each site (1.83 ± 0.41 vs. 1.92 ± 0.53 mV, P = .72). The mean AERP increased from 97 ± 15 ms at baseline to 115 ± 7 ms following treatment at all sites (18.6% increase; 95% confidence interval, 1.9-35.2; P = .037). There were no sustained ventricular arrhythmias or acute evidence of ischemia following delivery. Histology showed complete preservation of adjacent atrial myocardium, phrenic nerves, pericardium, and esophagus. Use of PEF to target regions rich in cardiac GP in open-chest canine experiments was feasible and effective at acutely altering markers of cardiac autonomic tone.

Keywords: Ganglionated plexi; atrial fibrillation; cardiac denervation; electroporation; pulsed electric fields.

Figure 1:

Target anatomical regions known to be rich in clinically important ganglionated plexi. Ganglionated plexi (yellow dots) with roles important to initiation or maintenance of AF were targeted with pulsed electric field delivery through an open-chest anatomic approach. Abbreviations: LMGP, ligament of Marshall ganglionated plexi; LSGP, left superior ganglionated plexi; OSGP, oblique sinus ganglionated plexi; RSGP, right superior ganglionated plexi; TSGP, transverse sinus ganglionated plexi.

Figure 2:

Catheters and pulsed electric field generator. A: AtriAN catheters used for pulsed electric field with 2 different tip elements designed to reach target treatment sites. B: AtriAN PEFG01 pulsed electric field generator.

Figure 3:

Transient atrial current of injury. Electrograms recorded from the energy delivery catheters at baseline, immediately following delivery, and after a 10-min delay in a representative animal (#3). Note the transient atrial injury current (yellow arrow) between atrial and ventricular potentials on the local unipolar electrogram followed by recovery of signal amplitude and morphology to approximate baseline. Abbreviations: LMGP, ligament of Marshall ganglionated plexi; LSGP, left superior ganglionated plexi; OSGP, oblique sinus ganglionated plexi; RSGP, right superior ganglionated plexi; TSGP, transverse sinus ganglionated plexi.

Figure 4:

Pre- and post-treatment AERP analysis. AERP stratified per animal and combined overall before and after pulsed electric field delivery to all target sites with t test estimation plot. Abbreviation: AERP, atrial effective refractory period.

Figure 5:

Treatment site histology. Histology of an atrial section at the treated oblique sinus ganglionated plexus region in animal #4 prepared with hematoxylin and eosin (A) as well as Masson’s trichome (B) stains. Nerve fibers (N) and a ganglion (G) are shown within epicardial fat adjacent to atrial myocardium (M). Tissue architecture is preserved without cellular disarray or nuclear disintegration.