Ganglionated plexi (GP), consisting of conglomerations of autonomic ganglia on the epicardial surface of the heart, have been shown to play a significant role in different arrhythmias, including atrial fibrillation. GP ablation has become an adjunctive procedure in the treatment of atrial fibrillation, while it has been used successfully in preliminary studies in vasovagal syncope. This review will present the current data on the physiology and clinical applications of GP ablation in the treatment of atrial fibrillation and other diseases.
Background—Prior studies indicated that ablation of the 4 major atrial ganglionated plexi (GP) suppressed atrial fibrillation.
Methods and Results—Superparamagnetic nanoparticles (MNPs) made of Fe3O4 (core), thermoresponsive polymeric hydrogel (shell), and neurotoxic agent (N-isopropylacrylamide monomer [NIPA-M]) were synthesized. In 23 dogs, a right thoracotomy exposed the anterior right GP (ARGP) and inferior right GP (IRGP). The sinus rate and ventricular rate slowing responses to high-frequency stimulation (20 Hz, 0.1 ms) were used as the surrogate for the ARGP and IRGP functions, respectively. In 6 dogs, MNPs carrying 0.4 mg NIPA-M were injected into the ARGP. In 4 other dogs, a cylindrical magnet (2600 G) was placed epicardially on the IRGP. MNPs carrying 0.8 mg NIPA-M were then infused into the circumflex artery supplying the IRGP. The hydrogel shell reliably contracted in vitro at temperatures 37°C, releasing NIPA-M. MNPs injected into the ARGP suppressed high-frequency stimulation–induced sinus rate slowing response (408% at baseline; 219% at 2 hours; P0.006). The lowest voltage of ARGP high-frequency stimulation inducing atrial fibrillation was increased from 5.90.8 V (baseline) to 10.20.9 V (2 hours; P0.009). Intracoronary infusion of MNPs suppressed the IRGP but not ARGP function (ventricular rate slowing: 578% at baseline, 208% at 2 hours; P0.002; sinus rate slowing: 317% at baseline, 338% at 2 hours; P0.604). Prussian Blue staining revealed MNP aggregates only in the IRGP, not the ARGP.
Conclusions—Intravascularly administered MNPs carrying NIPA-M can be magnetically targeted to the IRGP and reduce GP activity presumably by the subsequent release of NIPA-M. This novel targeted drug delivery system can be used intravascularly for targeted autonomic denervation. (Circulation. 2010;122:2653-2659.)