Unravelling the Paradoxical Effects of Ganglia Ablation

Abstract

570I n 1973, Lazzara et al 1 described 2 clusters of nerve bodies called ganglionated plexi (GP) adjacent to the sinus node and AV junction; high-frequency electric stimulation, which did not excite the underlying atrium, induced heart rate or AV conduction slowing, respectively. We are indebted to Randall et al 2 who spent the next several decades delineating the anatomy and physiology of the intrinsic cardiac autonomic nervous system consisting of GP located at several sites in the atria and ventricles. Carrying on the legacy of Dr Randall, 2 Armour and Ardell 3,4 produced numerous publications and books, providing a hierarchical construct of the neural innervation of the heart, starting at the nuclei and axonal fields in the brain (extrinsic autonomic nervous system) followed by the spinal cord (intrathoracic) ganglia and axons and their connections to the intrinsic cardiac autonomic system with its GP and their axons of passage. The last part of this interconnected chain (the atrial neural network) was delineated anatomically by Armour et al 5 and Pauza et al 6 and functionally by Hou et al. 7Article see p 711The overall function of the intrinsic autonomic nervous system consisting of the GP and the atrial neural network was summarized by Ardell,8 "… the intrinsic cardiac nerve plexus (GP and neural network) acts as more than a simple relay station for extrinsic autonomic projections to the heart…modulat-ing…extrinsic and local cardio-cardiac reflexes. The intrinsic cardiac nerve plexus contains a heterogeneous population of cell types, including parasympathetic and sympathetic efferent neurons as well as afferent neurons." Furthermore, as pointed out by Ardell, 8 these afferent neurons participate in reflex loops between and within the various levels of the extrinsic, intrathoracic, and intrinsic systems, yet each level when disconnected from the other would retain independent functionality.From 1997 to 1998, the seminal studies by Jaïs et al 9 and Haïssaguerre et al 10 showed that the myocardium of the pulmonary veins (PVs) manifested ectopic firing in patients, and this ectopy was directly associated with the initiation and maintenance of atrial fibrillation (AF). As a result, the accepted catheter ablation procedure for AF became isolation of the PVs. These findings engendered basic experimental studies demonstrating that chemical stimulation 11 of the GP at the atrial PV entrances or electric stimulation of the nerves within the PV could induce PV firing and AF. 12 Moreover, these studies specifically implicated the excessive release of both the cholinergic (marked shortening of the refractory period) and the adrenergic (induction of triggered firing) neurotransmitters as the mechanism for PV firing and ensuing AF. Clinical studies, 13,14 including surgical approaches, 15,16 have provided evidence that ablation of GP is an important adjunctive procedure to PV isolation in the treatment of AF.These clinical and recent experimental studies have provided enlightening insights into how the autonomic nervous...

Innervation of the heart: An invisible grid within a black box

“…Trials have also focused on the potential role of targeted autonomic ganglia ablation on the incidence of atrial fibrillation, with data suggesting that there can be some benefit in this approach [70]. However, data is continuing to evolve about what exact role the ganglia play and which ones may play the most significant roles [71-73]. …”