Translational approach to ventricular innervation: the posterior descending ganglionated plexus.

Abstract

Aims: Modulation of cardiac neural control is increasingly explored to treat cardiac arrhythmias. While the atrially located ganglionated plexus (GPs) have been studied intensively, characterization of ventricular GPs is sparse. This proof-of-principle study aimed to assess the role of the posterior descending GP (PDGP) for neural control of cardiac electrophysiology, while offering a translational roadmap into clinical practice.

Methods and results: Since an initial systematic literature review revealed the PDGP as a small, consolidated GP on the posterior left ventricle in dogs, swine and humans, we subsequently conducted morphological C57BL/6 murine studies (n=43) indicating ventricular GPs in only 10% of hearts. Based on our initial findings, in a proof-of-principle study analyzing 4,300 local unipolar electrograms from a multi-electrode sock, the impact of functional PDGP modulation was studied in an ex-vivo retrograde-perfused porcine model. Wave propagation characteristics determined by epicardial activation mapping demonstrated increased dispersion of conduction velocity during high-frequency (8.52±2.24 radian vs. 2.79±0.89 radian; P=0.018) and nicotine stimulation (19.79±6.49 radian vs. 2.79±0.89 radian; P=0.044) compared to paced rhythm. High-frequency stimulation prolonged activation recovery intervals in the posterior (257.8±6.7 ms vs. 244.8±1.9 ms; P=0.044) and basal (258.1±4.2 ms vs. 244.8±1.9 ms; P=0.039) right ventricle compared to the posterior left ventricle. Analysis of explanted human hearts confirmed the presence of the PDGP within epicardial adipose tissue near its eponymous coronary artery and the posteromedial left atrial GP. Three-dimensionally reconstructed human hearts suggested the PDGP localization characterized by interpatient anatomical variability.

Conclusion: The present translational approach to ventricular innervation demonstrates first evidence of the functional relevance of the PDGP, with morphological findings indicating species-related differences. Novel imaging modalities might pave the way for future functional and therapeutic interventions.