The role of the posterior descending ganglionated plexus for neural control of cardiac electrophysiology

Ann-Kathrin Kahle (Düsseldorf)1, N. Klatt (Neustadt in Holstein)2, K. Scherschel (Düsseldorf)3, C. Jungen (Essen)4, P. Kuklik (Hamburg)5, F.-A. Alken (Düsseldorf)3, N. Klöcker (Düsseldorf)6, S. Willems (Hamburg)5, M. Kelm (Düsseldorf)1, E. Weber (Düsseldorf)7, U. Boeken (Düsseldorf)8, A. Lichtenberg (Düsseldorf)7, A. Bernhardt (Hamburg)9, S. Hakmi (Hamburg)5, D. Pauza (Kaunas)10, C. Meyer (Düsseldorf)3

1Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland; 2Schön Klinik Neustadt Klink für Innere Medizin und Kardiologie Neustadt in Holstein, Deutschland; 3Evangelisches Krankenhaus Düsseldorf Klinik für Kardiologie Düsseldorf, Deutschland; 4Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland; 5Asklepios Klinik St. Georg Kardiologie & internistische Intensivmedizin Hamburg, Deutschland; 6Heinrich-Heine-Universität Düsseldorf Düsseldorf, Deutschland; 7Universitätsklinikum Düsseldorf Klinik für Herzchirurgie Düsseldorf, Deutschland; 8Universitätsklinikum Düsseldorf Klinik für Kardiovaskuläre Chirurgie Düsseldorf, Deutschland; 9Universitäres Herz- und Gefäßzentrum Hamburg Klinik und Poliklinik für Herz- und Gefäßchirurgie Hamburg, Deutschland; 10Lithuanian University of Health Sciences Kaunas, Litauen


Background: The autonomic nervous system plays an integral role in cardiac physiology. Neuromodulation is increasingly developed as a therapeutical approach for cardiac arrhythmias, but translation into clinical practice is still necessary. While the atrially located ganglionated plexus have been studied in several species, there is limited knowledge regarding the functional characterization of ventricular ganglionated plexus.
Purpose: The aim of the present study was to assess the role of the posterior descending ganglionated plexus (PD-GP) for neural control of ventricular electrophysiology.
Methods and Results: First, a systematic literature review was performed revealing the presence of the PD-GP in dogs, swine and humans. To investigate whether the mouse may be useful as an animal model, a retrospective analysis of whole-mount immunohistological stained murine hearts was conducted (n=43) indicating the presence of ventricular ganglionated plexus in only 10% of hearts. Therefore, functional studies were performed in an ex-vivo retrograde-perfused porcine model (n=3) at baseline (pacing with a cycle length of 600 ms), during PD-GP high-frequency and local nicotine stimulation (Figure A+B). Wave propagation characteristics were determined by epicardial activation mapping demonstrating 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 (Figure C). Activation recovery intervals (ARIs) were analyzed with a multi-electrode sock placed around the epicardium displaying that high-frequency stimulation prolonged ARIs 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, while nicotine did not affect ARIs (right ventricle: 255.7±29.0 ms vs. left ventricle: 245.0±29.3 ms; P=0.677) (Figure D). Morphological analysis of explanted human hearts confirmed the presence of the PD-GP in close relationship to the posterior descending coronary artery within epicardial adipose tissue (Figure E+F).
Conclusions: Our findings suggest a species-dependent functional relevance of the PD-GP, with its modification in centrally denervated swine hearts resulting in global and regional changes in ventricular electrophysiological control. Clinical translation might be challenged by adjacent anatomical structures underlining the need for additional morphological and functional evaluation.

Figure: The role of the PD-GP for neural control of cardiac electrophysiology.
Visualization of the ex-vivo porcine model for PD-GP analysis with A, the study protocol, B, the ex-vivo set-up, C, representative color-coded isochronal MEA reconstructions and D, regional ARIs. E+F, Macrograph of the dorsal view of a human heart displaying the area of the PD-GP (marked), which disappears within the Sulcus interventricularis posterior. Determination of the PD-GP localization associated with the PDA is aggravated by distinct adjacent epicardial adipose tissue. 
ARI, activation recovery interval; CS, coronary sinus; HFS, high-frequency stimulation; LA, left atrium; LAA, left atrial appendage; LV, left ventricle; MEA, multi-electrode activation mapping; PDA, posterior descending coronary artery; PD-GP, posterior descending ganglionated plexus; RA, right atrium; RAA, right atrial appendage; RV, right ventricle.
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