Kahle Ann-Kathrin, Klatt Niklas, Scherschel Katharina, Jungen Christiane, Kuklik Pawel, Alken Fares-Alexander, Klöcker Nikolaj, Willems Stephan, Weber Elvira, Boeken Udo, Lichtenberg Artur, Bernhardt Alexander, Hakmi Samer, Pauza Dainius H, Meyer Christian
Division of Cardiology, Angiology, Intensive Care Medicine, EVK Düsseldorf, cNEP, cardiac Neuro- and Electrophysiology Research Consortium, Kirchfeldstrasse 40, 40217 Düsseldorf, Germany.
Department of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Europace. 2025 May 7;27(5). doi: 10.1093/europace/euaf099.
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.
Since an initial systematic literature review revealed the PDGP as a small, consolidated GP on the posterior left ventricle (LV) 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 analysing 4300 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 LV. 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 inter-patient anatomical variability.
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.
对心脏神经控制进行调节以治疗心律失常的研究日益深入。虽然位于心房的神经节丛（GPs）已得到深入研究，但对心室GPs的特征描述却很稀少。这项原理验证研究旨在评估后降支神经节丛（PDGP）在心脏电生理神经控制中的作用，同时提供一条转化为临床实践的路线图。
最初的系统文献综述显示，PDGP是犬、猪和人类左心室后壁上一个小的、集中的神经节丛。随后，我们对C57BL/6小鼠进行了形态学研究（n = 43），结果表明只有10%的心脏存在心室GPs。基于我们最初的发现，在一项原理验证研究中，我们分析了来自多电极套的4300个局部单极电图，在离体逆行灌注猪模型中研究了功能性PDGP调节的影响。通过心外膜激活标测确定的波传播特征表明，与起搏节律相比，在高频（8.52±2.24弧度对2.79±0.89弧度；P = 0.018）和尼古丁刺激（19.79±6.49弧度对2.79±0.89弧度；P = 0.044）期间，传导速度的离散度增加。与左心室后壁相比，高频刺激延长了右心室后壁（257.8±6.7 ms对244.8±1.9 ms；P = 0.044）和基底部（258.1±4.2 ms对244.8±1.9 ms；P = 0.039）的激活恢复间期。对离体人心脏的分析证实，在其同名冠状动脉和左心房后内侧神经节丛附近的心外膜脂肪组织中存在PDGP。三维重建的人心脏表明，PDGP的定位存在个体间解剖变异。
目前对心室神经支配的转化研究方法首次证明了PDGP的功能相关性，形态学研究结果表明存在物种差异。新的成像方式可能为未来的功能和治疗干预铺平道路。
