Innervation of the Human Atrioventricular Node via the Inferior Pyramidal Space: Characterization Using Intersectional Strategies

BACKGROUND: The inferior pyramidal space (IPS), the epicardial adipose tissue extending from the inferior crux of the heart, contains the atrioventricular node (AVN) at its apex. However, innervation of the human AVN via the IPS remains unknown. METHODS: Seven whole-mount samples of the human IPS involving the AVN were obtained from hearts rejected for transplantation (85.7% male, 49.4±12.8 years old). The IPS was further divided into the anterior (behind the floor of the triangle of Koch) and posterior (within the Eustachian ridge) fat pads relative to the coronary sinus. A whole-mount tissue-clearing method with immunohistochemical staining was applied to each fat pad to count and characterize the nerve fascicles ≥10 µm and ganglia ≥6000 µm 2 . RESULTS: Within the anterior fat pad, sympathetic nerve fascicles ascended towards the AVN along the AVN artery, whereas nonsympathetic nerve fascicles approached the AVN from the superior and posterior aspects without a consistent relationship to the AVN artery. Within the IPS, sympathetic nerve fascicles were thicker than nonsympathetic nerve fascicles (51.7±32.8 versus 22.1±10.6 µm; P <0.001). The ganglia, which were mainly nonsympathetic, were found predominantly within the posterior fat pad compared with the anterior fat pad (63.2±40.3 versus 5.8±5.0; P <0.01). The compact AVN regions were devoid of thick nerve fascicles and ganglionated plexuses but filled with a fine meshwork of both sympathetic and nonsympathetic nerve fibers. CONCLUSIONS: The human IPS exhibits a distinct pattern of autonomic innervation and distribution of ganglia. These neural structures are likely to contribute to the physiological control of the human AVN and could be a novel target for neuromodulation to restore normal AVN function.