Key result
Mapping the right atrial ganglionated plexus shows intrinsic cardiac neurons directly influence the pacemaking site.
Why the study?
Neuroablative techniques to modulate cardiac function yield variable and sometimes deleterious results, reflecting major gaps in the understanding of cardiac neural control.
Provides a comprehensive neuroanatomic atlas of the RAGP-SAN complex, demonstrating for the first time that intrinsic cardiac neurons influence the pacemaking site in the heart.
Extends neuroanatomic mapping of intrinsic neurons; hypothesis-generating for sinus node neuromodulation in humans.
Cardiac function is under exquisite intrinsic cardiac neural control. Neuroablative techniques to modulate control of cardiac function are currently being studied in patients, albeit with variable and sometimes deleterious results. Recognizing the major gaps in our understanding of cardiac neural control, we sought to evaluate neural regulation of impulse initiation in the sinoatrial node as an initial discovery step. Here, we report an in-depth, multi-scale structural and functional characterization of the innervation of the sinoatrial node (SAN) by the right atrial ganglionated plexus (RAGP) in porcine and human hearts. Combining intersectional strategies including tissue clearing, immunohistochemical and ultrastructural techniques, we have delineated a comprehensive neuroanatomic atlas of the RAGP-SAN complex. The RAGP shows significant phenotypic diversity of neurons while maintaining predominant cholinergic innervation. Cellular and tissue-level electrophysiologic mapping and ablation studies demonstrate interconnected ganglia with synaptic convergence within the RAGP to modulate SAN automaticity, atrioventricular (AV) conduction and left ventricular (LV) contractility. For the first time, we demonstrate that intrinsic cardiac neurons influence the pacemaking site in the heart. This provides an experimental demonstration of a discrete neuronal population controlling a specific geographic region of the heart (SAN) that can serve as a framework for further exploration of other parts of the intrinsic cardiac nervous system (ICNS) in mammalian hearts and for developing targeted therapies.
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Hanna et al. (2020) studied Sinoatrial node innervation. Structural and functional mapping of the right atrial ganglionated plexus in porcine and human hearts demonstrated that intrinsic cardiac neurons directly influence the pacemaking site in the heart.
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