Introduction

Following demonstration that the intrinsic cardiac nervous system (ICNS) is a potential modulator of the initiation and perpetuation of atrial fibrillation and the major reason for several bradyarrhythmias, catheter-based autonomic modulation emerged as a novel therapy in recent years (1,2). The anatomy and physiology of the ICNS are relevant to the cardiac electrophysiologist because this invisible anatomic structure is becoming an important target during radiofrequency catheter ablation.

Principles of Autonomic Innervation of the Heart

Autonomic innervation of the heart may be divided into the extrinsic (central) cardiac nervous system and the ICNS. By definition, a ganglion is a cluster of neuron cell bodies in the peripheral nervous system. The extrinsic part consists of the nuclei in the brain stem and along the thoracic segments of the spinal cord, as well as their axons en route to the heart. Pre-ganglionic sympathetic axons arise from the spinal cord, synapse with the second sympathetic neurons in the sympathetic chain or intrinsic cardiac ganglia, and proceed as the post-ganglionic sympathetic axons innervating the cardiomyocytes. Pre-ganglionic parasympathetic axons of the vagus nerve primarily arise from the dorsal vagus nerve and possibly the nucleus ambiguus and synapse with the second parasympathetic neurons within epicardial ganglionated nerve plexuses.

Microanatomy of the Intrinsic Cardiac Nervous System

Most neurons of the ICNS reside inside epicardial ganglia that are interconnected by intrinsic nerves on the human atria and ventricles (Figure 1) (3). Earlier reports suggested that only the second parasympathetic neurons exist in the ganglia. However, according to more recently published reports, these ganglia contain both efferent parasympathetic and sympathetic neuronal somata and presumably local circuit neurons or interneurons, and these are very densely packed, overlapping, and of widely varying sizes