1, Overview of cardiac innervation It is currently believed that the nerve center regulating cardiovascular function is located in the medulla oblongata, which is called the cardiovascular center (cardiovascular center). The cardiovascular center realizes the neural regulation of the cardiovascular system through various cardiovascular reflexes. The nerves innervating the heart belong to the autonomic nervous system, the visceral nervous system, which includes the cardiac sympathetic and cardiac vagus nerves. In the study of the mechanism of atrial fibrillation, scholars apply the classification method of cardiac external (extrinsic) nerves and cardiac intrinsic (intrinsic) nerves to classify the innervation of the heart, which is more conducive to the scientific research and provides new clues for the neural mechanism of atrial fibrillation. The extrinsic nerves of the heart include the nuclei of the cardiovascular center, the sympathetic trunk, the vagal trunk, and the ganglia surrounding the heart; the intrinsic nerves of the heart consist of ganglia and nerve fibers within the epicardial fat pads, which form a network of nerves to regulate the activities of the heart. Yuan Zhang et al. applied vagal nerve trunk stimulation, representing external stimulation, and ganglionic stimulation, representing intrinsic stimulation, to the right upper pulmonary vein and the right auricle, and compared the atrial vulnerability measured at the two sites. It was found that vagal sensory stimulation had a more pronounced effect on the atrial window of vulnerability in the right auricle than did ganglionic stimulation (wider WOV), whereas it was ganglionic stimulation that produced a wider WOV at the right upper pulmonary vein.They then proposed the conclusion that the heart is innervated by both intrinsic and extrinsic nerves, and that the two types of nerves are differently distributed in different parts of the heart. Cardiac Vagus Nerve and the Mechanism of Atrial Fibrillation The concept that the cardiac autonomic nervous system plays an important role in the development and maintenance of atrial fibrillation has been generally accepted by scholars at home and abroad, and a large number of studies on the role of the autonomic nervous system, especially the cardiac vagus nerve, in the mechanism of fibrillation have been seen. Nevertheless, research on the role of the vagus nerve in the development of AF is still a hot spot in the etiology of AF. They mainly focus on the following aspects: the distribution of M receptors in the heart, the position of the Marshall’s ligament in the neural mechanism of AF episodes, and the different effects of vagal stimulation on the stimulation of the elderly and the under-aged. Acetylcholine and M Receptor Distribution and Atrial Fibrillation Mechanisms Numerous studies have shown that vagal stimulation has the effect of shortening the effective atrial refractory period, shortening the action potential time course, and increasing the dispersion of the action potential time course, as well as increasing the inducibility of atrial fibrillation. This notion has been accepted by the majority of scholars, and studies by Berenfeld O et al and Hirose M et al have found that rapid stimulation in the presence of acetylcholine can easily induce atrial fibrillation. Qing-Yan Zhao et al. carefully and systematically investigated the effects of vagal stimulation and M-receptor distribution density on the inducibility of AF. They compared the time course of action potentials in different parts of the atrium (including the left auricle, right auricle, left atrium, and right atrium) under different intensities of vagal stimulation, measured the distribution density of M receptors in different parts of the atrium by protein blotting, and measured the potassium channel-mediated potassium in-flow in different parts of the atrium by patch clamping. It was found that vagal stimulation could indeed shorten the action potential time course and increase the dispersion of the action potential time course. M receptor density as well as potassium ion inward flow were higher at the left and right auricles than at the left and right atria. They concluded that the left and right atria have an important role in vagally induced atrial fibrillation. Vagal Fibers in the Ligament of Marshall and the Mechanism of AF The ligament of Marshall is located above the left auricle, lateral to the left superior pulmonary vein, and converges into the coronary sinus (CS) through the left atrial oblique vein.The ligament of Marshall is the remnant of the left superior vena cava, which normally consists of folded pericardium containing blood vessels, muscle fibers, and nerve fibers.The ligament of Marshall is the main nerve fiber in the left auricle. The main nerve fibers in the ligament of Marshall are cholinergic nerve fibers and are in close contact with cardiac ganglia. At the same time, the ligament of Marshall also contains a certain number of adrenergic nerve fibers. XINGPENG LIU et al. studied the inducibility of atrial fibrillation and atrial electrophysiological indexes before and after ablation of the ligamentum maritimum and found that, after ablation of the ligamentum maritimum, the effective refractory period of the atrium connected to the ligamentum maritimum was significantly prolonged (reduced vulnerability) and the inducibility of atrial fibrillation was significantly reduced. By comparing atrial fragmentation potentials in the ligamentum maritimus region with those in the pulmonary veins during episodes of atrial fibrillation, they found that fragmentation potentials in the ligamentum maritimus region were more frequent than those in the pulmonary veins, and they proposed the idea that the ligamentum maritimus plays an important role in the maintenance of atrial fibrillation. Age affects the vagal influence on the atrium Advanced age, a risk factor for atrial fibrillation has been recognized by national and international scholars. However, a large number of studies have shown that there is a difference in the mechanism of AF between people of advanced age and people of younger age, and this difference in mechanism is currently unknown. The search for differences in the mechanisms of atrial fibrillation at different ages in terms of the innervation of the heart is an important clue in current scientific research. Yu Hui Yang et al, using 36-48 month old rabbits (senescent group) to represent advanced age, studied the distribution of M-like receptors in the heart at different ages and the effect of parasympathetic nerves on the susceptibility to atrial fibrillation, and they found that the distribution of M-like receptors varied in different locations of the heart, and was highest in the free wall of the left atrium. There was a significant increase in M receptor expression in the senescent group compared with the mature group, and the inducibility of atrial fibrillation was higher in the senescent group than in the other groups. From this, they concluded that the altered distribution of M-like receptors, which is closely related to age, may be responsible for the high prevalence of AF in the aging group. MÁRIO MARTINS OLIVEIRA et al, performed and compared the results of the upright tilt test in patients with paroxysmal atrial fibrillation of advanced age and patients with vasovagal syncope of the same age. They found that elderly patients with paroxysmal atrial fibrillation and elderly patients with vasovagal syncope can have positive passive upright tilt test, and even in the process of the experiment, they can see the triggering of paroxysmal atrial fibrillation, and they called the passive tilt test of elderly atrial fibrillation as “false-positive”. This shows that the occurrence of atrial fibrillation in the elderly is closely related to vagal hyperactivity, and using the imbalance of the autonomic nervous system as an entry point to look for the differences in the mechanisms of the occurrence of atrial fibrillation in the elderly and the elderly can be the direction of scientific research in the future. 3. Cardiac sympathetic nerves and the mechanism of atrial fibrillation As mentioned earlier, the cardiac vagus nerve can change electrophysiologic indexes represented by the effective atrial refractory period, which in turn increases the inducibility of atrial fibrillation. In contrast to the cardiac vagus nerve, the cardiac sympathetic nerve can also increase the inducibility of AF, which is induced by triggered activity in the presence of increased sympathetic activity. However, the effect of the cardiac sympathetic nerve on electrophysiologic indices of the atria is controversial in national and international studies. Compared with the studies on the effect of cardiac vagus nerve on the occurrence of atrial fibrillation, domestic and international studies on cardiac sympathetic nerves and the mechanism of atrial fibrillation occurrence are a little thin. Rahul N. Doshi et al. investigated the relationship between chronic atrial fibrillation induced by prolonged rapid atrial stimulation and sympathetic nerves using isoproterenol as a sympathetic nerve stimulus. It was found that atrial fibrillation could be induced by the intervention of isoproterenol with prolonged rapid atrial stimulation, but not in the absence of rapid stimulation, and that isoproterenol induced autonomic electrical activity originating from the ligamentum maritimus, which disappeared after ablation of the ligamentum maritimus. Cellular immunology showed that the ligament of Marshall contains complex hydroxylase (+) nerve fibers, i.e., adrenergic nerve fibers. They concluded that adrenaline induces atrial fibrillation through the evocation of ectopic agonism, and that the sympathetically innervated Marshall’s ligament is important in this process. J. Vijay Jayachandran et al. applied PET imaging (hydroxyephedrine as contrast agent) to study the electrophysiologic remodeling of the atria under prolonged rapid atrial stimulation. It was found that prolonged rapid atrial stimulation resulted in an increase in the density of adrenergic nerve fiber distribution in the atria. The concentration of norepinephrine in isolated atrial tissue increased. And the circumference of atrial cells (cycle length) was longer in the right atrium than in the left atrium, and the density of adrenergic nerve fiber divisions was higher in the right atrium than in the left atrium. They concluded that rapid atrial stimulation can produce cardiac sympathetic remodeling, i.e., increased density of sympathetic nerve distribution, and that sympathetic nerve fibers have an effect on atrial electrophysiological indexes (different from domestic and international studies). Some scholars categorize atrial fibrillation into “vagal atrial fibrillation” and “sympathetic atrial fibrillation” according to the different vagal and sympathetic sensitivities of atrial fibrillation. The former occurs mainly at night, during sleep and eating, and is sensitive to vagal stimulation; the latter occurs mainly during the day, during exercise, and is sensitive to sympathetic stimulation. The classification of atrial fibrillation into “vagal atrial fibrillation” and “sympathetic atrial fibrillation” can better guide the study of the neural mechanism of atrial fibrillation. The effect of ventral denervation on the incidence of atrial fibrillation after coronary artery bypass grafting The incidence of postoperative atrial fibrillation after coronary artery bypass grafting ranges from 19% to 27%, and it is the main cause of postoperative death. Postoperative atrial fibrillation occurs mainly on the second and third postoperative days. A large number of reports on cardiac denervation for the prevention of atrial fibrillation after coronary artery bypass grafting can be seen in the literature and are somewhat controversial. Melo J et al, conducted a clinical randomized controlled study of ventral cardiac denervation prior to coronary artery bypass grafting for the prevention of postoperative atrial fibrillation after bypass grafting. The number of cases reached 207 in the case group and 219 in the control group, and it was found that ventral denervation of the heart prior to coronary artery bypass grafting took only 5±2 minutes longer than in the control group and had no significant complications. Ventral denervation resulted in a significant reduction in atrial fibrillation after bypass surgery and in the duration of atrial fibrillation episodes compared with the control group. The preventive effect of ventral denervation of the heart on atrial fibrillation was higher in the younger age group than in the older age group. They concluded that ventral denervation of the heart is a safe and effective measure to prevent the development of atrial fibrillation after bypass surgery. A different conclusion was reached in a study by Omran AS et al. They enrolled 220 patients undergoing coronary artery bypass grafting and categorized them into cases and controls according to whether or not they underwent ventral denervation of the atria and found that instead of reducing the incidence of postoperative atrial fibrillation, ventral denervation of the heart tended to increase postoperative atrial fibrillation compared to controls. Multiple regression analysis showed that age and ventral denervation of the heart were risk factors for postoperative atrial fibrillation after bypass surgery. They concluded that ventral denervation of the heart during bypass surgery should not be performed as a preventive measure against postoperative atrial fibrillation and that ventral denervation of the heart is a risk factor for postoperative atrial fibrillation. CONCLUSION: The heart is subject to dual autonomic innervation by the cardiac vagus and cardiac sympathetic nerves, and the cardiac vagus and cardiac sympathetic nerves have different roles in the onset and development of atrial fibrillation. The cardiac vagus nerve can increase atrial vulnerability to AF through its influence on atrial electrophysiologic indexes, thus promoting the development of AF; the cardiac sympathetic nerve also promotes the development of AF, but its influence on atrial electrophysiology is smaller. The role of cardiac sympathetic nerves in the mechanism of AF has been less well studied at home and abroad. The search for the cause of atrial fibrillation in the innervation of the heart and the autonomic nervous system of the heart has been a hot spot in the etiology of atrial fibrillation in recent years.