During the past decade, catheter ablation of atrial fibrillation (AF) has evolved rapidly from an investigational procedure to its current status as a commonly performed ablation procedure in many major hospitals throughout the world. Surgical ablation of AF, using either standard or minimally invasive techniques, is also performed in many major hospitals throughout the world.

In 2007, an initial Consensus Statement on Catheter and Surgical AF Ablation was developed as a joint effort of the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society.1 The 2007 document was also developed in collaboration with the Society of Thoracic Surgeons and the American College of Cardiology. Since the publication of the 2007 document, there has been much learned about AF ablation, and the indications for these procedures have changed. Therefore the purpose of this 2012 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a Task Force, convened by the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society and charged with defining the indications, techniques, and outcomes of this procedure. Included within this document are recommendations pertinent to the design of clinical trials in the field of AF ablation, including definitions relevant to this topic.

This statement summarizes the opinion of the Task Force members based on an extensive literature review as well as their own experience. It is directed to all health care professionals who are involved in the care of patients with AF, particularly those who are undergoing, or are being considered for, catheter or surgical ablation procedures for AF. This statement is not intended to recommend or promote catheter ablation of AF. Rather the ultimate judgment regarding care of a particular patient …

2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design

The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT. Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart. The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via Gq proteins to phospholipase C-β. The high-affinity receptor state requires both Mg2+ and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has bee...

The Oxytocin Receptor System: Structure, Function, and Regulation

The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

https://repub.eur.nl/pub/104203/REPUB_104203-OA.pdf

2017 HRS / EHRA / ECAS / APHRS / SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation

2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design

Background

The extent and locations of intrinsic cardiac ganglia on the human heart were investigated to facilitate studying their function.



Methods

The locations and number of major intrinsic cardiac ganglia were determined in six human hearts by means of microdissection following methylene blue staining. Light and electron microscopic analyses were performed on right atrial and cranial medial ventricular ganglia obtained from 12 other human hearts.



Results

Gross anatomy: Collections of ganglia associated with nerves, i.e., ganglionated plexuses, were observed consistently in five atrial and five ventricular regions. Occasional ganglia were located in other atrial and ventricular regions. Atrial ganglionated plexuses were identified on 1) the superior surface of the right atrium, 2) the superior surface of the left atrium, 3) the posterior surface of the right atrium, 4) the posterior medial surface of the left atrium (the latter two fuse medially where they extend anteriorly into the interatrial septum), and 5) the inferior and lateral aspect of the posterior left atrium. Ventricular ganglionated plexuses were located in fat 1) surrounding the aortic root, 2) at the origins of the right and left coronary arteries (the latter extending to the origins of the left anterior descending and circumflex coronary arteries), 3) at the origin of the posterior descending coronary artery, 4) adjacent to the origin of the right acute marginal coronary artery, and 5) at the origin of the left obtuse marginal coronary artery. Microscopic anatomy: Ganglia ranged in size from those containing a few neurons to large ganglia measuring up to 0.5 × 1 mm. The human heart is estimated to contain more than 14,000 neurons. Neuronal somata varied in size and shape. Many axon terminals in intrinsic cardiac ganglia contained large numbers of small, clear, round vesicles that formed asymmetrical axodendritic synapses, whereas a few axons contained large, dense-cored vesicles.



Conclusions

The human intrinsic cardiac nervous system is distributed more extensively than was considered previously, most of its ganglia being located on the posterior surfaces of the atria and superior aspect of the ventricles. Each ganglion therein contains a variety of neurons that are associated with complex synaptology. Anat. Rec. 247:289-298, 1997. © 1997 Wiley-Liss, Inc.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291097-0185%28199702%29247%3A2%3C289%3A%3AAID-AR15%3E3.0.CO%3B2-L

Gross and microscopic anatomy of the human intrinsic cardiac nervous system

It is hypothesized that the heart possesses a nervous system intrinsic to it that represents the final relay station for the co-ordination of regional cardiac indices. This 'little brain' on the heart is comprised of spatially distributed sensory (afferent), interconnecting (local circuit) and motor (adrenergic and cholinergic efferent) neurones that communicate with others in intrathoracic extracardiac ganglia, all under the tonic influence of central neuronal command and circulating catecholamines. Neurones residing from the level of the heart to the insular cortex form temporally dependent reflexes that control overlapping, spatially determined cardiac indices. The emergent properties that most of its components display depend primarily on sensory transduction of the cardiovascular milieu. It is further hypothesized that the stochastic nature of such neuronal interactions represents a stabilizing feature that matches cardiac output to normal corporal blood flow demands. Thus, with regard to cardiac disease states, one must consider not only cardiac myocyte dysfunction but also the fact that components within this neuroaxis may interact abnormally to alter myocyte function. This review emphasizes the stochastic behaviour displayed by most peripheral cardiac neurones, which appears to be a consequence of their predominant cardiac chemosensory inputs, as well as their complex functional interconnectivity. Despite our limited understanding of the whole, current data indicate that the emergent properties displayed by most neurones comprising the cardiac neuroaxis will have to be taken into consideration when contemplating the targeting of its individual components if predictable, long-term therapeutic benefits are to accrue.

https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/expphysiol.2007.041178

Potential clinical relevance of the ‘little brain’ on the mammalian heart

Background: A three-dimensional description of the distribution and organization of the canine intrinsic cardiac nervous system was developed in order to characterize its full extent physiologically.

Methods: The anatomy of the canine intrinsic cardiac nervous system was investigated in 67 mongrel dogs by means of visulization following methylene blue staining as well as by light and electron microscopic analyses.

Results: Collections of ganglia associated with nerves, i.e., ganglionated plexuses, were identified in specific locations in epicardial fat and cardiac tissue. Distinct epicardial ganglionated plexuses were consistently observed in four atrial and three ventricular regions, with occasional neurons being located throughout atrial and ventricular tissues. One ganglionated plexus extended from the ventral to dorsal surfaces of the right atrium. Another ganglionated plexus, with three components, was identified in fat on the left atrial ventral surface. A ganglionated plexus was located on the mid-dorsal surface of the two atria, extending ventrally in the interatrial septum. A fourth atrial ganglionated plexus was located at the origin of the inferior vena cava extending to the dorsal caudal surface of the two atria. On the cranial surface of the ventricles a ganglionated plexus that surrounded the aortic root was identified. This plexus extended to the right and left main coronary arteries and origins of the ventral descending and circumflex coronary arteries. Two other ventricular ganglionated plexuses were identified adjacent to the origins of the right and left marginal coronary arteries. Intrinsic cardiac ganglia ranged in size from ones comprising one or a few neurons along the course of a nerve to ones as large as 1 × 3 mm estimated to contain a few hundred neurons. Intrinsic cardiac neuronal somata varied in size and shape, up to 36% containing multiple nucleoli. Electron microscopic examination demonstrated typical autonomic neurons and satellite cells in intrinsic cardiac ganglia. Many of their axon profiles contained large numbers of clear, round, and dense-core vesicles. Asymmetrical axodendritic synapses were common.

Conclusions: The canine intrinsic cardiac nervous system contains a variety of neurons interconnected via plexuses of nerves, the distribution of which is wider than previously assumed. © 1994 Wiley-Liss, Inc.

Gross and microscopic anatomy of the canine intrinsic cardiac nervous system.

The intrinsic cardiac nervous system has been classically considered to contain only parasympathetic efferent postganglionic neurones which receive inputs from medullary parasympathetic efferent preganglionic neurones In such a view, intrinsic cardiac ganglia act as simple relay stations of parasympathetic efferent neuronal input to the heart, the major autonomic control of the heart purported to reside solely in the brainstem and spinal cord Data collected over the past two decades indicate that processing occurs within the mammalian intrinsic cardiac nervous system which involves afferent neurones, local circuit neurones (interconnecting neurones) as well as both sympathetic and parasympathetic efferent postganglionic neurones As such, intrinsic cardiac ganglionic interactions represent the organ component of the hierarchy of intrathoracic nested feedback control loops which provide rapid and appropriate reflex coordination of efferent autonomic neuronal outflow to the heart In such a concept, the intrinsic cardiac nervous system acts as a distributive processor, integrating parasympathetic and sympathetic efferent centrifugal information to the heart in addition to centripetal information arising from cardiac sensory neurites A number of neurochemicals have been shown to influence the interneuronal interactions which occur within the intrathoracic cardiac nervous system For instance, pharmacological interventions that modify β-adrenergic or angiotensin II receptors affect cardiomyocyte function not only directly, but indirectly by influencing the capacity of intrathoracic neurones to regulate cardiomyocytes Thus, current pharmacological management of heart disease may influence cardiomyocyte function directly as well as indirectly secondary to modifying the cardiac nervous system This review presents a brief summary of developing concepts about the role of the cardiac nervous system in regulating the normal heart In addition, it provides some tentative ideas concerning the importance of this nervous system in cardiac disease states with a view to stimulating further interest in neural control of the heart so that appropriate neurocardiological strategies can be devised for the management of heart disease

/pdf/myocardial-ischaemia-and-the-cardiac-nervous-system-ukrr4gscj8.pdf

Myocardial ischaemia and the cardiac nervous system

Objective: Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with severe angina pectoris refractory to conventional therapeutic strategies. Clinical studies show that spinal cord stimulation (SCS) is a safe adjunct therapy for cardiac patients, producing anti-anginal as well as anti-ischemic effects. However, little information is yet available about the underlying mechanisms involved. Methods: In order to determine its mechanism of action, the effects of SCS on the final common integrator of cardiac function, the intrinsic cardiac nervous system, was studied during basal states as well as during transient (2 min) myocardial ischemia. Activity generated by intrinsic cardiac neurons was recorded in 9 anesthetized dogs in the absence and presence of myocardial ischemia before, during and after stimulating the dorsal T1–T2 segments of the spinal cord at 66 and 90% of motor threshold using epidural bipolar electrodes (50 Hz; 0.2 ms; parameters within the therapeutic range used in humans). Results: The SCS suppressed activity generated by intrinsic cardiac neurons. No concomitant change in monitored cardiovascular indices was detected. Neuronal activity increased during transient ventricular ischemia (46%), as well as during the early reperfusion period (68% compared to control). Despite that, activity was suppressed during both states by SCS. Conclusions: SCS modifies the capacity of intrinsic cardiac neurons to generate activity. SCS also acts to suppress the excitatory effects that local myocardial ischemia exerts on such neurons. Since no significant changes in monitored cardiovascular indices were observed during SCS, it is concluded that modulation of the intrinsic cardiac nervous system might contribute to the therapeutic effects of SCS in patients with angina pectoris.

/pdf/modulation-of-intrinsic-cardiac-neurons-by-spinal-cord-4bk1f93zbi.pdf

John A Armour

Papers

Gross and microscopic anatomy of the human intrinsic cardiac nervous system

Potential clinical relevance of the ‘little brain’ on the mammalian heart

Gross and microscopic anatomy of the canine intrinsic cardiac nervous system.

Myocardial ischaemia and the cardiac nervous system

Modulation of intrinsic cardiac neurons by spinal cord stimulation: implications for its therapeutic use in angina pectoris.