Autonomic mechanism for initiation of rapid firing from atria and pulmonary veins: evidence by ablation of ganglionated plexi

Lu, Zhibing; Scherlag, Benjamin J.; Lin, Junshan; Yu, Lilei; Guo, Jihong; Niu, Guodong; Jackman, Warren M.; Lazzara, Ralph; Jiang, Hong; Po, Sunny S.

doi:10.1093/cvr/cvp194

Cited by 116 publications

(91 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…81,84,85 Animal studies have demonstrated that stimulation of GP located around the pulmonary veins can reduce the number of atrial extrastimuli required to initiate AF, and that neuronal/autonomic blockade with drugs or GP ablation can prevent AF induction. 86,87 Because GP are located near the pulmonary veins, conventional PVI can often coincidently eliminate these areas, and it has been suggested that ablation of GP may help explain the success of PVI. In an early study, Pappone and colleagues assessed for vagal responses (bradycardia, hypotension, heart block or asystole) which occurred within a few seconds after the onset of ablation.…”

Section: The Influence Of the Autonomic Nervous System And Ganglionatmentioning

confidence: 99%

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

Waks

Josephson²

2014

Arrhythmia &Amp; Electrophysiology Review

View full text Add to dashboard Cite

Atrial fibrillation (AF), the most common sustained arrhythmia, is a leading cause of stroke, and is associated with significant morbidity and mortality worldwide. Despite its frequency, clinical importance, and advances in technology and our knowledge of the molecular, ionic and physiological fundamentals of cardiac electrophysiology, our limited understanding of the mechanisms that initiate and sustain AF has prevented us from being able to truly cure this arrhythmia with antiarrhythmic drugs and/or ablation. This contrasts with other arrhythmias, such as AV nodal tachycardia or circus movement tachycardia using an accessory pathway, which have well-defined mechanisms and circuits that can be safely targeted with high rates of cure. The observations that AF may have different mechanisms in different patients, and that paroxysmal, persistent and permanent forms of AF may differ in how they are initiated and sustained, only serves to reinforce our lack of understanding of this ubiquitous arrhythmia. Historical Mechanisms of Atrial Fibrillation and the Multiple Wavelet HypothesisInterest and understanding of the mechanism of AF began to take form in the early 1900s. Given the chaotic and irregular nature of AF on the surface electrocardiogram, rapid firing of automatic atrial foci was considered a potential mechanism. However, after the seminal work of Mayer 1 , Mines 2 and Garrey 3 in laying the foundation for describing and understanding reentrant arrhythmias, atrial reentrant circuits emerged as the likely drivers of AF.4-7 Although these theories were conceptually sound, it was impossible to prove a specific mechanism with the technology of the time. Moe et al. demonstrated that it was probabilistically unlikely that a large number of simultaneous wavefronts would all die out simultaneously, and AF would therefore perpetuate. However, if the number of simultaneous wavelets were small and/or below a critical value (between 15 and 30 in Moe's computer model), 9 at some point all reentrant wavefronts would be simultaneously extinguished, and AF would therefore terminate. 8,9 Allessie et al. provided experimental evidence supporting this mechanism in a canine heart model of AF where four to six simultaneous reentrant wavelets were needed to sustain arrhythmia. 10 Further evidence supporting multiple wavelets in AF was demonstrated in a separate model, which evaluated the effect of various antiarrhythmic drugs on canine myocardium. This model demonstrated that termination of AF was associated with a reduction AbstractAtrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, yet our understanding of the mechanisms that initiate and sustain this arrhythmia remains quite poor. Over the last 50 years, various mechanisms of AF have been proposed, yet none has been consistently observed in both experimental studies and in humans. Recently, there has been increasing interest in understanding how spiral waves or rotors -which are specific, organised forms of functional reentry -su...

show abstract

Section: The Influence Of the Autonomic Nervous System And Ganglionatmentioning

confidence: 99%

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

Waks

Josephson²

2014

Arrhythmia &Amp; Electrophysiology Review

View full text Add to dashboard Cite

show abstract

“…A comparatively dense network of nerve endings is found particularly at the insertion the pulmonary veins in the left atrium, where it is associated with the development of atrial fibrillation [10]. In addition to the electrical isolation of the pulmonary vein opening from the atrial myocardium, initial clinical data indicate that the targeted ablation of autonomic ganglia could also exert an antiarrhythmic effect [11]. However, the identification of suitable epicardial ganglions and their selective ablation is technically sophisticated and currently has only limited clinical application.…”

Section: Intrinsic Systemmentioning

confidence: 99%

Cardiac Arrhythmia following Stroke

Kallmünzer

Schwab

2017

Neurology International Open

View full text Add to dashboard Cite

The autonomous innervation of the heart is based on a complex interaction of central and peripheral mechanisms in sympathetic and parasympathetic parts of the autonomic nervous system (▶Fig. 1). An extrinsic cardiac innervation is distinguished from an intrinsic one. Extrinsic systemTo put it simply, a center of the efferent parasympathetic innervation of the heart is found in the nucleus of the medulla oblongata, especially in the nucleus dorsalis [1]. The preganglionic fibers leave the central nervous system along with the vagus nerve and are connected to the second neuron in cardiac ganglion cells. Sympath etic fibers, on the other hand, originate from the nucleus intermediolateralis of the upper thoracic cord [2]. They reach the plexus cardiacus by means of the so-called "cardiac nerves" (usually 4 right-sided and 3 left-sided nervi cardiaci), after interposition in the border ganglia, especially in the ganglion stellatum. For the control of cardiac functions, the profound part of the plexus cardiacus is decisive; it extends between the tracheal bifurcation and the aortic arch, divides into a right and left half and in its further course follows the right or left coronary artery. The function of the efferent limb is modified by afferents from various organ systems, including the gastrointestinal tract or the carotissinus, by means of multisynaptic reflex arcs (e. g., baroreflex) [1]. In addition, in the blood circulating catecholamine, the release of which in the adrenal system is also subject to the autonomic system, mediates beta-adrenergic effects on the myocardium. It is postulated that dysbalances in the extrinsic system, in particular the pathological disinhibition of sympathetic activity, are relevant to the development of cardiac arrhythmias [1,[3][4][5]. For example, extensive brain stem damage can lead to suppression of central parasympathetic functions and overcoming of sympathetic tone [6], thus promoting the occurrence of cardiac arrhythmias. Conversely, blockade of the ganglion stellatum or renal sympathetic denervation should reduce the risk of ventricular arrhythmias in patients with prolonged-QT syndromes [7]. It is noteworthy in this context that extensive cardiac denervation, which may be present after orthotopic heart transplantation, is associated with a lower risk of supra ventricular rhythm disturbances, especially atrial fibrillation [8]. In these cases, the denervation should have protective effects and protect the myocardium from the autonomic imbalances of the extrinsic system before transmission. It should be noted, however, that organ donors are usually much younger and the vascular damage to the donor organs is often less pronounced, which significantly reduces the risk of atrial fibrillation independent of cardiac denervation [9].

show abstract

“…Multiple tiers of neuronal processing occur within the cardiac neuronal hierarchy that ultimately acts to coordinate neuronal inputs to the heart (4, 7, 13). Stresses, either pathological or physiological, may disrupt the balance of efferent neuronal inputs that can lead to altered cardiac function (6,22). As such, novel therapies that overcome any such imbalance in cardiac control, as represented by neuromodulation of the ICN via SCS, may moderate excessive activation of the ICN in response to transduction of pathological cardiac stressors.…”

Section: Perspectives and Significancementioning

confidence: 99%

“…EXCESSIVE ACTIVATION OF SELECT inputs to the intrinsic cardiac nervous system (ICN) are known to elicit atrial arrhythmias in normal (9,22,28) and pathophysiological states (11,30). Discrete activation of the axons in select mediastinal nerves can reproducibly elicit self-terminating periods of atrial tachyarrhythmias/fibrillation (ATF) (9).…”

mentioning

confidence: 99%

Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias

Gibbons

Southerland

Hoover

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ϳ4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential.

show abstract

Autonomic mechanism for initiation of rapid firing from atria and pulmonary veins: evidence by ablation of ganglionated plexi

Cited by 116 publications

References 22 publications

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

Cardiac Arrhythmia following Stroke

Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias

Contact Info

Product

Resources

About