Neural substrate for atrial fibrillation: implications for targeted parasympathetic blockade in the posterior left atrium

2008 ◽  
Vol 294 (1) ◽  
pp. H134-H144 ◽  
Author(s):  
Rishi Arora ◽  
Joseph S. Ulphani ◽  
Roger Villuendas ◽  
Jason Ng ◽  
Laura Harvey ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Refractory Period ◽  
Left Atrial Appendage ◽  
Pulmonary Veins ◽  
Nerve Fibers ◽  
Effective Refractory Period ◽  
Nerve Bundles ◽  
Neural Substrate ◽  
Fibrofatty Tissue

The parasympathetic (P) nervous system is thought to contribute significantly to focal atrial fibrillation (AF). Thus we hypothesized that P nerve fibers [and related muscarinic (M2) receptors] are preferentially located in the posterior left atrium (PLA) and that selective cholinergic blockade in the PLA can be successfully performed to alter vagal AF substrate. The PLA, pulmonary veins (PVs), and left atrial appendage (LAA) from six dogs were immunostained for sympathetic (S) nerves, P nerves, and M2 receptors. Epicardial electrophysiological mapping was performed in seven additional dogs. The PLA was the most richly innervated, with nerve bundles containing P and S fibers (0.9 ± 1, 3.2 ± 2.5, and 0.17 ± 0.3/cm2 in the PV, PLA, and LAA, respectively, P < 0.001); nerve bundles were located in fibrofatty tissue as well as in surrounding myocardium. P fibers predominated over S fibers within bundles (P-to-S ratio = 4.4, 7.2, and 5.8 in PV, PLA, and LAA, respectively). M2 distribution was also most pronounced in the PLA (17.8 ± 8.3, 14.3 ± 7.3, and 14.5 ± 8 M2-stained cells/cm2 in the PLA, PV, and LAA, respectively, P = 0.012). Left cervical vagal stimulation (VS) caused significant effective refractory period shortening in all regions, with easily inducible AF. Topical application of 1% tropicamide to the PLA significantly attenuated VS-induced effective refractory period shortening in the PLA, PV, and LAA and decreased AF inducibility by 92% ( P < 0.001). We conclude that 1) P fibers and M2 receptors are preferentially located in the PLA, suggesting an important role for this region in creation of vagal AF substrate and 2) targeted P blockade in the PLA is feasible and results in attenuation of vagal responses in the entire left atrium and, consequently, a change in AF substrate.

Hemodynamic Changes in the Left Atrium due to Atrial Fibrillation

2011 ◽  
Author(s):  
Kenichi Funamoto ◽  
Ryo Koizumi ◽  
Toshiyuki Hayase ◽  
Muneichi Shibata ◽  
Tomoyuki Yambe
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
High Frequency ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Pulmonary Veins ◽  
Hemodynamic Changes ◽  
Structure Interaction ◽  
Interaction Simulation

The left atrium (LA), which connects four pulmonary veins (PVs) to the left ventricle (LV), has a characteristic shape called the left atrial appendage (LAA) under the left PV. Atrial fibrillation (AF) is a heart disease, by which irregular electrical signals with high-frequency contraction (> 400 bpm) occur in the LA. Although AF itself is not fatal, it may cause thrombus formation, resulting to cerebral infarction. In this study, hemodynamics in the LA with/without AF was investigated by means of fluid-structure interaction simulation.

The ligament of Marshall as a parasympathetic conduit

2007 ◽  
Vol 293 (3) ◽  
pp. H1629-H1635 ◽  
Author(s):  
Joseph S. Ulphani ◽  
Rishi Arora ◽  
Jack H. Cain ◽  
Roger Villuendas ◽  
Sharon Shen ◽  
...  
Keyword(s):  
Left Atrium ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Pulmonary Veins ◽  
Stellate Ganglion ◽  
Nerve Fibers ◽  
Atrial Appendage ◽  
Cholinergic Nerves ◽  
Left Vagus

The objective of the study was to investigate the morphology, distribution, and electrophysiological profile of the autonomic fibers that innervate the ligament of Marshall (LOM). Gross anatomical dissections were performed in 10 dogs. Sections of the left vagus nerve, left stellate ganglion, and the LOM were immunostained to identify adrenergic and cholinergic nerves. Hearts were also stained for acetylcholinesterase to identify epicardial cholinergic nerves. In vivo electropyhsiological studies were performed in another 10 dogs before and after LOM ablation. The anatomical examination revealed that the LOM is innervated by a branch of the left vagus. Immunohistochemistry confirmed that these nerve bundles are predominantly cholinergic (cholinergic-to-adrenergic ratio of 12.6 ± 3.9:1). Cholinergic nerves originating in the LOM were found to innervate surrounding left atrial structures, including the pulmonary veins, left atrial appendage, coronary sinus, and posterior left atrial fat pad. Ablation of the LOM significantly attenuated effective refractory period shortening at distant sites, such as pulmonary veins and left atrial appendage, in response to vagal stimulation (vagal-induced ERP decrease in the left atrium: baseline vs. postablation = 17 vs. 4%; P = 0.0056). In conclusion, the LOM contains a predominance of cholinergic nerve fibers. Cholinergic fibers arising from the LOM innervate surrounding structures and contribute to the electrophysiological profile of the left atrium. These findings may provide a basis for the role of the LOM in the genesis and maintenance of atrial fibrillation.

scholarly journals Electrical anatomy of the left atrium during atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
P Adragao ◽  
D Nascimento Matos ◽  
F Costa ◽  
P Galvao Santos ◽  
G Rodrigues ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Left Atrium ◽  
Pulmonary Vein ◽  
Refractory Period ◽  
Cycle Length ◽  
Low Voltage ◽  
Pulmonary Veins ◽  
Short Cycle ◽  
Superior Pulmonary Vein

Abstract Introduction Twenty years ago, pulmonary veins (PV) ostia were identified as the left atrium (LA) areas with the shortest refractory period during sinus rhythm. Pulmonary veins isolation (PVI) became standard of care, but clinical results are still suboptimal. Today, a special tool using the Carto® electroanatomical mapping (EAM) allows for AF cycle length mapping (CLM), to identify the areas in the left atria with shortest refractory period, during atrial fibrillation. Using this EAM tool, our study aimed to find the LA areas with the shortest refractory period to better recognize electrical targets for catheter ablation. Methods Retrospective analysis of an unicentric registry of individuals with symptomatic drug-refractory AF who underwent PVI with Carto® EAM. CLM was performed with a high-density mapping Pentaray® catheter before and after PVI and in 4 redo procedures. We assessed areas of short cycle length (SCL) (defined as 120 to 250ms), and their relationships with complex fractionated atrial electrograms (CFAE), and low-voltage zones (from 0.1 to 0.3mV). Results A total of 18 patients (8 men, median age 63 IQR 58–71 years) were included. Most patients presented with persistent AF (n=12, 67%), and 4 patients (22%) had a previous PVI. The mean shortest measured cycle length in AF was 140ms (SD ±27ms). All patients presented areas of SCL located in the PVs or their insertion, 70% in the posterior/roof region adjacent to the left superior pulmonary vein (LSPV) (figure 1) and 60% in the anterior region of the right superior pulmonary vein (RSPV). These two areas remained the fastest even after PVI. The anterior mitral region rarely presented SCL (17%). SCL were related to low-voltage areas in 94% and were adjacent to CFAE. Low-voltage areas and CFAE were more frequent and had a larger LA dispersion than SCL. Conclusion We confirmed in 3D mapping that PVs are the LA zones with shortest refractory period, not only in sinus rhythm but also during AF. The persistence of SCL areas in the border zones of the PVI lines suggest the benefit of a more extensive CLM guided ablation. Larger studies are needed. FUNDunding Acknowledgement Type of funding sources: None. Short cycle length mapping

scholarly journals Short- and mid-term results of thoracoscopic atrial fibrillation ablation

2020 ◽  
Vol 8 (4S) ◽  
pp. 82-88
Author(s):  
E. A. Khomenko ◽  
S. E. Mamchur ◽  
K. A. Kozyrin ◽  
R. S. Tarasov ◽  
K. V. Bakovsky
Keyword(s):  
Atrial Fibrillation ◽  
Radiofrequency Ablation ◽  
Catheter Ablation ◽  
Sinus Rhythm ◽  
Left Atrium ◽  
Atrial Flutter ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Pulmonary Veins ◽  
One Year

Aim. Evaluation of short- and mid-term (up to one year) results of aт atrial fibrillation thoracoscopic radiofrequency ablation (TRFA) combined with left atrial appendage resection.Methods. 10 patients with persistent AF were included in the study. In 5 cases surgical ablation was performed as the primary intervention and in 5 cases surgery were preceded by two unsuccessful catheter procedures. Age of the patients was 54.4 (41; 63) years, duration of arrhythmic anamnesis – 5.6 (4.8; 6.8) years, anteroposterior size of the left atrium – 4.7 (45; 51 mm), LV ejection fraction – 63 (58; 68) %. TRFA included an isolation of right and left pulmonary veins, ablation lines along the roof and base of posterior wall of the left atrium, left atrial appendage resection.Results. In all cases of TRFA exit-block from the pulmonary veins was achieved. Among 10 procedures, a stable sinus rhythm was documented in 6 patients. In the remaining 4 patients AF was observed only in one case, and the other three demonstrated atypical atrial flutter, that given us a reason to repeat catheter procedures. In three cases of left atrial flutter, catheter ablation led to sinus rhythm restoration, and in case of AF and total sclerosis of left atrium a decision to refuse RF ablation was made. Complications were presented by a single case of bilateral phrenic nerve palsy, which required plication of the diaphragm, and two spontaneously resolved pulmonary atelectasis.Conclusion. The efficacy of atrial fibrillation thoracoscopic radiofrequency ablation during the follow-up period of one year was 90% regarding selective hybrid approach (thoracoscopic + catheter procedure). Procedure safety of TRFA was much lower than that of catheter ablation: the total number of small and big complications was 30%.

481 Posterior wall of left atrium and pulmonary veins refractory period is related to atrial fibrillation inducibility in pigs

EP Europace ◽  
2005 ◽  
Vol 7 (Supplement_1) ◽  
pp. 108-108
Author(s):  
I. Fernandez Lozano ◽  
J.M. Escudier ◽  
J. Toquero ◽  
C. Escudero ◽  
V. Mo ivas ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Refractory Period ◽  
Pulmonary Veins ◽  
Posterior Wall

scholarly journals Electrical anatomy of the left atrium during atrial fibrillation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
P Adragao ◽  
D Nascimento Matos ◽  
F Costa ◽  
P Galvao Santos ◽  
G Rodrigues ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Left Atrium ◽  
Pulmonary Vein ◽  
Refractory Period ◽  
Cycle Length ◽  
Low Voltage ◽  
Pulmonary Veins ◽  
Density Mapping ◽  
Superior Pulmonary Vein

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Twenty years ago, pulmonary veins (PV) ostia were identified as the left atrium (LA) areas with the shortest refractory period during sinus rhythm. Pulmonary veins isolation (PVI) became standard of care, but clinical results are still suboptimal. Today, a special tool using the Carto® electroanatomical mapping (EAM) allows for AF cycle length mapping (CLM), to identify the areas in the left atria with shortest refractory period, during atrial fibrillation. Using this EAM tool, our study aimed to find the LA areas with the shortest refractory period to better recognize electrical targets for catheter ablation. Methods Retrospective analysis of an unicentric registry of individuals with symptomatic drug-refractory AF who underwent PVI with Carto® EAM. CLM was performed with a high-density mapping Pentaray® catheter before and after PVI and in 4 redo procedures. We assessed areas of short cycle length (SCL) (defined as 120 to 250ms), and their relationships with complex fractionated atrial electrograms (CFAE), and low-voltage zones (from 0.1 to 0.3mV). Results A total of 18 patients (8 men, median age 63 IQR 58-71 years) were included. Most patients presented with persistent AF (n = 12, 67%), and 4 patients (22%) had a previous PVI. The mean shortest measured cycle length in AF was 140ms (SD ±27ms). All patients presented areas of SCL located in the PVs or their insertion, 70% in the posterior/roof region adjacent to the left superior pulmonary vein (LSPV) (figure 1) and 60% in the anterior region of the right superior pulmonary vein (RSPV). These two areas remained the fastest even after PVI. The anterior mitral region rarely presented SCL (17%). SCL were related to low-voltage areas in 94% and were adjacent to CFAE. Low-voltage areas and CFAE were more frequent and had a larger LA dispersion than SCL. Conclusion   We confirmed in 3D mapping that PVs are the LA zones with shortest refractory period, not only in sinus rhythm but also during AF. The persistence of SCL areas in the border zones of the PVI lines suggest the benefit of a more extensive CLM guided ablation. Larger studies are needed. Abstract Figure 1

scholarly journals Fluid–structure interaction in a fully coupled three-dimensional mitral–atrium–pulmonary model

2021 ◽  
Author(s):  
Liuyang Feng ◽  
Hao Gao ◽  
Nan Qi ◽  
Mark Danton ◽  
Nicholas A. Hill ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Left Atrium ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Pulmonary Veins ◽  
Three Dimensional ◽  
Left Heart ◽  
Structure Interaction ◽  
Acute Mitral Regurgitation ◽  
Reversal Flow

AbstractThis paper aims to investigate detailed mechanical interactions between the pulmonary haemodynamics and left heart function in pathophysiological situations (e.g. atrial fibrillation and acute mitral regurgitation). This is achieved by developing a complex computational framework for a coupled pulmonary circulation, left atrium and mitral valve model. The left atrium and mitral valve are modelled with physiologically realistic three-dimensional geometries, fibre-reinforced hyperelastic materials and fluid–structure interaction, and the pulmonary vessels are modelled as one-dimensional network ended with structured trees, with specified vessel geometries and wall material properties. This new coupled model reveals some interesting results which could be of diagnostic values. For example, the wave propagation through the pulmonary vasculature can lead to different arrival times for the second systolic flow wave (S2 wave) among the pulmonary veins, forming vortex rings inside the left atrium. In the case of acute mitral regurgitation, the left atrium experiences an increased energy dissipation and pressure elevation. The pulmonary veins can experience increased wave intensities, reversal flow during systole and increased early-diastolic flow wave (D wave), which in turn causes an additional flow wave across the mitral valve (L wave), as well as a reversal flow at the left atrial appendage orifice. In the case of atrial fibrillation, we show that the loss of active contraction is associated with a slower flow inside the left atrial appendage and disappearances of the late-diastole atrial reversal wave (AR wave) and the first systolic wave (S1 wave) in pulmonary veins. The haemodynamic changes along the pulmonary vessel trees on different scales from microscopic vessels to the main pulmonary artery can all be captured in this model. The work promises a potential in quantifying disease progression and medical treatments of various pulmonary diseases such as the pulmonary hypertension due to a left heart dysfunction.

scholarly journals Effect of the Alterations in Contractility and Morphology Produced by Atrial Fibrillation on the Thrombosis Potential of the Left Atrial Appendage

2021 ◽  
Vol 9 ◽  
Author(s):  
Danila Vella ◽  
Alessandra Monteleone ◽  
Giulio Musotto ◽  
Giorgia Maria Bosi ◽  
Gaetano Burriesci
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Fluid Dynamic ◽  
Atrial Appendage ◽  
Primary Role ◽  
Shear Strain Rate ◽  
Increased Risk

Atrial fibrillation (AF) is a common arrhythmia mainly affecting the elderly population, which can lead to serious complications such as stroke, ischaemic attack and vascular dementia. These problems are caused by thrombi which mostly originate in the left atrial appendage (LAA), a small muscular sac protruding from left atrium. The abnormal heart rhythm associated with AF results in alterations in the heart muscle contractions and in some reshaping of the cardiac chambers. This study aims to verify if and how these physiological changes can establish hemodynamic conditions in the LAA promoting thrombus formation, by means of computational fluid dynamic (CFD) analyses. In particular, sinus and fibrillation contractility was replicated by applying wall velocity/motion to models based on healthy and dilated idealized shapes of the left atrium with a common LAA morphology. The models were analyzed and compared in terms of shear strain rate (SSR) and vorticity, which are hemodynamic parameters directly associated with thrombogenicity. The study clearly indicates that the alterations in contractility and morphology associated with AF pathologies play a primary role in establishing hemodynamic conditions which promote higher incidence of ischaemic events, consistently with the clinical evidence. In particular, in the analyzed models, the impairment in contractility determined a decrease in SSR of about 50%, whilst the chamber pathological dilatation contributed to a 30% reduction, indicating increased risk of clot formation. The equivalent rigid wall model was characterized by SSR values about one order of magnitude smaller than in the contractile models, and substantially different vortical behavior, suggesting that analyses based on rigid chambers, although common in the literature, are inadequate to provide realistic results on the LAA hemodynamics.

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