scholarly journals Ultrastructural and Functional Remodeling of the Coupling Between Ca 2+ Influx and Sarcoplasmic Reticulum Ca 2+ Release in Right Atrial Myocytes From Experimental Persistent Atrial Fibrillation

2009 ◽  
Vol 105 (9) ◽  
pp. 876-885 ◽  
Author(s):  
Ilse Lenaerts ◽  
Virginie Bito ◽  
Frank R. Heinzel ◽  
Ronald B. Driesen ◽  
Patricia Holemans ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sarcoplasmic Reticulum ◽  
Persistent Atrial Fibrillation ◽  
Right Atrial ◽  
Atrial Myocytes ◽  
Functional Remodeling

Natriuretic peptides and right atrial fibrosis in patients with paroxysmal versus persistent atrial fibrillation

Peptides ◽  
2010 ◽  
Vol 31 (8) ◽  
pp. 1531-1539 ◽  
Author(s):  
Hailong Cao ◽  
Lei Xue ◽  
Yanhu Wu ◽  
Hongtai Ma ◽  
Liang Chen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Natriuretic Peptides ◽  
Persistent Atrial Fibrillation ◽  
Right Atrial ◽  
Atrial Fibrosis

Abstract 15570: Direct Evidence of Endo-Epicardial Dissociation of the Atrial Wall in Patients With Longstanding Persistent Atrial Fibrillation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Natasja de Groot ◽  
Lisette vd Does ◽  
Ameeta Yaksh ◽  
Paul Knops ◽  
Pieter Woestijne ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Direct Evidence ◽  
Persistent Atrial Fibrillation ◽  
Right Atrial ◽  
Electrode Arrays ◽  
Atrial Wall ◽  
Ablative Therapies ◽  
Epicardial Layer ◽  
Right Atrial Appendage ◽  
The Right

Introduction: Transition of paroxysmal to longstanding persistent atrial fibrillation (LsPAF) is associated with progressive longitudinal dissociation in conduction and a higher incidence of focal fibrillation waves. The aim of this study was to provide direct evidence that the substrate of LsPAF consists of an electrical double-layer of dissociated waves, and that focal fibrillation waves are caused by endo-epicardial breakthrough. Hypothesis: LsPAF in humans is caused by electrical dissociation of the endo- and epicardial layer. Methods: Intra-operative mapping of the endo- and epicardial right atrial wall was performed in 9 patients with induced (N=4), paroxysmal (N=1), persistent (N=2) or longstanding-persistent AF (N=2). A clamp of two rectangular electrode-arrays (128 electrodes; inter-electrode distance 2mm) was introduced through an incision in the right atrial appendage. Series of 10 seconds of AF were analyzed and the incidence of endo-epicardial dissociation (≥15ms) was determined for all 128 endo-epicardial recording sites. Results: In patients with LsPAF the averaged degree of endo-epicardial dissociation was highest (24.9% vs. 5.9%). Using strict criteria for breakthrough (presence of an opposite wave within 4mm and <15ms before the origin of the focal wave), the far majority (77%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. Conclusions: During LsPAF considerable differences in activation of the right endo- and epicardial wall exist. Endo-epicardial fibrillation waves that are out of phase, may conduct transmurally and create breakthrough waves in the opposite layer. This may explain the high persistence of AF and the low succes rate of ablative therapies in patients with LsPAF.

Abstract 84: Atrial Fibrillation Causes a Progressive, Time-Dependent Reduction in Myocardial Neuronal NOS in Humans and Goats: Implications for AF-Induced Electrical Remodeling

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Svetlana Reilly ◽  
Xing Liu ◽  
Raja Jayaram ◽  
Sunder Verheule ◽  
Uli Schotten ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Electrical Properties ◽  
Tissue Concentration ◽  
Specific Effect ◽  
Right Atrial ◽  
Early Event ◽  
Atrial Myocytes ◽  
History Of ◽  
Neuronal Nos ◽  
The Difference

Rationale: Nitric oxide (NO) plays a key role in the regulation of cardiac and endothelial function and thrombogenesis. Atrial fibrillation (AF) has been associated with reduced NO availability but the mechanisms and implications of this finding remain to be fully investigated. Methods and Results: We evaluated NO synthase (NOS) activity and localization in right atrial (RA) tissue from 30 patients with permanent AF (vs. 65 controls in sinus rhythm, SR), and in the RA and left atrial (LA) tissue of 48 goats after 2 weeks (2W) and 6 months (6M) of pacing-induced AF. NOS activity was uncoupled in RA tissue from patients and goats in 6M-AF, and was caused by a reduction in BH4 tissue concentration and by an increase in arginase activity (HPLC). Although BH4 and arginine supplementation re-coupled NOS, it did not abolish the difference in NOS activity between AF and SR. Immunoblotting and immunolocalization revealed a progressive reduction in bi-atrial neuronal NOS (nNOS) protein with the duration of AF (by 65% at 2W, 86% at 6M in goats and by 62% in patients with AF) and a reduction in eNOS in long-standing AF. nNOS was reduced in atrial myocytes but not in neuronal tissue. The mRNA expression of NOS (qRT-PCR) was unaltered; however, the reduction in nNOS protein in AF was associated with an increase in nNOS ubiquitination which was partially reversed by inhibition of proteosomal activity with MG132; inhibition of the autophagy-lysosomal pathway with bafilomycin A1 did not restore nNOS protein. To investigate the electrophysiological consequences of a reduced nNOS in LA and RA myocytes, we compared electrical properties of the isolated atrial myocytes from nNOS-/- mice (n=18) and their wild type (WT) littermates after nNOS inhibition with SMTC. Both nNOS gene deletion and inhibition impaired myocytes' relaxation in both RA and LA, and result in a slower rate of decay of [Ca2+]i transient in the LA myocytes only. Conclusions: A reduction in bi-atrial nNOS activity and protein level is an early event in the natural history of AF that results in a chamber-specific effect on electrical properties of the myocytes.

Abstract 3490: Mechanistic Involvement of Myeloperoxidase in the Pathogenesis of Atrial Fibrillation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Volker Rudolph ◽  
Rene Andrie ◽  
Kai Friedrichs ◽  
Tanja K Rudolph ◽  
Anna Klinke ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ex Vivo ◽  
Strong Association ◽  
Neutrophil Activation ◽  
Right Atrial ◽  
Atrial Myocytes ◽  
Knock Out ◽  
Protein Residues ◽  
Heme Enzyme ◽  
Knock Out Mice

Background: Observational clinical and ex-vivo studies have established a strong association between atrial fibrillation (AF) and inflammation. However, whether inflammation is cause or consequence of AF and which specific inflammatory mediators increase atrial susceptibility to fibrillate remain elusive. Herein, we provide evidence for mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of AF. Methods and Results: Patients with AF assessed by pacemaker interrogation not only exhibited higher circulating plasma levels of MPO (503.1 [IR:404.6 –880.7] vs. 437.8 [IR:348.9 – 488.0 pmol/l; p=0.03; n=42), they also revealed an increased MPO burden in explanted left atrial tissue as compared to patients devoid of AF. In AF-patients MPO co-localized with markedly increased formation of 3-nitro and 3-chlorotyrosin, protein oxidations known to be catalyzed by MPO. Myeloperoxidase knock-out mice, pretreated with angiotensin II infusion for 2 weeks yielding increased neutrophil activation, revealed strikingly attenuated vulnerability for AF during right atrial electrophysiological stimulation as compared to wild type mice (probability of AF-induction: 3.0 vs. 12.7%; p<0.01). Whereas the electrical homogeneity of the atrial myocytes was not altered between the groups, atria of MPO knock out mice were indicative of significantly reduced atrial fibrosis and markedly reduced formation of 3-chloro- and 3-nitrotyrosine. Conclusion: In conclusion, the current findings not only underscore the significance of neutrophil activation as a critical pathophysiological prerequisite of AF, but reveal that MPO - by oxidatively modifying protein residues and increasing fibrosis of atrial myocytes - is causally linked to the initiation and perpetuation of AF.

L-type calcium currents in atrial myocytes from patients with persistent and non-persistent atrial fibrillation

2001 ◽  
Vol 96 (2) ◽  
pp. 151-159 ◽  
Author(s):  
Marius Skasa ◽  
Eberhardt Jüngling ◽  
Eckard Picht ◽  
Friedrich Schöndube ◽  
Andreas Lückhoff
Keyword(s):  
Atrial Fibrillation ◽  
Persistent Atrial Fibrillation ◽  
Calcium Currents ◽  
Atrial Myocytes

scholarly journals Long-Standing Persistent Atrial Fibrillation Ablation: How Do You Perform? Left and Right Atrial Linear Ablation in Addition to Pulmonary Vein Isolation

2020 ◽  
Vol 33 (2) ◽  
pp. 106-114
Author(s):  
Michele Brunelli ◽  
Mark Adrian Sammut
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Vein ◽  
Pulmonary Vein Isolation ◽  
Low Voltage ◽  
Superior Vena ◽  
Pulmonary Veins ◽  
Vena Cava ◽  
Persistent Atrial Fibrillation ◽  
Right Atrial ◽  
Linear Ablation

Catheter ablation of long-standing persistent atrial fibrillation is not yet clearly defined with respect to endpoints, and different ablative strategies are offered to patients. Presented here is an approach aiming at biatrial debulking in the form of extensive linear ablation, specifically targeting areas of low-voltage complex fractionated electrograms, in addition to pulmonary vein isolation. Its main advantage is that it is not dependent on operator/system variability, since the strategy of isolating the pulmonary veins, superior vena cava and left atrial posterior wall together with achievement of bidirectional block during linear ablation provides objective endpoints that can consistently be reproduced.

Abstract 1534: Structural and Functional Remodeling of the Coupling between Sarcolemmal Ca 2+ Channels and the Ryanodine Receptor in Atrial Fibrillation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ilse Lenaerts ◽  
Virginie Bito ◽  
Patricia Holemans ◽  
Hein Heidbüchel ◽  
Karin R. Sipido ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Protein Expression ◽  
Ryanodine Receptor ◽  
Cell Voltage ◽  
Atrial Myocytes ◽  
Cell Shortening ◽  
Ventricular Cells ◽  
Functional Remodeling ◽  
T Tubules ◽  
And Control

Background: Permanent atrial fibrillation (AF) in humans has been associated with structural and electrical remodelling. Data on contractile remodelling and control of sarcoplasmic reticulum (SR) Ca 2+ release via the ryanodine receptor (RyR) in permanent AF are however limited. Methods : Ewes were atrially paced at 600 bmp for a median of 23 weeks resulting in permanent AF (mean of 89.6±6 days, N=13) and compared to matched, non-instrumented control animals (CTRL, N=17). Atrial myocytes were isolated and cell shortening (field stimulation), membrane currents (whole cell voltage clamp) and [Ca 2+ ] i (Fluo-3) were measured. Protein expression was analyzed by immunoblotting. T-tubule density was quantified from confocal Z-stack images of cells stained with di-8-ANEPPS. Data are shown as mean±SEM of at least 17 cells and 5 animals. Results: Myocyte shortening and underlying [Ca 2+ ] i transients were profoundly reduced in AF (by 54.8% and 62%, p<0.01). This reduced cell shortening could be corrected by increasing [Ca 2+ ] i during caffeine-induced Ca 2+ release from the SR (L/L 0 9.7±0.5% in AF vs. 10.8±0.5% in CTRL). SR Ca 2+ content (integrated Na + /Ca 2+ exchange current during caffeine application) was not different (CTRL 1.9±0.3 pC/pF vs. AF 2±0.4 pC/pF), but calculated fractional SR Ca 2+ release during a depolarizing step to +10 mV was reduced in AF (by 20.6%, p<0.05). Peak Ca 2+ current density was modestly decreased (at <10 mV by 23.9%, p<0.01). T-tubules were present in the CTRL atrial myocytes though their density was much lower than in ventricular cells (11.4% vs. 20.6%, p<0.05). T-tubule density was robustly reduced in AF vs. CTRL (by 45%, p<0.01) with a reduction of myocyte surface:volume ratio (by 26%, p<0.01). The organization of RyR was apparently unchanged but protein expression was reduced (by 18.6%, p<0.05). Conclusion: In permanent AF, reduced SR Ca 2+ release is a major factor in the reduced cell contraction. Loss of T-tubules contributes to uncoupling of sarcolemmal Ca 2+ channels to RyR and reduced fractional SR Ca 2+ release despite preserved SR Ca 2+ content.

scholarly journals Atrial Fibrillation Is Associated With Increased Spontaneous Calcium Release From the Sarcoplasmic Reticulum in Human Atrial Myocytes

Circulation ◽  
2004 ◽  
Vol 110 (11) ◽  
pp. 1358-1363 ◽  
Author(s):  
Leif Hove-Madsen ◽  
Anna Llach ◽  
Antoni Bayes-Genís ◽  
Santiago Roura ◽  
Enrique Rodriguez Font ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes
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