scholarly journals Inhibition of Adenosine Pathway Alters Atrial Electrophysiology and Prevents Atrial Fibrillation

2020 ◽  
Vol 11 ◽  
Author(s):  
Luca Soattin ◽  
Anniek Frederike Lubberding ◽  
Bo Hjorth Bentzen ◽  
Torsten Christ ◽  
Thomas Jespersen
Keyword(s):  
Atrial Fibrillation ◽  
Atrial Electrophysiology

scholarly journals Altered atrial restitution dynamics and refractoriness in metabolic syndrome due to up-regulation of potassium repolarizing currents increases susceptibility to atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
C J Calvo ◽  
A Rodriguez ◽  
E Almar ◽  
O Arias ◽  
W Lozano ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Metabolic Syndrome ◽  
Computational Models ◽  
Coconut Oil ◽  
Diabetic Patients ◽  
Model Parameters ◽  
Atrial Electrophysiology ◽  
Increased Risk ◽  
In Silico Models ◽  
High Sucrose

Abstract Background Metabolic alterations, such as Metabolic Syndrome (MS), describe an association of factors including diabetes, hypertension, obesity and dyslipidemia, linked to higher risk and prevalence of overall cardiovascular disease, arrhythmogenesis and sudden cardiac death. Obese and diabetic patients have shown an increased risk for developing atrial fibrillation (AF). However, underlying mechanisms are not understood. Purpose To study the effects of MS and obesity remodeling in atrial restitution dynamics, frequency-dependent adaptation, refractoriness and its potential susceptibility to AF. Methods Electrophysiological experimental data from High-fat (HF-O, standard rabbit chow with an additional 15% fat) and Hig-fat High-Sucrose Metabolic Syndrome (HFHS-MS, 10% hydrogenated coconut oil and 5% lard, 15% high-sucrose dissolved in water) rabbit models were used to adjust computational models atrial electrophysiology remodeling under each condition. Additionally, isoproterenol and AF conditions were considered to challenge both in-silico models. Validation and sensitivity analysis were performed for each model parameters. Computational simulations in conditions of pacing at different pacing cycle lengths was assessed at 100, 125, 150, 200, 250, 350, 450, 500, 650, 750, 850, 1000 ms. Restitution dynamics were automatically determined and analyzed, as well as restitution slopes and presence of automaticity, early after-depolarizations, alternans and cardiac arrhythmia induction. Results Shortening of action potential duration and refractoriness in the left atrium was observed under HFHS-MS. Upstroke velocity, maximum excitability and sodium availability were altered both in HF-O and HFHS-MS. HF-O remodeling showed presence of alternans at high pacing frequencies. Repolarization restitution was shortened in conditions of ISO and MS-AF. Restitution slopes were >1 in HF-O and HFHS-MS, which was correlated to higher susceptibility to AF, and further increased in MS-AF. Under MS-AF, abbreviation in APD in both atria, resulted in increased reentrant frequencies in AF, which was exacerbated under IK1 up-regulation, increasing atrial vulnerability. Conclusions HFHS-MS underlies modifications in atrial electrophysiology including shorter refractoriness in HFHS-MS, as well as modifications in atrial excitability, which may be pro-arrhythmic mainly at high frequency rates. This could be explained in part by an up-regulation of outward potassium channels. These results could partially explain increased susceptibility for AF in MS. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Distinct Effects of Ibrutinib and Acalabrutinib on Mouse Atrial and Sinoatrial Node Electrophysiology and Arrhythmogenesis

2021 ◽  
Author(s):  
Jari M. Tuomi ◽  
Loryn J. Bohne ◽  
Tristan W. Dorey ◽  
Hailey J. Jansen ◽  
Yingjie Liu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Action Potential ◽  
Sinoatrial Node ◽  
Optical Mapping ◽  
Delayed Rectifier ◽  
Action Potential Firing ◽  
Atrial Electrophysiology ◽  
Potential Firing ◽  
Beating Rate ◽  
Upstroke Velocity

Background Ibrutinib and acalabrutinib are Bruton tyrosine kinase inhibitors used in the treatment of B‐cell lymphoproliferative disorders. Ibrutinib is associated with new‐onset atrial fibrillation. Cases of sinus bradycardia and sinus arrest have also been reported following ibrutinib treatment. Conversely, acalabrutinib is less arrhythmogenic. The basis for these different effects is unclear. Methods and Results The effects of ibrutinib and acalabrutinib on atrial electrophysiology were investigated in anesthetized mice using intracardiac electrophysiology, in isolated atrial preparations using high‐resolution optical mapping, and in isolated atrial and sinoatrial node (SAN) myocytes using patch‐clamping. Acute delivery of acalabrutinib did not affect atrial fibrillation susceptibility or other measures of atrial electrophysiology in mice in vivo. Optical mapping demonstrates that ibrutinib dose‐dependently impaired atrial and SAN conduction and slowed beating rate. Acalabrutinib had no effect on atrial and SAN conduction or beating rate. In isolated atrial myocytes, ibrutinib reduced action potential upstroke velocity and Na + current. In contrast, acalabrutinib had no effects on atrial myocyte upstroke velocity or Na + current. Both drugs increased action potential duration, but these effects were smaller for acalabrutinib compared with ibrutinib and occurred by different mechanisms. In SAN myocytes, ibrutinib impaired spontaneous action potential firing by inhibiting the delayed rectifier K + current, while acalabrutinib had no effects on SAN myocyte action potential firing. Conclusions Ibrutinib and acalabrutinib have distinct effects on atrial electrophysiology and ion channel function that provide insight into the basis for increased atrial fibrillation susceptibility and SAN dysfunction with ibrutinib, but not with acalabrutinib.

Atrial Electrophysiology and Mechanisms of Atrial Fibrillation

2003 ◽  
Vol 8 (1_suppl) ◽  
pp. S5-S11 ◽  
Author(s):  
Stanley Nattel
Keyword(s):  
Atrial Fibrillation ◽  
Atrial Tachycardia ◽  
Scientific Basis ◽  
Clinical Settings ◽  
Genetic Determinants ◽  
Atrial Electrophysiology ◽  
Arrhythmia Mechanisms ◽  
Fibrillatory Conduction ◽  
Insight Into

Atrial fibrillation is the most common cardiac arrhythmia in clinical practice, and its management remains challenging. A solid understanding of the scientific basis for atrial fibrillation therapy requires insight into the mechanisms underlying the arrhythmia, about which an enormous amount has been learned over the past 10 years. The basic information presently available about atrial fibrillation mechanisms is reviewed. The particular properties of normal atrial electrophysiology are discussed, including salient ionic determinants of the atrial action potential and key anatomic features. Reviewed are three crucial arrhythmia mechanisms long held to be involved in atrial fibrillation: 1) rapid ectopic activity, 2) single-circuit reentry with fibrillatory conduction, and 3) multiple-circuit reentry. The determinants of each and the evidence for their involvement in clinical and/or experimental atrial fibrillation are noted. The physiological consequences, various contributing mechanisms, and clinical implications of the role of atrial-tachycardia remodeling are analyzed. Atrial-tachycardia remodeling links the potential mechanisms of atrial fibrillation, since atrial fibrillation beginning by any mechanism is likely to cause tachycardia-remodeling and thus promote the maintenance of atrial fibrillation by multiple-circuit reentry. Atrial structural remodeling is discussed as a paradigm of atrial fibrillation in which the classic features required for reentry (reduced refractory period and reentrant wavelength) may be lacking. Finally, the importance of recent insights into potential genetic determinants of atrial fibrillation is reviewed. The classic understanding of atrial fibrillation pathophysiology saw the different possible mechanisms as being alternative and opposing hypotheses. We now consider the multiple potential mechanisms as contributing to the pathophysiology of the arrhythmia to a different extent in different clinical settings and interacting with each other in a dynamic way at various stages of the natural history in many patients. It is hoped that this improved mechanistic understanding will lead to the development of improved therapeutic options.

A Plasma-Based, Amiodarone-Impregnated Material Decreases Susceptibility to Atrial Fibrillation in a Post–Cardiac Surgery Model

2016 ◽  
Vol 11 (1) ◽  
pp. 59-63 ◽  
Author(s):  
David Schwartzman ◽  
Vinay Badhwar ◽  
Robert L. Kormos ◽  
Jason D. Smith ◽  
Phil G. Campbell ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiac Surgery ◽  
Relative Reduction ◽  
Conduction Time ◽  
Atrial Electrophysiology ◽  
Histologic Evaluation ◽  
Sinus Cycle Length ◽  
System Activation ◽  
The Impact ◽  
Post Cardiac Surgery

Objective This study aimed to test the impact of a plasma-based, material (PBM) impregnated with amiodarone on atrial electrophysiology and atrial fibrillation susceptibility in a porcine post–cardiac surgery model. Methods Ten healthy pigs underwent implantation of transvenous pacing systems, after which sterile talc was infused into the pericardial sac via a pericardiotomy. In five animals, PBM was applied to the atrial epicardial surface just before talc infusion. Electrophysiologic evaluations were performed using the pacing system immediately after chest closure and 7 days later. Atrial histologic evaluations were performed. Results Immediately after chest closure, there were no significant differences in electrophysiologic parameters between talc-only and talc + PBM animals, and atrial fibrillation was largely noninducible. On postsurgical day 7, electrophysiologic evaluation revealed significantly shorter sinus cycle length and atrioventricular nodal refractoriness among talc-only animals relative to talc + PBM animals, possibly suggesting attenuated sympathetic nervous system activation in the latter. Atrial fibrillation inducibility and duration were significantly greater among talc-only animals. No significant differences in atrial refractoriness or conduction time between groups were apparent. Histologic evaluation revealed a relative reduction in epicardial inflammation and less myolysis among talc + PBM animals. Conclusions Epicardial application of a plasma-based, amiodarone-impregnated material was associated with a significant reduction in atrial inflammation and susceptibility to fibrillation.

P3748Reproducibility of magnetocardiographic imaging of atrial electrophysiology in patients with paroxysmal atrial fibrillation and healthy subjects

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Brisinda ◽  
G L Guida ◽  
A R Sorbo ◽  
R Fenici
Keyword(s):  
Magnetic Field ◽  
Atrial Fibrillation ◽  
Paroxysmal Atrial Fibrillation ◽  
Left Atrial ◽  
Visual Analysis ◽  
The Body ◽  
P Wave ◽  
Atrial Electrophysiology ◽  
Pr Interval ◽  
Atrial Repolarization

Abstract Since tangential currents are better detectable as magnetic than electric signals at the body surface, magnetocardiographic mapping (MCG) can be more sensitive than ECG to atrial electrophysiologic alteration, such as abnormal interatrial conduction and/or dispersion of atrial repolarization, as mechanisms underlying the occurrence of paroxysmal atrial fibrillation (PAF). We had previously reported that visual analysis of the magnetic field distribution (MFD) dynamics may evidence an inversion of atrial MFD early during the P-wave suggesting atrial repolarization overlapping depolarization along the descending limb of the P-wave (Guida et al 2018). Aim of this study was to systematically evaluate the reproducibility of such observation and to evaluate the reliability of non-invasive MCG imaging of atrial electrophysiology carried out in our unshielded hospital laboratory. Methods MCG was recorded, in sinus rhythm (SR), with an unshielded 36-channel SQUID-system providing about 30–40 fT/√Hz sensitivity in bandwidth DC-250Hz (sampling frequency 1kHz). MCG data of 40 patients with PAF (PAFp) and 40 age-matched healthy controls (HC), with at least two subsequent recordings to evaluate reproducibility and optimal S/N ratio, were retrospectively analyzed. The dynamics of atrial MFD was studied, at 1 ms time resolution, to identify the onset of atrial repolarization (AR), in respect of the P-wave and PR interval duration. To localize atrial sources, the inverse solution was calculated with the Effective Magnetic Dipole (EMD) model, also after subtraction of the atrial repolarization. MCG parameters of atrial electromagnetic vector (EMV) were also calculated. The reproducibility was evaluated with the intraclass correlation coefficient (ICC). Results High resolution analysis of atrial MFD dynamics confirmed that atrial repolarization field overlaps atrial depolarization during the last third of the P-wave in most investigated subjects. Thus, subtraction of average AR MFD is necessary to discover and image the left atrial depolarization pathway. The reproducibility of MCG estimate of atrial MFD and of EMV parameters was good (average ICC >0.7). In PAFp, MCG evidenced abnormality of AR MFD consistent with dispersion of atrial repolarization (Figure 1), as previously reported with simultaneous MCG and MAP recordings (Fenici & Brisinda, 2007); however, such evaluation is reliable only with optimal S/N ratio during the PR interval. Conclusions Unshielded MCG in SR is sensitive enough to non-invasively image atrial electrophysiology. Visual analysis of atrial MFD dynamics with high temporal resolution reproductively confirmed that AR MFD initiates early, within the descending limb of the P-wave, masking the deeper magnetic field generated by left atrial depolarization currents. MCG can image abnormality of AR MFD in PAFp, suggestive of dispersion of atrial action potential duration. Quantitative estimate of atrial EMV parameters differentiates PAFp from HC.

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