scholarly journals β1-Adrenergic and M2 Muscarinic Autoantibodies and Thyroid Hormone Facilitate Induction of Atrial Fibrillation in Male Rabbits

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Hongliang Li ◽  
Taylor Murphy ◽  
Ling Zhang ◽  
Bing Huang ◽  
Vineet Veitla ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Thyroid Hormone ◽  
Muscarinic Receptors ◽  
Refractory Period ◽  
Electrophysiological Study ◽  
Subsequent Treatment ◽  
Effective Refractory Period ◽  
Activating Autoantibodies ◽  
The Impact ◽  
M2 Muscarinic Receptors

Abstract Activating autoantibodies to the β1-adrenergic and M2 muscarinic receptors are present in a very high percentage of patients with Graves' disease and atrial fibrillation (AF). The objective of this study was to develop a reproducible animal model and thereby to examine the impact of these endocrine-like autoantibodies alone and with thyroid hormone on induction of thyroid-associated atrial tachyarrhythmias. Five New Zealand white rabbits were coimmunized with peptides from the second extracellular loops of the β1-adrenergic and M2 muscarinic receptors to produce both sympathomimetic and parasympathomimetic antibodies. A catheter-based electrophysiological study was performed on anesthetized rabbits before and after immunization and subsequent treatment with thyroid hormone. Antibody expression facilitated the induction of sustained sinus, junctional and atrial tachycardias, but not AF. Addition of excessive thyroid hormone resulted in induced sustained AF in all animals. AF induction was blocked acutely by the neutralization of these antibodies with immunogenic peptides despite continued hyperthyroidism. The measured atrial effective refractory period as one parameter of AF propensity shortened significantly after immunization and was acutely reversed by peptide neutralization. No further decrease in the effective refractory period was observed after the addition of thyroid hormone, suggesting other cardiac effects of thyroid hormone may contribute to its role in AF induction. This study demonstrates autonomic autoantibodies and thyroid hormone potentiate the vulnerability of the heart to AF, which can be reversed by decoy peptide therapy. These data help fulfill Witebsky's postulates for an increased autoimmune/endocrine basis for Graves' hyperthyroidism and AF.

scholarly journals Angiotensin-(1–7) attenuates atrial tachycardia-induced sympathetic nerve remodeling

2017 ◽  
Vol 18 (3) ◽  
pp. 147032031772928 ◽  
Author(s):  
Wenfeng Shangguan ◽  
Wen Shi ◽  
Guangping Li ◽  
Yuanyuan Wang ◽  
Jian Li ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Tyrosine Hydroxylase ◽  
Sympathetic Nerve ◽  
Refractory Period ◽  
Atrial Tachycardia ◽  
Effective Refractory Period ◽  
Sympathetic Nerve Stimulation ◽  
Atrial Effective Refractory Period

Introduction: The effect of Angiotensin-(1–7) (Ang-(1–7)) on atrial autonomic remodeling is still unknown. We hypothesized that Ang-(1–7) could inhibit sympathetic nerve remodeling in a canine model of chronic atrial tachycardia. Materials and methods: Eighteen dogs were randomly assigned to sham group, pacing group and Ang-(1–7) group. Rapid atrial pacing was maintained for 14 days in the pacing and Ang-(1–7) groups. Ang-(1–7) was administered intravenously in the Ang-(1–7) group. The atrial effective refractory period and atrial fibrillation inducibility level were measured at baseline and under sympathetic nerve stimulation after 14 days of measurement. The atrial sympathetic nerves labeled with tyrosine hydroxylase were detected using immunohistochemistry and Western blotting, and tyrosine hydroxylase and nerve growth factor mRNA levels were measured by reverse transcription polymerase chain reaction. Results: Pacing shortened the atrial effective refractory period and increased the atrial fibrillation inducibility level at baseline and under sympathetic nerve stimulation. Ang-(1–7) treatment attenuated the shortening of the atrial effective refractory period and the increase in the atrial fibrillation inducibility level. Immunohistochemistry and Western blotting showed sympathetic nerve hyperinnervation in the pacing group, while Ang-(1–7) attenuated sympathetic nerve proliferation. Ang-(1–7) alleviated the pacing-induced increases in tyrosine hydroxylase and nerve growth factor mRNA expression levels. Conclusion: Ang-(1–7) can attenuate pacing-induced atrial sympathetic hyperinnervation.

scholarly journals Activating autoantibodies to the β1/2-adrenergic and M2 muscarinic receptors associate with atrial tachyarrhythmias in patients with hyperthyroidism

Endocrine ◽  
2014 ◽  
Vol 49 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Allison Galloway ◽  
Hongliang Li ◽  
Megan Vanderlinde-Wood ◽  
Muneer Khan ◽  
Alexandria Benbrook ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Atrial Tachyarrhythmias ◽  
Activating Autoantibodies ◽  
M2 Muscarinic Receptors

scholarly journals Functional mathematical model of dual pathway AV nodal conduction

2011 ◽  
Vol 300 (4) ◽  
pp. H1393-H1401 ◽  
Author(s):  
A. M. Climent ◽  
M. S. Guillem ◽  
Y. Zhang ◽  
J. Millet ◽  
T. N. Mazgalev
Keyword(s):  
Atrial Fibrillation ◽  
Mathematical Model ◽  
Refractory Period ◽  
Effective Refractory Period ◽  
Atrial Pacing ◽  
Wave Fronts ◽  
Av Node ◽  
Inferior Margin ◽  
His Bundle ◽  
Av Conduction

Dual atrioventricular (AV) nodal pathway physiology is described as two different wave fronts that propagate from the atria to the His bundle: one with a longer effective refractory period [fast pathway (FP)] and a second with a shorter effective refractory period [slow pathway (SP)]. By using His electrogram alternance, we have developed a mathematical model of AV conduction that incorporates dual AV nodal pathway physiology. Experiments were performed on five rabbit atrial-AV nodal preparations to develop and test the presented model. His electrogram alternances from the inferior margin of the His bundle were used to identify fast and slow wave front propagations. The ability to predict AV conduction time and the interaction between FP and SP wave fronts have been analyzed during regular and irregular atrial rhythms (e.g., atrial fibrillation). In addition, the role of dual AV nodal pathway wave fronts in the generation of Wenckebach periodicities has been illustrated. Finally, AV node ablative modifications have been evaluated. The model accurately reproduced interactions between FP and SP during regular and irregular atrial pacing protocols. In all experiments, specificity and sensitivity higher than 85% were obtained in the prediction of the pathway responsible for conduction. It has been shown that, during atrial fibrillation, the SP ablation significantly increased the mean HH interval (204 ± 39 vs. 274 ± 50 ms, P < 0.05), whereas FP ablation did not produce significant slowing of ventricular rate. The presented mathematical model can help in understanding some of the intriguing AV node mechanisms and should be considered as a step forward in the studies of AV nodal conduction.

scholarly journals Efficacy of an Adjunctive Electrophysiological Test–Guided Left Atrial Posterior Wall Isolation in Persistent Atrial Fibrillation Without a Left Atrial Low-Voltage Area

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Hirosuke Yamaji ◽  
Shunichi Higashiya ◽  
Takashi Murakami ◽  
Kazuyoshi Hina ◽  
Hiroshi Kawamura ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Refractory Period ◽  
Left Atrial ◽  
Low Voltage ◽  
Survival Curve ◽  
Posterior Wall ◽  
Effective Refractory Period ◽  
Control Group ◽  
Recurrence Rates ◽  
Free Survival

Background: Electrical remodeling precedes structural remodeling. In adjunctive left atrial (LA) low-voltage area (LVA) ablation to pulmonary vein isolation of atrial fibrillation (AF), LA areas without LVA have not been targeted for ablation. We studied the effect of adjunctive LA posterior wall isolation (PWI) on persistent AF without LA-LVA according to electrophysiological testing (EP test). Methods: We examined consecutive patients with persistent AF with (n=33) and without (n=111) LA-LVA. Patients without LA-LVA were randomly assigned to EP test–guided (n=57) and control (n=54) groups. In the EP test–guided group, an adjunctive PWI was performed in those with positive results (PWI subgroup; n=24), but not in those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, effective refractory period>20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia (AT) during measurements. LVA ablation was performed in the patients with LA-LVA. Results: During the follow-up period (62±33 weeks), the EP test–guided group had significantly lower recurrence rates (19%,11/57 versus 41%, 22/54, P =0.012) and higher Kaplan-Meier AF/AT–free survival curve rates than the control group ( P =0.01). No significant differences in the recurrence and AF/AT–free survival curve rates between the PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test–guided group. A stepwise Cox proportional hazard analyses identified EP test–guided ablation as a factor reducing the recurrence rate. The recurrence rates in the LA-LVA ablation group and EP test–guided group were similar. Conclusions: This pilot study proposed that an EP test–guided adjunctive PWI of persistent AF without LA-LVA potentially reduced AF/AT recurrences. The results suggest that there is an AF substrate in the LA with altered electrophysiological function even when there is no LA-LVA. Graphic Abstract: A graphic abstract is available for this article.

The surgical treatment of atrial fibrillation: The importance of tissue geometry and effective refractory period

2004 ◽  
Vol 199 (3) ◽  
pp. 30
Author(s):  
Gregory D. Byrd ◽  
Sandip M. Prasad ◽  
Richard B. Schuessler ◽  
John P. Boineau ◽  
Ralph J. Damiano
Keyword(s):  
Atrial Fibrillation ◽  
Surgical Treatment ◽  
Refractory Period ◽  
Effective Refractory Period ◽  
Tissue Geometry

scholarly journals Relationship between effective refractory period and inducibility of atrial fibrillation from the superior vena cava after pulmonary vein isolation

2021 ◽  
Author(s):  
Yasunobu Yamagishi ◽  
Yasushi Oginosawa ◽  
Yoshihisa Fujino ◽  
Keishiro Yagyu ◽  
Taro Miyamoto ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Vein ◽  
Superior Vena Cava ◽  
Pulmonary Vein Isolation ◽  
Refractory Period ◽  
Superior Vena ◽  
Three Dimensional ◽  
Vena Cava ◽  
Effective Refractory Period ◽  
Electrical Stimuli

Background: In terms of the pulmonary vein (PV), atrial fibrillation (AF) patients have a shorter effective refractory period (ERP) and a larger dispersion of the ERP than patients without AF. Although the frequency of AF from the superior vena cava (SVC) was the highest among non-PV foci, the characteristics of the ERP in the SVC (SVC-ERP) were unclear. The purpose of this study was to elucidate the relationship between SVC-ERP and the inducibility of AF after pulmonary vein isolation (PVI). Methods and Results: Consecutive 28 patients who underwent PVI were included. After successful PVI, the SVC-ERP was measured at three positions in SVC. Rapid electrical stimuli were delivered at the shortest SVC-ERP to induce AF. Patients in whom AF was induced were assigned to the SVC-induced group (SIG) and the remaining patients were the non-SVC-induced group (non-SIG). The size of the SVC sleeve was evaluated using three-dimensional electroanatomic mapping. The SIG had a significantly shorter average SVC-ERP (236.0±25.2 vs. 294.8±36.8 ms, p<0.001), while SVC-ERP dispersion was not significantly different (30.0±25.4 vs. 33.3±20.1 ms, p=0.56). Although the longer SVC diameter was significantly longer in the SIG (27.4±4.3 vs. 22.9±4.6 mm, p=0.03), the SVC-ERP was significantly associated with pacing inducibility of AF after adjustment for the longer SVC diameter (odds ratio: 0.96 [1-ms increments], p=0.01). Conclusions: The SIG had a shorter SVC-ERP, while the dispersion was not significantly different between the two groups. The SVC-ERP can be one of the mechanisms of arrhythmogenicity for AF originating from the SVC.

scholarly journals Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model

2021 ◽  
Author(s):  
Ryo Nishinarita ◽  
Shinichi Niwano ◽  
Hiroe Niwano ◽  
Hironori Nakamura ◽  
Daiki Saito ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Conduction Velocity ◽  
Refractory Period ◽  
Interstitial Fibrosis ◽  
Sglt2 Inhibitor ◽  
Effective Refractory Period ◽  
Control Group ◽  
Atrial Remodeling ◽  
Atrial Pacing ◽  
Atrial Effective Refractory Period

Background Recent clinical trials have demonstrated the possible pleiotropic effects of SGLT2 (sodium–glucose cotransporter 2) inhibitors in clinical cardiovascular diseases. Atrial electrical and structural remodeling is important as an atrial fibrillation (AF) substrate. Methods and Results The present study assessed the effect of canagliflozin (CAN), an SGLT2 inhibitor, on atrial remodeling in a canine AF model. The study included 12 beagle dogs, with 10 receiving continuous rapid atrial pacing and 2 acting as the nonpacing group. The 10 dogs that received continuous rapid atrial pacing for 3 weeks were subdivided as follows: pacing control group (n=5) and pacing+CAN (3 mg/kg per day) group (n=5). The atrial effective refractory period, conduction velocity, and AF inducibility were evaluated weekly through atrial epicardial wires. After the protocol, atrial tissues were sampled for histological examination. The degree of reactive oxygen species expression was evaluated by dihydroethidium staining. The atrial effective refractory period reduction was smaller ( P =0.06) and the degree of conduction velocity decrease was smaller in the pacing+CAN group compared with the pacing control group ( P =0.009). The AF inducibility gradually increased in the pacing control group, but such an increase was suppressed in the pacing+CAN group ( P =0.011). The pacing control group exhibited interstitial fibrosis and enhanced oxidative stress, which were suppressed in the pacing+CAN group. Conclusions CAN and possibly other SGLT2 inhibitors might be useful for preventing AF and suppressing the promotion of atrial remodeling as an AF substrate.

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