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.

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.

P2867Vildagliptin reduces inducibility of atrial fibrillation in hypertensive rats complicated with diabetes mellitus

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Soeki ◽  
K Matsumoto ◽  
D Fukuda ◽  
E Uematsu ◽  
T Matsuura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Interstitial Fibrosis ◽  
Electrophysiological Study ◽  
Atrial Remodeling ◽  
Atrial Pacing ◽  
Hypertensive Rats ◽  
Significant Difference

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, increasing the incidence of ischemic stroke. Diabetes mellitus (DM) is a predictor of stroke and thromboembolism, and it was reported to be an independent risk factor for AF. A recent study has shown that, in obese mice with diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitor prevents myocardial fibrosis, active oxygen stress, weight loss and improves myocardial hypertrophy. However, the effects of DPP-4 inhibitors on atrial remodeling associated with diabetes and atrial fibrillation have not yet been clarified. Purpose This study was performed to assess whether a DPP-4 inhibitor (vildagliptin) ameliorates atrial remodeling in spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes. Methods Rats were divided into 3 groups: SHR without DM, SHR with DM treated with vehicle and SHR-DM treated with vildagliptin (3mg/kg/day; intragastric gavage). For each group, blood pressure, blood glucose level and body weight were measured serially. Cardiac function was also evaluated by echocardiography. Then, we examined AF inducibility by intracardiac electrophysiological study and the inflammation-induced atrial remodeling by biochemical analysis after 4 weeks of treatment. Results There was no significant difference in blood pressure and blood gucose level between vehicle and vildagliptin groups. Administration of vildagliptin significantly reduced AF inducibility compared with rats with vehicle. In DM rats treated with vehicle, rapid atrial pacing promoted the gene expression of inflammatory and fibrosis-related biomarkers (TNF-α, MCP-1, collagen-1) in atrium. Vildagliptin reduced these gene expression levels. In addition, administration of vildagliptin significantly reduced the interstitial fibrosis in atrium. Conclusions DPP-4 inhibitor, vildagliptin. could prevent atrial inflammation and reduce the AF inducibility in SHR complicated with DM.

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.

Recovery of the right atrial effective refractory period after cardioversion of chronic atrial fibrillation

1999 ◽  
Vol 84 (10) ◽  
pp. 1261-1264 ◽  
Author(s):  
Yasutaka Tanabe ◽  
Masaomi Chinushi ◽  
Kohji Taneda ◽  
Satoshi Fujita ◽  
Hidehiro Kasai ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Refractory Period ◽  
Chronic Atrial Fibrillation ◽  
Effective Refractory Period ◽  
Right Atrial ◽  
The Right ◽  
Atrial Effective Refractory Period

scholarly journals Translational Studies on Anti-Atrial Fibrillatory Action of Oseltamivir by its in vivo and in vitro Electropharmacological Analyses

2021 ◽  
Vol 12 ◽  
Author(s):  
Ryuichi Kambayashi ◽  
Hiroko Izumi-Nakaseko ◽  
Ai Goto ◽  
Kazuya Tsurudome ◽  
Hironori Ohshiro ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Refractory Period ◽  
Persistent Atrial Fibrillation ◽  
Effective Refractory Period ◽  
Conduction Time ◽  
Dependent Manner ◽  
Atrial Conduction Time ◽  
Atrial Effective Refractory Period

Oseltamivir has been shown to prolong the atrial conduction time and effective refractory period, and to suppress the onset of burst pacing-induced atrial fibrillation in vitro. To better predict its potential clinical benefit as an anti-atrial fibrillatory drug, we performed translational studies by assessing in vivo anti-atrial fibrillatory effect along with in vivo and in vitro electropharmacological analyses. Oseltamivir in intravenous doses of 3 (n = 6) and 30 mg/kg (n = 7) was administered in conscious state to the persistent atrial fibrillation model dogs to confirm its anti-atrial fibrillatory action. The model was prepared by tachypacing to the atria of chronic atrioventricular block dogs for &gt; 6 weeks. Next, oseltamivir in doses of 0.3, 3 and 30 mg/kg was intravenously administered to the halothane-anesthetized intact dogs to analyze its in vivo electrophysiological actions (n = 4). Finally, its in vitro effects of 10–1,000 μM on IK,ACh, IKur, IKr, INa and ICaL were analyzed by using cell lines stably expressing Kir3.1/3.4, KV1.5, hERG, NaV1.5 or CaV1.2, respectively (n = 3 for IK,ACh and IKr or n = 6 for IKr, INa and ICaL). Oseltamivir in doses of 3 and 30 mg/kg terminated the atrial fibrillation in 1 out of 6 and in 6 out of 7 atrial fibrillation model dogs, respectively without inducing any lethal ventricular arrhythmia. Its 3 and 30 mg/kg delayed inter-atrial conduction in a frequency-dependent manner, whereas they prolonged atrial effective refractory period in a reverse frequency-dependent manner in the intact dogs. The current assay indicated that IC50 values for IK,ACh and IKr were 160 and 231 μM, respectively, but 1,000 µM inhibited INa, ICaL and IKur by 22, 19 and 13%, respectively. The extent of INa blockade was enhanced at faster beating rate and more depolarized resting membrane potential. Oseltamivir effectively terminated the persistent atrial fibrillation, which may be largely due to the prolongation of the atrial effective refractory period and inter-atrial conduction time induced by IK,ACh and IKr inhibitions along with INa suppression. Thus, oseltamivir can exert a powerful anti-atrial fibrillatory action through its ideal multi-channel blocking property; and oseltamivir would become a promising seed compound for developing efficacious and safe anti-atrial fibrillatory drugs.

Sign in / Sign up

Export Citation Format

Share Document