Right-to-left frequency gradient during atrial fibrillation initiated by right atrial ectopies and its augmentation by adenosine triphosphate: Implications of right atrial fibrillation

Hasebe, Hideyuki; Yoshida, Kentaro; Iida, Masataka; Hatano, Naoki; Muramatsu, Toshiro; Aonuma, Kazutaka

doi:10.1016/j.hrthm.2015.09.030

Cited by 33 publications

(36 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the first time, we performed molecular mapping of A1R and GIRK1/4 proteins from multiple regions across the entire atria and directly correlated protein expression with functional mapping data. We found that, while GIRK1 protein expression level is similar in both human atria, A1R and GIRK4 channels are more highly expressed in the RA than LA (Figure 6), which is supported by clinical 17, 18, 31, 34 and our ex vivo functional data on RA vs. LA adenosine sensitivity. Importantly, the correlation of expression of these proteins with regions of shortest APD and AF driver locations in lateral superior/middle RA during adenosine perfusion suggests that A1R and GIRK4 expression may contribute to the molecular substrate for human AF.…”

Section: Discussionsupporting

confidence: 74%

“…Moreover, adenosine triphosphate injection was also shown to augment this RA-to-LA DF gradient by predominantly increasing the DF in the superior RA vs. LA (10.7±0.7Hz vs 7.9±1.8Hz) 34 . Atienza et al 31 reported that adenosine increased DF in RA more than LA in persistent AF patients.…”

Section: Discussionmentioning

confidence: 94%

“…Although a LA-to-RA DF gradient commonly exists in paroxysmal AF 31 , a recent clinical study reported that some AF patients may have a RA-to-LA DF gradient 34 . Moreover, adenosine triphosphate injection was also shown to augment this RA-to-LA DF gradient by predominantly increasing the DF in the superior RA vs. LA (10.7±0.7Hz vs 7.9±1.8Hz) 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies 31, 34 have suggested the presence of AF reentrant drivers localized in the RA during adenosine infusion, but the direct mechanism sustaining AF was not shown. In this study, we have located areas of highest DF in the lateral RA during adenosine-induced AF and resolved in these regions that localized reentrant drivers may sustain AF (Figures 3–5).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Adenosine-Induced Atrial Fibrillation

Csepe

Hansen

et al. 2016

Circulation

View full text Add to dashboard Cite

Background Adenosine provokes atrial fibrillation (AF) with a higher activation frequency in right atria (RA) versus left atria (LA) in patients, but the underlying molecular and functional substrates are unclear. We tested the hypothesis that adenosine-induced AF is driven by localized reentry in RA areas with highest expression of adenosine A1 receptor (A1R) and its downstream GIRK channels (IK,Ado). Methods We applied bi-atrial optical mapping and immunoblot mapping of various atrial regions to reveal the mechanism of adenosine-induced AF in explanted failing and non-failing human hearts (n=37). Results Optical mapping of coronary-perfused atria (n=24) revealed that adenosine perfusion (10–100μM) produced more significant shortening of action potential durations (APD80) in RA (from 290±45ms to 239±41ms, 17.3±10.4%; p<0.01) than LA (from 307±24ms to 286±23ms, 6.7±6.6%; p<0.01). In ten hearts, adenosine induced AF (317±116 sec) that, when sustained (≥2 min), was primarily maintained by one/two localized reentrant drivers in lateral RA. Tertiapin (10–100nM), a selective GIRK channel blocker, counteracted adenosine-induced APD shortening and prevented AF induction. Immunoblotting showed that the superior/middle lateral RA had significantly higher A1R (2.7±1.7 fold; p<0.01) and GIRK4 (1.7±0.8 fold; p<0.05) protein expression than lateral/posterior LA. Conclusions This study revealed a three-fold RA-to-LA A1R protein expression gradient in the human heart, leading to significantly greater RA vs. LA repolarization sensitivity in response to adenosine. Sustained adenosine-induced AF is maintained by reentrant drivers localized in lateral RA regions with the highest A1R/GIRK4 expression. Selective atrial GIRK channel blockade may effectively treat AF during conditions with increased endogenous adenosine.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Adenosine-Induced Atrial Fibrillation

Csepe

Hansen

et al. 2016

Circulation

View full text Add to dashboard Cite

show abstract

“…134 The clinical significance of ATP-induced AF has been investigated. 135 The presence of AF does not affect the efficacy of the P2Y 12 antagonists prasugrel and ticagrelor. 136 Articles discussing the role of adenosine in atrial arrhythmias and fibrillation have been published 137 and also the role of ATP.…”

Section: Heart Diseasesmentioning

confidence: 98%

Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

317

295

View full text Add to dashboard Cite

Abstract:There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y 1 , P2Y 12 , and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine. (Circ Res. 2017;120:207-228.

show abstract

Dapagliflozin reduces pulmonary vascular damage and susceptibility to atrial fibrillation in right heart disease

et al. 2022

View full text Add to dashboard Cite

Aims Sodium‐glucose cotransporter 2 inhibitors (SGLT2is) have made considerable progress in the field of heart failure, but their application in arrhythmia remains to be in‐depth. Right heart disease (RHD) often leads to right heart dysfunction and is associated with atrial fibrillation (AF). Here, we explored the possible electrophysiologic effect of dapagliflozin (a type of SGLT2is) in the development of AF in rats with RHD. Methods and results Rats in the experimental group were intraperitoneally injected with a single dose of 60 mg/kg monocrotaline (MCT group, n = 32) on the first day of the experiment, whereas rats in the control group were injected with vehicle (CTL group, n = 32). Rats in the treatment subgroup were treated with dapagliflozin solution orally (MCT + DAPA and CTL + DAPA groups) for a total of 4 weeks, whereas rats in the rest of subgroups were given sterile drinking water. After 4 weeks, echocardiography demonstrated that MCT group rats developed obvious pulmonary arterial hypertension and right heart dysfunction. In addition, there were also obvious inflammatory infiltration, fibrosis, and muscularization in right atrial and pulmonary arteries. The P‐wave duration (17.00 ± 0.53 ms, vs. 14.43 ± 0.57 ms in CTL; 14.00 ± 0.65 ms in CTL + DAPA; 14.57 ± 0.65 ms in MCT + DAPA; P < 0.05), RR interval (171.60 ± 1.48 ms, vs. 163.10 ± 1.10 ms in CTL; 163.30 ± 1.19 ms in CTL + DAPA; 163.10 ± 1.50 ms in MCT + DAPA; P < 0.05), Tpeak‐Tend interval (65.93 ± 2.55 ms, vs. 49.55 ± 1.71 ms in CTL; 48.27 ± 3.08 ms in CTL + DAPA; P < 0.05), and corrected QT interval (200.90 ± 2.40 ms, vs. 160.00 ± 0.82 ms in CTL; 160.40 ± 1.36 ms in CTL + DAPA; 176.6 ± 1.57 ms in MCT + DAPA; P < 0.01) were significantly prolonged in the MCT group after 4 weeks, whereas P‐wave amplitude (0.07 ± 0.0011 mV, vs. 0.14 ± 0.0009 mV in CTL; 0.14 ± 0.0011 mV in CTL + DAPA; 0.08 ± 0.0047 mV in MCT + DAPA; P < 0.05) and T‐wave amplitude (0.04 ± 0.002 mV, vs. 0.13 ± 0.003 mV in CTL; 0.13 ± 0.003 mV in CTL + DAPA; P < 0.01) were decreased, and atrial 90% action potential duration (47.50 ± 0.93 ms, vs. 59.13 ± 2.1 ms in CTL; 59.75 ± 1.13 ms in CTL + DAPA; 60.63 ± 1.07 ms in MCT + DAPA; P < 0.01) and effective refractory periods (41.14 ± 0.88 ms, vs. 62.86 ± 0.99 ms in CTL; 63.14 ± 0.67 ms in CTL + DAPA; 54.86 ± 0.70 ms in MCT + DAPA; P < 0.01) were shortened. Importantly, the inducibility rate (80%, vs. 0% in CTL; 10% in CTL + DAPA; 40% in MCT + DAPA; P < 0.05) and duration of AF (30.85 ± 22.90 s, vs. 0 ± 0 s in CTL; 0.24 ± 0.76 s in CTL + DAPA; 5.08 ± 7.92 s in MCT + DAPA; P < 0.05) were significantly increased, whereas the expression levels of cardiac ion...

show abstract

Right-to-left frequency gradient during atrial fibrillation initiated by right atrial ectopies and its augmentation by adenosine triphosphate: Implications of right atrial fibrillation

Cited by 33 publications

References 21 publications

Adenosine-Induced Atrial Fibrillation

Adenosine-Induced Atrial Fibrillation

Purinergic Signaling in the Cardiovascular System

Dapagliflozin reduces pulmonary vascular damage and susceptibility to atrial fibrillation in right heart disease

Contact Info

Product

Resources

About