Renal failure induces atrial arrhythmogenesis from discrepant electrophysiological remodeling and calcium regulation in pulmonary veins, sinoatrial node, and atria

Shih Yu Huang, Yao Chang Chen, Yu Hsun Kao, Ming Hsiung Hsieh, Yi Ann Chen, Wan Ping Chen, Yung Kuo Lin, Shih Ann Chen, Yi Jen Chen

研究成果: 雜誌貢獻文章

10 引文 (Scopus)

摘要

Background: Renal failure (RF) increases the risk of atrial fibrillation (AF), but arrhythmogenic mechanism is unclear. The present study investigated the electrophysiological effects of RF on AF trigger (pulmonary veins, PVs) and substrate (atria) and evaluated potential underlying mechanisms. Methods: Electrocardiographic, echocardiographic, and biochemical studies were conducted in rabbits with and without antibiotic-induced mild (creatinine = 1.5-6.0 mg/dl) and advanced (creatinine > 6.0 mg/dl) RF. Conventional microelectrode techniques, western blotting, and histological examinations were performed using the isolated rabbit PV, left atrium (LA), right atrium (RA) and sinoatrial node (SAN). Results: Advanced RF rabbits (n = 18) had a higher incidence (33.3% vs. 11.1% and 0%, p <0.05) of atrial arrhythmia than mild RF (n = 18) and control (n = 18) rabbits. Advanced RF rabbits exhibited faster PV spontaneous activities, longer action potential duration (APD) in the LA, higher fibrosis in the LA, and slower SAN beating rates than control rabbits, but had a similar APD and fibrosis in the RA. Caffeine (1 mM) increased advanced RF PV arrhythmogenesis, which is blocked by flecainide (10 μM), or KB-R7943 (10 μM). Moreover, advanced RF rabbits had a higher expression of the Na+/Ca2 + exchanger, protein kinase A, phosphorylated ryanodine receptor (Serine 2808), and phosphorylated phospholamban (Serine 16) in PVs, and a higher expression of Cav 1.2 in the LA, and a lower expression of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 in the SAN. Conclusions: Advanced RF increases atrial arrhythmia by modulating the distinctive electrophysiological characteristics of the PV, LA, and SAN.
原文英語
頁(從 - 到)846-857
頁數12
期刊International Journal of Cardiology
202
DOIs
出版狀態已發佈 - 一月 1 2016

指紋

Sinoatrial Node
Pulmonary Veins
Renal Insufficiency
Heart Atria
Calcium
Rabbits
Atrial Fibrillation
Serine
Action Potentials
Cardiac Arrhythmias
Creatinine
Fibrosis
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Flecainide
Ryanodine Receptor Calcium Release Channel
Potassium Channels
Microelectrodes
Cyclic AMP-Dependent Protein Kinases
Caffeine
Western Blotting

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

引用此文

@article{a4f99468c4a642a3acce0983aede5921,
title = "Renal failure induces atrial arrhythmogenesis from discrepant electrophysiological remodeling and calcium regulation in pulmonary veins, sinoatrial node, and atria",
abstract = "Background: Renal failure (RF) increases the risk of atrial fibrillation (AF), but arrhythmogenic mechanism is unclear. The present study investigated the electrophysiological effects of RF on AF trigger (pulmonary veins, PVs) and substrate (atria) and evaluated potential underlying mechanisms. Methods: Electrocardiographic, echocardiographic, and biochemical studies were conducted in rabbits with and without antibiotic-induced mild (creatinine = 1.5-6.0 mg/dl) and advanced (creatinine > 6.0 mg/dl) RF. Conventional microelectrode techniques, western blotting, and histological examinations were performed using the isolated rabbit PV, left atrium (LA), right atrium (RA) and sinoatrial node (SAN). Results: Advanced RF rabbits (n = 18) had a higher incidence (33.3{\%} vs. 11.1{\%} and 0{\%}, p <0.05) of atrial arrhythmia than mild RF (n = 18) and control (n = 18) rabbits. Advanced RF rabbits exhibited faster PV spontaneous activities, longer action potential duration (APD) in the LA, higher fibrosis in the LA, and slower SAN beating rates than control rabbits, but had a similar APD and fibrosis in the RA. Caffeine (1 mM) increased advanced RF PV arrhythmogenesis, which is blocked by flecainide (10 μM), or KB-R7943 (10 μM). Moreover, advanced RF rabbits had a higher expression of the Na+/Ca2 + exchanger, protein kinase A, phosphorylated ryanodine receptor (Serine 2808), and phosphorylated phospholamban (Serine 16) in PVs, and a higher expression of Cav 1.2 in the LA, and a lower expression of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 in the SAN. Conclusions: Advanced RF increases atrial arrhythmia by modulating the distinctive electrophysiological characteristics of the PV, LA, and SAN.",
keywords = "Atrial fibrillation, Chronic kidney disease, Left atrium, Pulmonary vein, Sinoatrial node",
author = "Huang, {Shih Yu} and Chen, {Yao Chang} and Kao, {Yu Hsun} and Hsieh, {Ming Hsiung} and Chen, {Yi Ann} and Chen, {Wan Ping} and Lin, {Yung Kuo} and Chen, {Shih Ann} and Chen, {Yi Jen}",
year = "2016",
month = "1",
day = "1",
doi = "10.1016/j.ijcard.2015.10.004",
language = "English",
volume = "202",
pages = "846--857",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Renal failure induces atrial arrhythmogenesis from discrepant electrophysiological remodeling and calcium regulation in pulmonary veins, sinoatrial node, and atria

AU - Huang, Shih Yu

AU - Chen, Yao Chang

AU - Kao, Yu Hsun

AU - Hsieh, Ming Hsiung

AU - Chen, Yi Ann

AU - Chen, Wan Ping

AU - Lin, Yung Kuo

AU - Chen, Shih Ann

AU - Chen, Yi Jen

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Renal failure (RF) increases the risk of atrial fibrillation (AF), but arrhythmogenic mechanism is unclear. The present study investigated the electrophysiological effects of RF on AF trigger (pulmonary veins, PVs) and substrate (atria) and evaluated potential underlying mechanisms. Methods: Electrocardiographic, echocardiographic, and biochemical studies were conducted in rabbits with and without antibiotic-induced mild (creatinine = 1.5-6.0 mg/dl) and advanced (creatinine > 6.0 mg/dl) RF. Conventional microelectrode techniques, western blotting, and histological examinations were performed using the isolated rabbit PV, left atrium (LA), right atrium (RA) and sinoatrial node (SAN). Results: Advanced RF rabbits (n = 18) had a higher incidence (33.3% vs. 11.1% and 0%, p <0.05) of atrial arrhythmia than mild RF (n = 18) and control (n = 18) rabbits. Advanced RF rabbits exhibited faster PV spontaneous activities, longer action potential duration (APD) in the LA, higher fibrosis in the LA, and slower SAN beating rates than control rabbits, but had a similar APD and fibrosis in the RA. Caffeine (1 mM) increased advanced RF PV arrhythmogenesis, which is blocked by flecainide (10 μM), or KB-R7943 (10 μM). Moreover, advanced RF rabbits had a higher expression of the Na+/Ca2 + exchanger, protein kinase A, phosphorylated ryanodine receptor (Serine 2808), and phosphorylated phospholamban (Serine 16) in PVs, and a higher expression of Cav 1.2 in the LA, and a lower expression of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 in the SAN. Conclusions: Advanced RF increases atrial arrhythmia by modulating the distinctive electrophysiological characteristics of the PV, LA, and SAN.

AB - Background: Renal failure (RF) increases the risk of atrial fibrillation (AF), but arrhythmogenic mechanism is unclear. The present study investigated the electrophysiological effects of RF on AF trigger (pulmonary veins, PVs) and substrate (atria) and evaluated potential underlying mechanisms. Methods: Electrocardiographic, echocardiographic, and biochemical studies were conducted in rabbits with and without antibiotic-induced mild (creatinine = 1.5-6.0 mg/dl) and advanced (creatinine > 6.0 mg/dl) RF. Conventional microelectrode techniques, western blotting, and histological examinations were performed using the isolated rabbit PV, left atrium (LA), right atrium (RA) and sinoatrial node (SAN). Results: Advanced RF rabbits (n = 18) had a higher incidence (33.3% vs. 11.1% and 0%, p <0.05) of atrial arrhythmia than mild RF (n = 18) and control (n = 18) rabbits. Advanced RF rabbits exhibited faster PV spontaneous activities, longer action potential duration (APD) in the LA, higher fibrosis in the LA, and slower SAN beating rates than control rabbits, but had a similar APD and fibrosis in the RA. Caffeine (1 mM) increased advanced RF PV arrhythmogenesis, which is blocked by flecainide (10 μM), or KB-R7943 (10 μM). Moreover, advanced RF rabbits had a higher expression of the Na+/Ca2 + exchanger, protein kinase A, phosphorylated ryanodine receptor (Serine 2808), and phosphorylated phospholamban (Serine 16) in PVs, and a higher expression of Cav 1.2 in the LA, and a lower expression of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 in the SAN. Conclusions: Advanced RF increases atrial arrhythmia by modulating the distinctive electrophysiological characteristics of the PV, LA, and SAN.

KW - Atrial fibrillation

KW - Chronic kidney disease

KW - Left atrium

KW - Pulmonary vein

KW - Sinoatrial node

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U2 - 10.1016/j.ijcard.2015.10.004

DO - 10.1016/j.ijcard.2015.10.004

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JO - International Journal of Cardiology

JF - International Journal of Cardiology

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