Shih-Yu Huang1, Yao-Chang Chen2, Yu-Hsun Kao3, Ming-Hsiung Hsieh4, Yi-Ann Chen5, Wan-Ping Chen6, Yung-Kuo Lin4, Shih-Ann Chen7, Yi-Jen Chen8. 1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan. 2. Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan. 3. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 4. Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 5. Division of Nephrology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan. 6. Department of Laboratory Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan. 7. School of Medicine, National Yang-Ming University, Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan. 8. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: a9900112@ms15.hinet.net.
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.
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.
Authors: Nisha Bansal; Leila R Zelnick; Alvaro Alonso; Emelia J Benjamin; Ian H de Boer; Rajat Deo; Ronit Katz; Bryan Kestenbaum; Jehu Mathew; Cassianne Robinson-Cohen; Mark J Sarnak; Michael G Shlipak; Nona Sotoodehnia; Bessie Young; Susan R Heckbert Journal: Clin J Am Soc Nephrol Date: 2017-08-10 Impact factor: 8.237
Authors: Pietro Scicchitano; Marco Tucci; Maria Consiglia Bellino; Francesca Cortese; Annagrazia Cecere; Micaela De Palo; Francesco Massari; Pasquale Caldarola; Francesco Silvestris; Marco Matteo Ciccone Journal: Cardiovasc Drugs Ther Date: 2021-06 Impact factor: 3.727