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.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Huang, S. Y., Chen, Y. C., Kao, Y. H., Hsieh, M. H., Chen, Y. A., Chen, W. P., Lin, Y. K., Chen, S. A., & Chen, Y. J. (2016). Renal failure induces atrial arrhythmogenesis from discrepant electrophysiological remodeling and calcium regulation in pulmonary veins, sinoatrial node, and atria. International Journal of Cardiology, 202, 846-857. https://doi.org/10.1016/j.ijcard.2015.10.004