title: B-Type Natriuretic Peptide Modulates Pulmonary Vein Arrhythmogenesis: A Novel Potential Contributor to the Genesis of Atrial Tachyarrhythmia in Heart Failure.
abstract: Heart failure (HF) plays a critical role in the genesis of atrial fibrillation (AF). A high B-type natriuretic peptide (BNP) level occurs in patients with HF and in patients with AF. However, the role of BNP in the pathophysiology of AF is not clear. The purposes of this study were to evaluate the effects of BNP on pulmonary vein (PV) arrhythmogenesis.
  
  
  
  Whole-cell patch clamp and fluorescence were used to study the action potential, ionic currents, and calcium homeostasis in isolated single rabbit PV cardiomyocytes before and after a BNP infusion, with or without ODQ (10 μM), milrinone (50 μM), or ouabain (1 μM). BNP increased PV spontaneous activity by 28.2 ± 7.5% at 100 nM and by 23.8 ± 9.1% at 300 nM. Similar to those with BNP, milrinone 50 μM increased the PV beating rate from 3.0 ± 0.2 to 3.6 ± 0.3 Hz (P < 0.0005, n = 7). In the presence of ODQ application, BNP didn't change PV spontaneous activity. BNP (100 nM) increased calcium transients (F/F0from 1.6 ± 0.1 to 1.9 ± 0.2, n = 20, P < 0.05) and increased the pacemaker current (0.4 ± 0.1 to 1.0 ± 0.2 pA/pF, n = 17, P < 0.0005) in PV cardiomyocytes. Moreover, BNP (100 nM) increased the transient inward current, sodium currents, sodium-calcium exchanger currents, and L-type calcium current; but reduced late sodium currents and the Na-K pump in PV cardiomyocytes.
  
  
  
  BNP increases PV arrhythmogenesis, which may contribute to the genesis of atrial tachyarrhythmogenesis in HF. Cyclic GMP activation, phosphodiesterase 3 inhibition and Na+/K+-ATPase inhibition might participate in the BNP modulation of PV electrophysiology.
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei, Taiwan.|Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Yung-Kuo
authors: YK
authors: Lin
authors: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.
authors: Yao-Chang
authors: YC
authors: Chen
authors: Division of Nephrology, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
authors: Yi-Ann
authors: YA
authors: Chen
authors: The First Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University, Taoyuan, Taiwan.
authors: Yung-Hsin
authors: YH
authors: Yeh
authors: School of Medicine, National Yang-Ming University; Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan.
authors: Shih-Ann
authors: SA
authors: Chen
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Yi-Jen
authors: YJ
authors: Chen
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism / Q000494:pharmacology*; D011667:Pulmonary Veins / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D020097:Natriuretic Peptide, Brain; D012964:Sodium
keywords: B-type natriuretic peptide; atrial fibrillation; heart failure; pulmonary vein