title: ATX-II-induced pulmonary vein arrhythmogenesis related to atrial fibrillation and long QT syndrome.
abstract: BACKGROUND
  Long QT syndrome (LQTS) is associated with a high incidence of atrial fibrillation (AF), but the underlying mechanisms are unclear. Pulmonary veins (PVs) play a critical role in AF genesis. Type 3 LQTS increases late sodium current (I(Na,L) ), which may increase PV arrhythmogenesis and AF. Therefore, this study examines PV arrhythmogenesis in anemonia sulcata toxin II (ATX-II)-induced type 3 LQTS and evaluates whether the I(Na,L) inhibitor ranolazine can suppress PV arrhythmogenesis.
  
  
  METHODS
  Conventional microelectrodes were used to record the action potentials (AP) and contractility in isolated rabbit PV specimens before and after ATX-II administration with or without ranolazine.
  
  
  RESULTS
  Anemonia sulcata toxin II (100 nM) increased the PV spontaneous rates from 2·0 ± 0·1 to 2·9 ± 0·2 Hz (n = 7), induced PV burst firing (100%) with the genesis of early afterdepolarization (EAD) (86%) and prolonged the AP duration. Ranolazine (0·1, 1 and 10 μM) dose dependently reduced the PV spontaneous rates from 2·5 ± 0·2 to 2·3 ± 0·2 Hz, 1·9 ± 0·2 and 1·5 ± 0·3 Hz (P < 0·05) and decreased the diastolic tension by 40 ± 19%, 87 ± 26% and 113 ± 28%. In the presence of ranolazine (10 μM), ATX-II (100 nM) further increased the AP duration. However, ATX-II neither increased the PV spontaneous rates (1·6 ± 0·1 vs. 1·7 ± 0·2 Hz, n = 7) nor induced PV burst firing or EAD. Moreover, ranolazine (10 μM) reduced ATX-II-induced PV acceleration and EAD.
  
  
  CONCLUSIONS
  The I(Na,L) enhancer ATX-II can increase PV arrhythmogenesis, which can be attenuated or blocked by ranolazine. This suggests that AF may be related to type 3 LQTS through increased I(Na,L) .
authors.affiliation: Division of Cardiology, Sijhih Cathay General Hospital, Sijhih, Taiwan.
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lu
authors.forename: Chen-Chuan
authors.initials: CC
authors.lastname: Cheng
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced*; D000075224:Cardiac Conduction System Disease; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D023421:Models, Animal; D010879:Piperazines / Q000494:pharmacology; D011667:Pulmonary Veins / Q000187:drug effects*; D011817:Rabbits; D000069458:Ranolazine
chemical_list: D000083:Acetanilides; D002316:Cardiotonic Agents; D003064:Cnidarian Venoms; D004791:Enzyme Inhibitors; D010879:Piperazines; C028800:toxin II (Anemonia sulcata); D000069458:Ranolazine