title: Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis.
abstract: BACKGROUND
  Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of atrial fibrillation (AF). This study investigated whether selective and non-selective NSAIDs differentially regulate the arrhythmogenesis of pulmonary veins and atria.
  
  
  METHODS
  Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial node (SAN), left atrium (LA), and right atrium (RA) preparations before and after celecoxib or indomethacin administration. A whole-cell patch clamp was used to record the sodium-calcium exchanger (NCX) current, L-type calcium current (ICa-L), and late sodium current (INa-late) before and after celecoxib administration in isolated PV cardiomyocytes.
  
  
  RESULTS
  Celecoxib (0.3, 1, and 3 μM) reduced PV spontaneous beating rates, and induced delayed afterdepolarizations and burst firings in four of eight PV preparations (50%, p<0.05). Celecoxib also reduced SAN beating rates and decreased AP durations (APDs) in RA and LA, but did not change the resting membrane potential. Indomethacin (0.3, 1, 3, and 10 μM) changed neither the PV or SAN beating rates nor RA APDs, but it reduced LA APDs. Celecoxib (3 μM) significantly increased the NCX current and decreased the ICa-L, but did not change the INa-late. Ranolazine (10 μM) suppressed celecoxib (3 μM)-induced PV burst firings in 6 (86%, p<0.05) of 7 PVs. KB-R7943 (10 μM) suppressed celecoxib (3 μM)-induced PV burst firings in 5 (71%, p<0.05) of 7 PVs.
  
  
  CONCLUSIONS
  Selective and non-selective NSAIDs differentially modulate PV and atrial electrophysiological characteristics. Celecoxib increased PV triggered activity through enhancement of the NCX current, which contributed to its arrhythmogenesis.
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; Division of Cardiology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chen-Chuan
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Ten-Fang
authors.initials: TF
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering, and Institute of Physiology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.affiliation: National Yang-Ming University, School of Medicine, Taipei, Taiwan; Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: a9900112@ms15.hinet.net.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000145:classification / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000503:physiopathology*; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018408:Patch-Clamp Techniques / Q000379:methods; D011667:Pulmonary Veins / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019831:Sodium-Calcium Exchanger
keywords: Atrial fibrillation; Atrium; Celecoxib; Indomethacin; Pulmonary vein; Ranolazine