title: Rivaroxaban modulates electrical and mechanical characteristics of left atrium.
abstract: BACKGROUND
  Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear.
  
  
  RESULTS
  Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n=7) AP durations at 90% repolarization (APD90) from 76±2 to 79±3, 67±4 (P<0.05, vs. control), 59±5, (P<0.01, vs. control), and 56±4 ms (P<0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n=7) diastolic tension by 351±69 (P<0.05, vs. control), 563±136 (P<0.05, vs. control), 582±119 (P<0.05, vs. control), and 603±108 mg (P<0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 μM) and indomethacin (10 μM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n=7) diastolic tension, but shortened the APD90 from 73±2 to 60±6 ms (P<0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes.
  
  
  CONCLUSIONS
  Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, and Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsin-Lung Road Sec. 3, Taipei 116, Taiwan.
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Chang
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.forename: Jen-Hung
authors.initials: JH
authors.lastname: Huang
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D017136:Ion Transport; D008297:Male; D008839:Microelectrodes; D009025:Morpholines / Q000008:administration & dosage*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D011667:Pulmonary Veins / Q000187:drug effects / Q000503:physiopathology; D011817:Rabbits; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage*
chemical_list: D009025:Morpholines; D024642:Potassium Channels, Voltage-Gated; D013876:Thiophenes; D000069552:Rivaroxaban; D002118:Calcium