title: Dabigatran and thrombin modulate electrophysiological characteristics of pulmonary vein and left atrium.
abstract: BACKGROUND
  Dabigatran reduces stroke in atrial fibrillation. Pulmonary veins (PVs) and left atrium (LA) play a critical role in the pathophysiology of atrial fibrillation. We investigated the effects of thrombin, blood clot solution, and dabigatran on PVs and LA.
  
  
  RESULTS
  Conventional microelectrodes were used to record the action potentials in isolated PV and LA preparations before and after the administration of thrombin or blood clot solution in control and dabigatran-treated rabbits. Thrombin (0.01, 0.1, and 1 unit/mL), respectively, reduced the PV (n=6) spontaneous beating rates from 1.9±0.2 to 1.7±0.2, 1.6±0.2, and 1.4±0.3 Hz (P=0.046). Blood clot solution (0.5% and 5.0%), respectively, reduced the PV (n=5) spontaneous beating rates from 2.0±0.4 to 1.8±0.4 and 1.3±0.3 Hz (P=0.044). Thrombin (0.01, 0.1, and 1 unit/mL) and blood clot solution (0.5% and 5.0%) increased LA diastolic tension and the resting membrane potential with decreased action potential duration and contractility. Thrombin (0.01, 0.1, and 1 unit/mL) and blood clot solution (0.5% and 5%) induced delayed after depolarization and burst firing in PVs, but not in LA. N(G)-nitro-l-arginine methyl ester (100 μmol/L) or a protease-activated receptor type 1 blocker (BMS 200261, 1 μmol/L) attenuated the effects of thrombin and blood clot solution in PVs and LA. Dabigatran-treated PVs had slower spontaneous activity (1.1±0.1 Hz; n=10; P=0.0001 versus control). Their electrophysiological characteristics were not changed by thrombin (1 unit/mL) and blood clot solution (5%).
  
  
  CONCLUSIONS
  Thrombin modulates PV and LA electric and mechanical characteristics, which were blocked by dabigatran.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Chang
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
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 / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D016275:Atrial Function / Q000187:drug effects* / Q000502:physiology*; D001562:Benzimidazoles / Q000494:pharmacology*; D003029:Coagulants / Q000494:pharmacology; D000069604:Dabigatran; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology; D006490:Hemostatics / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D011667:Pulmonary Veins / Q000187:drug effects* / Q000502:physiology*; D011817:Rabbits; D044463:Receptor, PAR-1 / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D003029:Coagulants; D006490:Hemostatics; D044463:Receptor, PAR-1; D015091:beta-Alanine; D009569:Nitric Oxide; D013917:Thrombin; D000069604:Dabigatran