Dabigatran and thrombin modulate electrophysiological characteristics of pulmonary vein and left atrium

Chien Jung Chang, Yao Chang Chen, Yu Hsun Kao, Yung Kuo Lin, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticle

17 Citations (Scopus)

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. Methods and 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 afterdepolarization 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.

Original languageEnglish
Pages (from-to)1176-1183
Number of pages8
JournalCirculation: Arrhythmia and Electrophysiology
Volume5
Issue number6
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Atrial fibrillation
  • Direct thrombin inhibitor
  • Protease-activated receptor
  • Pulmonary vein
  • Thrombin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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