TY - JOUR
T1 - Dabigatran and thrombin modulate electrophysiological characteristics of pulmonary vein and left atrium
AU - Chang, Chien Jung
AU - Chen, Yao Chang
AU - Kao, Yu Hsun
AU - Lin, Yung Kuo
AU - Chen, Shih Ann
AU - Chen, Yi Jen
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - Atrial fibrillation
KW - Direct thrombin inhibitor
KW - Protease-activated receptor
KW - Pulmonary vein
KW - Thrombin
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U2 - 10.1161/CIRCEP.112.971556
DO - 10.1161/CIRCEP.112.971556
M3 - Article
C2 - 23118275
AN - SCOPUS:84873878421
SN - 1941-3149
VL - 5
SP - 1176
EP - 1183
JO - Circulation: Arrhythmia and Electrophysiology
JF - Circulation: Arrhythmia and Electrophysiology
IS - 6
ER -