Factor Xa inhibitors differently modulate electrical activities in pulmonary veins and the sinoatrial node

European Journal of Pharmacology
Chien-Jung ChangYi-Jen Chen

Abstract

Factor Xa inhibitors reduce stroke in patients with atrial fibrillation. Pulmonary veins (PVs) and the sinoatrial node (SAN) are crucial for genesis of atrial fibrillation. However, the electrophysiological effects of factor Xa inhibitors (edoxaban and rivaroxaban) on PVs and the SAN remain unclear. Conventional microelectrodes were used to record the action potential in isolated rabbit PVs and SAN preparations before and after administration of edoxaban (0.1, 0.3, and 1 μM) or rivaroxaban (0.01, 0.03, 0.1, and 0.3 μM). A whole-cell patch-clamp was used to record the late sodium current (INa-late) in isolated single rabbit PV cardiomyocytes. Edoxaban significantly reduced PV spontaneous beating rates at 0.3 and 1 μM (N = 6 rabbits, P < 0.05), and reduced SAN beating rates at 1 μM (N = 6, P < 0.05). Similarly, rivaroxaban reduced PV spontaneous beating rates at 0.1 and 0.3 μM (N = 7, P < 0.05), and reduced SAN beating rates at 0.3 μM (N = 6, P < 0.05). However, neither edoxaban (1 μM) nor rivaroxaban (0.3 μM) reduced PV spontaneous beating rates in the presence of 1 μM BMS200261 (an inhibitor of protease-activated receptors type 1, PAR1 inhibitor) or 10 μM ranolazine (an inhibitor of late sodium current, INa-late inhibitor). Edo...Continue Reading

Citations

Jul 18, 2020·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Felix WiedmannDierk Thomas

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