Smartest Doc
ATX-II-induced pulmonary vein arrhythmogenesis related to atrial fibrillation and long QT syndrome
European Journal of Clinical Investigation, 08/01/2012
Clinical Article
Lu YY et al. – The INa,L enhancer anemonia sulcata toxin II (ATX–II) can increase PV arrhythmogenesis, which can be attenuated or blocked by ranolazine. This suggests that atrial fibrillation (AF) may be related to type 3 Long QT syndrome (LQTS) through increased INa,L.
Methods- Conventional microelectrodes were used to record the action potentials (AP) and contractility in isolated rabbit PV specimens before and after ATX–II administration with or without ranolazine.
- Anemonia sulcata toxin II (100 nM) increased the PV spontaneous rates from 2.0 ± 0.1 to 2.9 ± 0.2 Hz (n = 7), induced PV burst firing (100%) with the genesis of early afterdepolarization (EAD) (86%) and prolonged the AP duration.
- Ranolazine (0.1, 1 and 10 μM) dose dependently reduced the PV spontaneous rates from 2.5 ± 0.2 to 2.3 ± 0.2 Hz, 1.9 ± 0.2 and 1.5 ± 0.3 Hz (P < 0.05) and decreased the diastolic tension by 40 ± 19%, 87 ± 26% and 113 ± 28%.
- In the presence of ranolazine (10 μM), ATX–II (100 nM) further increased the AP duration.
- However, ATX–II neither increased the PV spontaneous rates (1.6 ± 0.1 vs. 1.7 ± 0.2 Hz, n = 7) nor induced PV burst firing or EAD.
- Moreover, ranolazine (10 μM) reduced ATX–II–induced PV acceleration and EAD.