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ATX‐II‐induced pulmonary vein arrhythmogenesis related to atrial fibrillation and long QT syndrome
Author(s) -
Lu YenYu,
Cheng ChenChuan,
Chen YaoChang,
Chen ShihAnn,
Chen YiJen
Publication year - 2012
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2012.02655.x
Subject(s) - ranolazine , afterdepolarization , medicine , pulmonary vein , atrial fibrillation , contractility , cardiology , electrophysiology , repolarization
Eur J Clin Invest 2012; Abstract Background Long QT syndrome (LQTS) is associated with a high incidence of atrial fibrillation (AF), but the underlying mechanisms are unclear. Pulmonary veins (PVs) play a critical role in AF genesis. Type 3 LQTS increases late sodium current (I Na,L ), which may increase PV arrhythmogenesis and AF. Therefore, this study examines PV arrhythmogenesis in anemonia sulcata toxin II (ATX‐II)‐induced type 3 LQTS and evaluates whether the I Na,L inhibitor ranolazine can suppress PV arrhythmogenesis. Materials and 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. Results 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. Conclusions The I Na,L enhancer ATX‐II can increase PV arrhythmogenesis, which can be attenuated or blocked by ranolazine. This suggests that AF may be related to type 3 LQTS through increased I Na,L .