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Questioning flecainide's mechanism of action in the treatment of catecholaminergic polymorphic ventricular tachycardia
Author(s) -
Williams Alan J.,
Bannister Mark L.,
Thomas N. Lowri,
Sikkel Markus B.,
Mukherjee Saptarshi,
Maxwell Chloe,
MacLeod Kenneth T.,
George Christopher H.
Publication year - 2016
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp272497
Subject(s) - flecainide , catecholaminergic polymorphic ventricular tachycardia , ryanodine receptor 2 , ryanodine receptor , pharmacology , chemistry , medicine , cardiology , receptor , atrial fibrillation
Flecainide attenuates cardiac Ca2+ cycling abnormalities in malignant catecholaminetriggered arrhythmias but its mechanism of action remains highly contentious. We read with interest the study of Yang et al. (2016) that used in silico predictions in an attempt to determine the relative contribution of block by flecainide of ryanodine receptor 2 (RyR2) and the Na+ channel to the overall therapeutic effect of this drug in catecholaminergic polymorphic ventricular tachycardia (CPVT). Flecainide’s actions were modelled by considering its inhibition of the Na+ current (INa) and RyR2 in combination and individually. The authors conclude that the effects of the drug on Na+ channels are insufficient to explain its efficacy in CPVT, while its block of RyR2 alone was as effective as the combined block of INa and RyR2. Our concerns about the usefulness of this approach are twofold: