• Hiroshi Morita, Douglas P Zipes, Shiho T Morita, and Jiashin Wu.
• Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
• Heart Rhythm. 2010 Jun 1;7(6):820-7.

BackgroundGenetic defects in the sodium channel or in the calcium channel have been identified in patients with Brugada syndrome (BS). However, the differences in their genotype-phenotype correlations are still unclear.ObjectiveWe evaluated the phenotypic differences and therapeutic effects between the sodium channel and calcium channel abnormalities in in vitro models of BS.MethodsWe created two models of BS in 18 isolated and arterially perfused canine right ventricular preparations: (1) sodium channel dysfunction model (Na model, n = 11) by pilsicainide and pinacidil and (2) calcium channel dysfunction model (Ca model, n = 7) by verapamil; optically mapped action potentials (APs) on their transmural surface; and evaluated APs and electrocardiograms (ECGs) at pacing cycle lengths (CLs) of 2,000 and 1,000 ms.ResultsCL = 1,000 ms: Both models had coved-type ST elevation in the ECG, longer AP duration (APD) in the epicardium than in the endocardium, and a similar incidence of spontaneous ventricular arrhythmias. However, the Ca model had a higher incidence of T wave alternans (TWA) than the Na-model. CL = 2,000 ms: ECGs of the Ca model converted to saddleback-type ST elevation with shorter APDs in the epicardium than in the endocardium, whereas the Na model still had coved-type ST elevation and longer APDs in the epicardium. None of the Ca model preparations had ventricular arrhythmias or TWA, although the Na model had frequent ventricular arrhythmias and TWA.ConclusionAlthough both sodium channel and calcium channel dysfunction produced similar BS ECGs and arrhythmogenesis at 60 bpm, calcium channel dysfunction was associated with a higher incidence of TWA at 60 bpm, less ST elevation, and fewer arrhythmias at 30 bpm compared with sodium channel dysfunction.Copyright (c) 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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