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Cellular Basis for Complex T Waves and Arrhythmic Activity Following Combined I Kr and I Ks Block
Author(s) -
EMORI TETSURO,
ANTZELEVITCH CHARLES
Publication year - 2001
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2001.01369.x
Subject(s) - afterdepolarization , repolarization , cardiology , medicine , t wave , ventricular tachycardia , electrocardiography , electrophysiology
Combined Congenital and Acquired LQTS.Introduction: A growing number of cardiomyopathies have been shown to result in a reduction in both I Kr and I Ks , yet little is known about the electrophysiologic and ECG characteristics of combined I Kr and I Ks block. Methods and Results: To address this gap in our knowledge, transmembrane action potentials (APs) from epicardial, M, and endocardial cells were recorded simultaneously, together with a transmural ECG from arterially perfused canine left ventricular wedge preparations exposed to combined I Kr (d‐sotalol; 100 μmol/L) and I Ks (chromanol 293B; 30 to 60 μmol/L) block. Under baseline conditions, the T wave was typically upright; epicardium repolarized first, coinciding with the peak of the T wave, and the M cells repolarized last, coinciding with the end of the T wave (T end ). Complex (inverted, biphasic, and triphasic) T waves developed following combined I Kr and I Ks block. M and epicardial APs prolonged dramatically, so that the endocardial AP was now the earliest to repolarize, coinciding with the first nadir of the complex T wave. In the case of biphasic/triphasic or inverted T waves, T end coincided with repolarization of either M or epicardial cells, whichever was the last to repolarize. QT intervals prolonged from 286 ± 13 msec up to 744 ± 148 msec and transmural dispersion of repolarization (TDR) increased from 33 ± 10 msec up to 244 ± 71 msec. Early afterdepolarizations (EADs) developed in M and epicardial cells, evoking extrasystoles that precipitated polymorphic ventricular tachycardia. Acceleration‐induced EADs and T wave alternans also were observed. Conclusion: Combined I Kr and I Ks block gives rise to inverted, biphasic, and triphasic T wave morphologies, a dramatic increase in TDR, and a high incidence of EADs. The diversity of T wave morphologies derives from a preferential AP prolongation of different transmural layers leading to variation in the predominance of voltage gradients on either side of the M cell region. Our study provides direct evidence linking EADs that arise in ventricular epicardial and M cells to the triggered beats that precipitate polymorphic ventricular tachycardia. Our results also suggest possible guidelines for the estimation of TDR from complex T waves appearing in the precordial leads of the surface ECG.