| Co-Investigator(Kenkyū-buntansha) |
OHE Tohru OKAYAMA UNIVERSITY, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (70263556)
NAKAMURA Kazufumi OKAYAMA UNIVERSITY, Graduate school of Medicine and Dentistry, Assistant, 大学院・医歯学総合研究科, 助手 (10335630)
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| Research Abstract |
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 micromol/L) and I(Ks) (chromanol 293B ; 30 to 60 micromol/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
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to repolarize, coinciding with the first nadir of the complex T wave. In the case of biphasic/triphasic or inverted T waves, Tend coincided with repolarization of either M or lepicardial 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. Less
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