Amplified Transmural Dispersion of Repolarization as the Basis for Arrhythmogenesis in a Canine Ventricular-Wedge Model of Short-QT Syndrome

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Abstract
Background— The short-QT syndrome is a new clinical entity characterized by corrected QT intervals Methods and Results— Transmembrane action potentials from epicardial and M regions, 4 transmural unipolar electrograms, and a pseudo-ECG were simultaneously recorded in canine arterially perfused left ventricular wedge preparations. At a basic cycle length of 2000 ms, pinacidil (2 to 3 μmol/L) abbreviated the QT interval from 303.7±5.4 to 247.3±6.9 ms (mean±SEM, Pmax) increased from 27.0±3.8 to 64.9±9.2 ms (PPmax (from 55.4±13.7 to 69.7±8.3 ms), and more enduring pVT. TDRmax was correlated significantly with the Tpeak-Tend interval under all conditions. The effects of pinacidil were completely reversed by glybenclamide (10 μmol/L, n=4) and partially reversed by E4031 (5 μmol/L, n=5), which prevented induction of pVT in 3 of 5 preparations. Conclusions— Our data suggest that heterogeneous abbreviation of the action potential duration among different cell types spanning the ventricular wall creates the substrate for the genesis of VT under conditions associated with short QT intervals.