Abstract 1403: Interventricular Heterogeneities Underlie Electrophysiologic Manifestations in Andersen-Tawil Syndrome (LQT7)
Andersen-Tawil syndrome (ATS) is a disease associated with QT prolongation, ventricular arrhythmias and hypokalemic periodic paralysis. ATS is linked to defects in the inward rectifier potassium channel (IK1). It was demonstrated that right ventricular (RV) myocytes have significantly lower IK1 current than left (LV). We hypothesized that ECG manifestations in ATS are dependent on cellular heterogeneities between the LV and RV. Barium chloride (BaCl2, 10 microM) was perfused to reduce IK1 in isolated guinea pig whole-heart preparations (n=4) and simulate ATS. Extracellular potassium concentration varied from 2 to 6mM [K+]o. Ratiometric optical action potentials were recorded from the epicardial, anterior surface of the LV and RV. BaCl2 significantly prolonged QT interval during hypokalemia (2mM [K+]o) compared to control by 14.7±6.1% (p<0.05). RV action potential durations (APD) (figure⇓, filled circles) were significantly greater than LV (filled squares) during 2mM [K+]o perfusion (*, p<0.05). BaCl2 and 2mM [K+]o significantly increased APD in the RV(empty circles) (†, p<0.05) and LV (empty squares, ‡, p<0.05) above 2mM [K+]o alone. In the presence of BaCl2, RV APD increased by 31% (**, p<0.05) and LV by 18% (**,p<0.05) as [K+]o changed from 4 to 2mM. At 2mM [K+]o, BaCl2 increased APD dispersion between LV and RV from 12.0±1.3 to 18.33±2.3 ms. Spontaneous self-terminating arrhythmias consistently occurred (n=4) during hypokalemia (2mM [K+]o) and BaCl2 perfusion. These data suggest that RV APDs are more sensitive to changes in [K+]o, and QT prolongation is, in part, a result of disproportionate APD prolongation in RV myocytes under conditions of reduced [K+]o and IK1.