Downregulation of delayed rectifier K+ currents in dogs with chronic complete atrioventricular block and acquired torsades de pointes

Background-Acquired QT prolongation enhances the susceptibility to torsades de pointes (TdP). Clinical and experimental studies indicate ventricular a ction potential prolongation, increased regional dispersion of repolarizati on, and early afterdepolarizations as underlying factors, We examined wheth er K+-current alterations contribute to these proarrhythmic responses in an animal model of TdP: the dog with chronic complete atrioventricular block (AVB) and biventricular hypertrophy. Methods and Results-The whole-cell K+ currents I-TO1, I-Kl, I-Kr, and I-Ks were recorded in left (LV) and right (RV) ventricular midmyocardial cells f rom dogs with 9+/-1 weeks of AVB and controls with sinus rhythm. I-TO1 dens ity and kinetics and I-Kl outward current were not different between chroni c AVB and control cells. I,had a similar Voltage dependence of activation a nd time course of deactivation in chronic AVB and control. I,density was si milar in LV myocytes but smaller in RV myocytes (-45%) of chronic AVB versu s control. For I-Ks, voltage-dependence of activation and time course of de activation were similar in chronic AVB and control. However, I-Ks densities of LV (-50%) and RV (-55%) cells were significantly lower in chronic AVB t han control. Conclusions-Significant downregulation of delayed rectifier K+ current occu rs in both ventricles of the dog with chronic AVB. Acquired TdP in this ani mal model with biventricular hypertrophy is thus related to intrinsic repol arization defects.