(Circulation. 1999;100:2455.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Downregulation of Delayed Rectifier K+ Currents in Dogs With Chronic Complete Atrioventricular Block and Acquired Torsades de Pointes
From the Department of Cardiology (P.G.A.V., M.A.V., R.L.H.M.G.S., J.D.M.L., H.J.J.W.), Cardiovascular Research Institute Maastricht (E.C.), Maastricht University, the Netherlands, and the Laboratory of Experimental Cardiology, University of Leuven, Belgium (K.R.S.).
Correspondence to Paul G.A. Volders, MD, PhD, Department of Cardiology, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, PO Box 5800, 6202 AZ, Maastricht, Netherlands. E-mail p.volders{at}cardio.azm.nl
Background—Acquired QT prolongation enhances the susceptibility to torsades de pointes (TdP). Clinical and experimental studies indicate ventricular action potential prolongation, increased regional dispersion of repolarization, and early afterdepolarizations as underlying factors. We examined whether 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 ITO1, IK1, IKr, and IKs were recorded in left (LV) and right (RV) ventricular midmyocardial cells from dogs with 9±1 weeks of AVB and controls with sinus rhythm. ITO1 density and kinetics and IK1 outward current were not different between chronic AVB and control cells. IKr had a similar voltage dependence of activation and time course of deactivation in chronic AVB and control. IKr density was similar in LV myocytes but smaller in RV myocytes (-45%) of chronic AVB versus control. For IKs, voltage-dependence of activation and time course of deactivation were similar in chronic AVB and control. However, IKs densities of LV (-50%) and RV (-55%) cells were significantly lower in chronic AVB than control.
Conclusions—Significant downregulation of delayed rectifier K+ current occurs in both ventricles of the dog with chronic AVB. Acquired TdP in this animal model with biventricular hypertrophy is thus related to intrinsic repolarization defects.
Key Words: electrophysiology • ventricles • torsades de pointes • myocytes • ions
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