Beat-to-beat variability of repolarization determines proarrhythmic outcome in dogs susceptible to drug-induced torsades de pointes

Abstract

Background: Recent results in dogs show that increased beat-to-beat variability of repolarization (BVR) predicts drug-induced torsades de pointes (TdP) more accurately than conventional measures of repolarization prolongation. We investigated whether increasing or decreasing BVR would change proarrhythmic outcome accordingly. Methods and Results: The non-cardiovascular, IKr-blocking drug sertindole (1.0 mg/kg IV) induced TdP in 10 of 13 anesthetized dogs with chronic AV block. At a lower dose (0.2 mg/kg IV) no TdP was induced, despite similar increases in QT intervals (1.0 mg/kg: 400±60 to 495±65 ms, P<0.05 (⁎); 0.2 mg/kg: 400±60 to 475±85 ms⁎).