Introduction: I_Kr inhibitors can prolong the repolarization, and may develop trigger (premature ventricular contraction: PVC) and substrate (spatial dispersion of repolarization) for the onset of torsade de pointes (TdP). We investigated how the mode of preceding changes in the early (J-T_peak) and late (T_peak-T_end) repolarization represent the characteristics of TdP. 
Methods: Well-known torsadogenic drug hydroxychloroquine in doses of 1, 3 and 10 mg/kg/10 min was intravenously administered to the chronic atrioventricular block dogs under the monitoring of Holter electrocardiogram (n=4 for each dose).  
Results: While the low or middle dose of hydroxychloroquine did not induce TdP, the high dose induced TdP in each animal at 10.0 (#1), 8.7 (#2), 9.3 (#3) and 11.3 (#4) min after the start of administration.  The R on T-type PVCs were frequently induced in the animal #1, #2 and #3 before the onset of TdP, which was not observed in the animal #4.  The TdP spontaneously terminated in the animal #1, while it degenerated into ventricular fibrillation in the others.  The changes of J-T_peak just before the onset of PVC (#1, #2, and #3) or TdP (#4) were +37, +36, +23 and +1 ms, whereas those of T_peak-T_end were +12, +20, +22 and +89 ms, respectively. 
Discussion: The prolongation of J-T_peak may trigger R on T-type PVCs possibly through Ca²⁺ overload, whereas the prolongation of T_peak-T_end will develop the substrate for maintaining spiral reentry.