IK1 blockade delayed late phase 3 repolarization and prolonged the AP, more so during low [K+]o perfusion. The preparations were stable and free of spontaneous activity. Rapid pacing (CL = 1000 ms) induced slow phase 4 diastolic depolarization (DADs) in all low [K+]o preparations and in 71% of normal [K+]o preparations after CsCl treatment. Sympathetic activation (ISP: 0.05 and 0.15 μmol/L) increased the occurrence of DADs (in 86% of the normal [K+]o preparations treated with CsCl). Prominent DADs initiated new activations. Repetitive DAD-initiated activations generated VT. VT occurrences increased with sympathetic activation (VT occurrences: 0%, 14%, and 71% at ISP concentrations of 0, 0.05, and 0.15 μmol/L, respectively). Hypokalemia promoted VT in the ATS1 preparations. DADs occurred in 0%, 25%, 100%, and 100% and VT occurred in 0%, 0%, 38%, and 100% of the low [K+]o preparations before and after CsCl (0, 5, and 10 mmol/L) and after subsequent ISP treatment, respectively. Multiple migrating foci (with endocardial preference) caused polymorphic VT. Alternating DADs at two foci with coordinated timing resulted in bidirectional VT (Fig. 10–7), which occurred in 64% of low [K+]o preparations having ISP, but not in the normal [K+]o preparations. ICaL blockade with verapamil shortened APD, eliminated the DADs and VT, and prevented their induction by burst pacing in all preparations. U waves appeared following the T waves in the ECG, forming a TU complex, after CsCl treatment in 75% and 29% of the low and normal [K+]o preparations, respectively. These U waves were associated with a significant delay in the late phase 3 repolarization of the AP and with the occurrence of DADs.5