We replicated the major electrophysiological features of ATS with cesium chloride (CsCl, at IK1 blockade concentration of 5–10 mmol/l) in 23 isolated canine left ventricular tissues perfused arterially with Tyrode's solution having normal or low potassium concentrations, [K+]o. We mapped action potentials (APs) on the cut-exposed transmural surface of the wedges in control, after CsCl, and CsCl with 0.15 μmol/l isoproterenol (CsCl + ISP). CsCl delayed late phase 3 repolarization and prolonged the duration of the AP, more so during low [K+]o perfusion. Rapid pacing induced delayed afterdepolarizations (DADs) in all low [K+]o and in 71%of normal [K+]o preparations after CsCl treatment. Addition of ISP induced DADs in all preparations. DADs originated in mid-to-endocardium, and initiated VT after CsCl + ISP. Migration of DAD–VT foci resulted in multifocal VT. Alternating DADs at 2 foci resulted in bidirectional VT. There were more foci and longer durations of VT at low [K+]o than at normal [K+]o. Delayed late phase 3 repolarization of APs and DADs generated U waves. Verapamil abolished all DADs and VT.
CsCl blockade of IK1 produced a ventricular wedge model of ATS. Suppressing IK1 generated U waves by delaying late repolarization of APs and creating DADs, and promoted polymorphic VT by triggering DADs at multiple shifting sites.