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Figure 5 The mechanism responsible for the initiation of torsade de pointes (TdP). (A) An R-on-T extrasystole initiated an episode of torsade de pointes in a patient with a prolonged QT interval who was receiving sotalol. (B) Transmembrane action potentials (APs) from the epicardium (Epi) and endocardium (Endo) were simultaneously recorded together with a transmural electrocardiogram (ECG) in an arterially perfused rabbit left ventricle. dl-sotalol, an I_Kr blocker, markedly prolonged the QT interval and induced phase 2 early afterdepolarization (EAD) in the endocardium. The phase 2 EADs, in turn, produced R-on-T extrasystoles capable of initiating torsade de pointes. Reprinted from Yan et al. (35), with permission.