Mechanisms of drug-induced proarrhythmia in clinical practice

Figure 1 Relationship between the phases of ventricular transmembrane action potential and the surface electrocardiogram. A: A reduction of outward currents (IKr, IKs) during phase 2 and 3 leads to action potential duration (APD) prolongation and QT interval prolongation. Activation of inward depolarizing currents (ICa, INa/Ca) may then give rise to early afterdepolarizations (EADs) and torsades de pointes (TdP). B: This scheme is showing that APD prolongation caused by IKr blockade is not the sole determinant for TdP. Transmural dispersion of repolarization (TDR) is required in order to form a zone of functional refractoriness in the mid myocardial layer, which is probably the basis of the re-entry that is sustaining TdP. ECG: Electrocardiographic.