In ischemia, abnormal automaticity may occur in both CLINICAL STATEMENTS AND GUIDELINES ventricular myocytes and Purkinje fibers, and may also enhance normal automaticity in Purkinje fibers in the ischemic zone. 3.3. Triggered Activity Early afterdepolarizations occur during late phase 2 or early phase 3 of the action potential,S3.4-3 S3.4-5 usually in the setting of action potential prolongation due to an increase in inward currents (the late sodium cur- rent, the inward calcium current or the sodium cal- cium exchange current) or a decrease in repolarizing potassium currents. Under these conditions, early afterdepolarizations may be initiated when reacti- vation of the inward L-type calcium channel occurs before the membrane has returned to a more nega- tive potential than that required for calcium channel reactivation. Spontaneous calcium release from the sarcoplasmic reticulum may also result in activation of a depolarizing sodium/calcium exchange current. Early afterdepolarizations are the trigger for torsades de pointes VT associated with QT prolongation either induced by medications or other acquired factors or due to mutations of ion channels causing the long QT syndrome. In these cases, it is possible that the early afterdepolarization/triggered activity sequence is the trigger that culminates in polymorphic VT/VF. Delayed afterdepolarizations occur after complete membrane repolarization and develop under condi- tions of intracellular calcium overload. Factors con- tributing to elevated intracellular calcium load include tachycardia, catecholamines, hypokalemia, digoxin toxicity, cardiac hypertrophy, and HF.S3.4-6,S3.4-7 Elevated sarcoplasmic calcium content or increased sensitivity of the ryanodine receptor can initiate spontaneous calci- um release, which activates a transient inward current driven predominantly by the sodium calcium exchange current. If the membrane depolarization is sufficiently large, the inward sodium current is activated resulting in a triggered action potential. 