ECHANISMS responsible for cardiac arrhythmias are generally divided into three major categories: disorders of impulse formation, disorders of impulse conduction, and combinations of both causes.‘-’ Although this classification is limited and contains some inconsistencies, it serves as a useful framework in which to discuss the pathogenesis of cardiac arrhythmias. Normal automaticity refers to the normal diastolic depolarization of pacemakers found in the normal sinus node, Purkinje fibers, and in other areas of the heart. Abnormal automaticity, a disorder of impulse formation, may occur in many of these fibers, as well as in atria1 and ventricular muscle subjected to a variety of pertubations. Triggered activity, another form of abnormal impulse formation, is a transient membrane oscillation triggered by cardiac depolarization. When this oscillation occurs early, before repolarization is completed, it is called an early afterdepolarization (Fig 1). When it occurs late, after repolarization is completed, it is called a delayed afterdepolarization (Fig 2).3 Slow heart rates generally increase the amplitude of early afterdepolarizations, whereas fast heart rates, within limits, increase the amplitude of delayed afterdepolarizations. Early afterdepolarizations result from a reduced repolarizing current in comparison with the depolarizing current. This may be caused by a reduced outward current, an increased inward current, or both mechanisms.3 Because a variety of interventions that affect different currents can abolish earIy afterdepolarizations (eg, calcium channel blockers,6 sodium channel blockers,7 increasing rate or increasing external potassium concentration) and because a variety of substances that can alter different currents can produce early afterdepolarizations (eg, quinidine7 and related drugs: a sea anemone polypeptide,’ calcium current agonists,’ acidosis,” low extracellular potassium concentration,” hypoxia, and catecholamines), a diversity of currents have been suggested as causes of early afterdepolarizations. These include a calcium current through L-type calcium channels,’ the sodium “window” or slowly inactivating current,” sodium channel exchange mechanisms,13 the transient inward current activated by elevated intracellular calcium,14 intracellular potassium accumulation,*2 and the I,, current.” Cesium blocks inward rectifying potassium currents and delays repolarizatio# to produce early afterdepolarizations. However, the ionic basis of cesium-induced afterdepolarizations is still unclear. Although some early afterdepolarizations may be due to electrotonic membrane events,” a calcium current through L-type calcium channels may be involved.“” Cesium produces early afterdepolarizations in canine cardiac Purkinje fibers’9‘21 and in the intact heart.21-23 Magnesium suppresses these early afterdepolarizations and associated ventricular tachyarrhythmias,“~21 possibly by blocking the calcium current,24 whereas ansae subclaviae stimulation, infusion of norepinephrine, and selective CY- and P-agonists augment early afterdepolarizations.