afterdepolarizations

Afterdepolarizations are abnormal depolarizations that occur during or just after repolarization of the cardiac action potential, and can act as a trigger for cardiac arrhythmias. They are typically categorized as early afterdepolarizations or delayed afterdepolarizations, depending on when they arise in relation to the action potential.

Early afterdepolarizations occur during phases 2 or 3 of the action potential, when the cell membrane remains relatively depolarized and the action potential duration is prolonged. They are favored by conditions that prolong repolarization, such as certain drugs or electrolyte disturbances, and by increased inward currents, including reactivation of L-type calcium channels and late sodium currents.

Delayed afterdepolarizations occur after repolarization, during phase 4. They are often driven by intracellular calcium overload, which can cause spontaneous calcium release from the sarcoplasmic reticulum. This release activates the inward current via the Na+/Ca2+ exchanger, producing a depolarizing impulse that can trigger ectopic beats.

Common triggers and conditions include long QT syndromes, ischemia, heart failure, and electrolyte abnormalities (notably hypokalemia and hypomagnesemia). Drugs that prolong the QT interval or affect calcium and potassium currents can promote EADs, while agents that cause Ca2+ overload can promote DADs. Digoxin toxicity is a classic cause of DADs.

Clinical significance includes the potential for EADs to initiate torsades de pointes and other polymorphic ventricular tachycardias, and for DADs to provoke focal or ventricular arrhythmias. Management focuses on removing triggers, correcting electrolytes, and addressing underlying conditions. Magnesium sulfate is commonly used for torsades de pointes; avoidance of QT-prolonging drugs and, when appropriate, antiarrhythmic therapy or device interventions may be indicated for recurrent cases.