title: Early after/depolarizations and triggered activity: mechanisms and autonomic regulation.
abstract: An early after/depolarization (EAD) is an abnormality of the repolarization process of an action potential which causes an interruption or a retardation of normal repolarization. Two types were described: phase 3 EADs occur at a takeoff potential of approximately-60 mV and phase 2 EADs occur at the end of a prolonged plateau at a takeoff potential of between-10 and-30 mV. EADs can result from an increase in inward current, a reduction of outward current or both. EADs show cycle-length dependence: as cycle length increases and repolarization lengthens, EADs occur, and their magnitude increases, at a critical cycle length, can trigger the action potential of these EADs. The autonomic nervous system can also modulate EADs and trigger activity. In cesium-intoxicated Purkinje fibers, beta-adrenergic stimulation increases EAD magnitude and the occurrence of triggered activity. Cholinergic stimulation decreases EAD magnitude and suppresses triggered activity occurring after beta-adrenergic stimulation. Alpha 1-adrenergic stimulation has no effect on phase 3 EADs but induces phase 2 EADs. In normal Tyrode's solution (0 cesium), phenylephrine prolongs action potential and induces EADs. This effect seems to depend on alpha 1 A stimulation. These electrogenic abnormalities are supposed to be responsible for long QT and torsades de pointes. As our experimental data have shown that both the rate of stimulation and the autonomic nervous system could modulate EADs and trigger activity, we can speculate on the therapeutic implications of such modulations and the role of pacing as well as alpha- and beta-adrenergic antagonists.
authors.affiliation: Laboratoire de Cardiologie, URA CNRS 1340, Hôpital G et R Laennec, CHU de Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Charpentier
authors.forename: E
authors.initials: E
authors.lastname: Drouin
authors.forename: C
authors.initials: C
authors.lastname: Gauthier
authors.forename: H
authors.initials: H
authors.lastname: Le Marec
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000503:physiopathology*; D006801:Humans