Enhancement of delayed afterdepolarizations and triggered activity by class III antiarrhythmic drugs: Multiple effects of E-4031 and dofetilide

The effects of class III antiarrhythmic agents E-4031 and dofetilide were o n action potentials and subthreshold delayed afterdepolarizations (DADs) in duced by the cardiac glycoside acetylstrophanthidin (AS) in isolated cardia c Purkinje fibres. Action potentials were recorded from cardiac Purkinje fi bers using microelectrode techniques. E-4031 and dofelitide consistently in creased DAD amplitude, occasionally caused triggered action potentials and shortened action potential duration. The application of E-4031 without prio r AS exposure, resulted in the typical class III antiarrhythmic effects of action potential lengthening and the induction of early afterdepolarization s. These findings suggest that under our conditions of AS-induced cell Ca2 overload, the effects the "pure" class III antiarrhythmic drugs, E-4031 an d dofetilide, are markedly different from those found in non-Ca2+ loaded ce lls. This may represent an additional electrophysiological mechanism for cl ass III antiarrhythmic drug toxicity. (C) 2000 Prous Science. All rights re served.