Interactions between antiarrhythmic drugs and cardiac memory

Objective: Ventricular pacing or arrhythmias can induce cardiac memory (CM) . We hypothesized that clinically administered antiarrhythmic drugs alter t he expression of CM, and that the repolarization changes characteristic of CM can modulate the effects of antiarrhythmic drugs. Methods: We studied co nscious, chronically-instrumented dogs paced for two l-h periods to study t he effects of drugs on the evolution of memory (protocol 1) or for 21 days (protocol 2) to observe the effects of steady-state memory on drug actions. Dogs were treated in both settings with quinidine, lidocaine or E4031, in random order. and within therapeutic serum concentration ranges. Results: P acing, alone, for 2 h significantly prolonged ERP only near the left ventri cular pacing site. whereas pacing alone for 21 days prolonged ERP at all si tes (P <0.05). Quinidine and E4031, but not lidocaine, prolonged repolariza tion and ERP and suppressed evolution of CM in protocol 1. However, quinidi ne's effect in prolonging repolarization was diminished in both protocols. while its effect in prolonging ERP was diminished in the 21-day protocol on ly. In contrast, the effects of E4031 were additive to those of CM, prolong ing repolarization and ERP in both protocols, while lidocaine showed no cha nges in effect at all. Conclusions: Pacing to induce CM significantly affec ts ventricular repolarization and refractoriness, and there are interaction s between CM, quinidine and E4031. Depending on the specific drug, these in teractions have the potential to be anti- or proarrhythmic, and may impact importantly on the clinical efficacy of drugs as well as on electrophysiolo gic testing of drug actions. (C) 2001 Elsevier Science B.V. All rights rese rved.