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Cardiovascular Research 2001 50(2):335-344; doi:10.1016/S0008-6363(01)00233-4
© 2001 by European Society of Cardiology
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Copyright © 2001, European Society of Cardiology

Interactions between antiarrhythmic drugs and cardiac memory

Alexei N Plotnikov1,a, Alexei Shvilkina,1, Wen Xionga, Joris R de Grootb, Leonid Rosenshtraukhc, Steven Feinmarka, Ravil Gainullina, Peter Danilo, Jr.a and Michael R Rosena,*

aCenter for Molecular Therapeutics, Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY, USA
bExperimental and Molecular Cardiology Group, Cardiovascular Research Institute Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
cLaboratory of Heart Electrophysiology, Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia

* Corresponding author. Present address: Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, PH7West-321, New York, NY 10032, USA. Tel.: +1-212-305-8754; fax: +1-212-305-8351 mrr1{at}columbia.edu

Objective: Ventricular pacing or arrhythmias can induce cardiac memory (CM). We hypothesized that clinically administered antiarrhythmic drugs alter the expression of CM, and that the repolarization changes characteristic of CM can modulate the effects of antiarrhythmic drugs. Methods: We studied conscious, chronically-instrumented dogs paced for two 1-h periods to study the 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: Pacing, alone, for 2 h significantly prolonged ERP only near the left ventricular pacing site, whereas pacing alone for 21 days prolonged ERP at all sites (P<0.05). Quinidine and E4031, but not lidocaine, prolonged repolarization and ERP and suppressed evolution of CM in protocol 1. However, quinidine's effect in prolonging repolarization was diminished in both protocols, while its effect in prolonging ERP was diminished in the 21-day protocol only. In contrast, the effects of E4031 were additive to those of CM, prolonging repolarization and ERP in both protocols, while lidocaine showed no changes in effect at all. Conclusions: Pacing to induce CM significantly affects ventricular repolarization and refractoriness, and there are interactions between CM, quinidine and E4031. Depending on the specific drug, these interactions have the potential to be anti- or proarrhythmic, and may impact importantly on the clinical efficacy of drugs as well as on electrophysiologic testing of drug actions.

KEYWORDS Antiarrhythmic agents; ECG; K-channel; Ventricular arrhythmias

1 Contributed equally as first authors.


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