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Europace 2000 2(4):277-285; doi:10.1053/eupc.2000.0114
© 2000 by European Society of Cardiology
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REVIEW

Rate dependence of the effect of antiarrhythmic drugs delaying cardiac repolarization: an overview

Paul Dorian and David Newman

Division of Cardiology, St Michael's Hospital Toronto, Ontario, Canada

Prolongation of the cardiac action potential and refractoriness (class III effect) is a potentially beneficial electrophysiological mechanism of action. However, this effect may be diminished or eliminated at rapid heart rates, so-called ‘reverse rate dependence’ of prolongation of repolarization.

Action potential duration normally shortens as heart rate increases, due to increases in outward repolarizing currents, and/or decreases in inward depolarizing currents. The assessment of the effect of drugs on action potential duration is complicated by inter-species differences in ionic currents mediating repolarization, heterogeneity within the heart in repolarizing currents, and differential effect of drugs in different species, during differing experimental conditions, and at different rates of stimulation.

In general, most drugs which predominantly block the IKrrepolarizing current exhibit reverse rate-dependent effects on cardiac repolarization. Drugs or combinations of drugs which produce multiple ionic channel blocks and possibly those which block the IKscurrent, may be less prone to this potentially undesirable effect.

Key Words: Antiarrhythmic agents, refractory periods, rate dependence

Correspondence: Dr P. Dorian, Division of Cardiology, St Michael's Hospital, 30 Bond Street, Room 7-051Q, Toronto, Ontario, Canada, M5B 1W8.


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