Circulation, Vol 79, 1106-1117, Copyright © 1989 by American Heart Association
DS Echt, JN Black, JT Barbey, DR Coxe and E Cato
Antiarrhythmic drugs have been reported to produce variable effects on
defibrillation energy requirements. However, the relation between the in
vitro electrophysiologic effects of these agents and the changes in
defibrillation energy requirements have not been systematically examined.
Therefore, we evaluated the effects of the sodium channel blocking drugs
lidocaine and procainamide, the action potential prolonging drugs N-acetyl
procainamide and clofilium, and the potassium current blocker cesium in
acute canine models with the same internal spring and epicardial patch
electrodes used in humans for ventricular defibrillation testing. Ten
series of experiments were performed in 78 dogs. Nonlinear regression was
used to derive curves of energy dose versus percent successful
defibrillation attempts and the 50% and 90% effective energy dose for each
experimental condition. Saline control experiments indicated that the
preparation was stable throughout the 6- hour duration of the experiments.
Lidocaine doubled the defibrillation energy requirement (p less than 0.001)
at a mean plasma concentration of 8.2 micrograms/ml. The effect of
lidocaine on defibrillation energy was reversible, present at therapeutic
plasma concentrations, linearly related to plasma concentration (r = 0.69,
p less than 0.002), and present even after only 5-second episodes of
ventricular fibrillation. In contrast, procainamide had no effect on
defibrillation energy at mean plasma concentrations of 8.5 and 13
micrograms/ml, even after prolonged (30-second) episodes of ventricular
fibrillation, whereas N- acetyl procainamide, clofilium, and cesium all
decreased the energy requirement for defibrillation by 13-27%. Moreover,
with the addition of N-acetyl procainamide, there was a trend toward
diminishing the increase in defibrillation energy requirement caused by
lidocaine. All agents prolonged the mean ventricular fibrillation cycle
length. Lidocaine shortened the QT interval, whereas all other agents
increased the QT (p less than 0.05). The major electrophysiologic effect of
lidocaine is of sodium channel blockade, whereas, N-acetyl procainamide,
clofilium, and cesium predominantly increase the action potential duration,
and procainamide exerts both effects. Thus, these data indicate that sodium
channel block and action potential prolongation exert significant and
antagonistic modulating effects on defibrillation energy requirements.
ARTICLES
Evaluation of antiarrhythmic drugs on defibrillation energy requirements in dogs. Sodium channel block and action potential prolongation
Cardiology Division, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
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