Circulation, Vol 86, 870-877, Copyright © 1992 by American Heart Association
M Talajic, R Lemery, D Roy, C Villemaire, R Cartier, B Coutu and S Nattel
BACKGROUND. Tachycardia enhances the channel-blocking effects of
antiarrhythmic drugs. In contrast to the extensive data regarding the
rate-dependent effects of sodium channel blockers in humans, little is
known about the frequency-dependent effects of calcium channel blockers on
human atrioventricular (AV) nodal properties. Accordingly, the purpose of
this study was to evaluate the importance of heart rate in modulating the
electrophysiological effects of diltiazem in humans. METHODS AND RESULTS.
Electrophysiological studies were performed in 25 patients. Sinus node,
atrial, and AV nodal function were evaluated at multiple atrial rates under
control conditions and after administration of one of three intravenous
doses of diltiazem designed to produce low, intermediate, and high stable
plasma concentrations (designated doses 1, 2, and 3, respectively). Results
were analyzed in terms of the longest and shortest cycle lengths obtainable
in each patient under control and drug conditions. Plasma concentrations of
diltiazem were stable and averaged 43 +/- 4, 73 +/- 6, and 136 +/- 11 ng/ml
for doses 1, 2, and 3, respectively. Sinus node recovery time, intra-atrial
conduction time, atrial effective refractory period, and HV interval were
unaffected by diltiazem infusion. Effects of diltiazem were limited to
changes in AV nodal parameters. Stable, dose-dependent increases in
Wenckebach cycle length were observed after all three doses of diltiazem
(increases of 54 +/- 13, 84 +/- 18, and 174 +/- 33 msec for doses 1, 2, and
3, respectively). Small nonsignificant increases in AH interval and
atrioventricular effective refractory period (AVERP) were observed after
dose 1 of diltiazem. At long cycle lengths, diltiazem caused modest
increases in AH interval (3 +/- 4 and 25 +/- 8 msec for doses 2 and 3,
respectively) and AVERP (36 +/- 12 and 70 +/- 25 msec). Drug effects were
far greater at short cycle lengths (45 +/- 17 msec, 58 +/- 12 msec for AH
interval and 80 +/- 24 msec, 163 +/- 41 msec for AVERP; p less than 0.05
versus values at long cycle lengths). At rapid rates, effects of diltiazem
on AVERP substantially exceeded those on AV conduction, a result that could
account for the beneficial effects of diltiazem during paroxysmal AV
reentrant tachycardia by decreasing the excitable gap. CONCLUSIONS.
Depressant effects of diltiazem on human AV nodal function are highly
dependent on atrial rate; the rate-dependent actions on AV nodal
refractoriness probably contribute to beneficial effects of diltiazem in
patients with supraventricular arrhythmias.
ARTICLES
Rate-dependent effects of diltiazem on human atrioventricular nodal properties
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
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