Proarrhythmic and antiarrhythmic effects of flecainide on nonsustained reentry around the canine atrial tricuspid ring in vitro.
The effect of flecainide, 0.3 mg/L and 1.0 mg/L, on inducible nonsustained reentry was studied, in vitro, in the canine tricuspid ring. Nonsustained reentry was engineered by cutting the ring and reconnecting it with an adjustable electronic delay. Delays were used that produced reentry lasting 1-3 beats (group A), 4-10 beats (group B), and 11-25 beats (group C). Reentry was initiated multiple times at each selected delay. A proarrhythmic effect, defined as a significant increase in the duration of reentry, was observed in all 14 trials at the low dose and in two of 15 trials at the high dose in seven experiments. In four more trials a transient proarrhythmic response was seen initially during exposure to the high dose. In five of seven experiments, reentry became sustained after at least one dose of flecainide. Proarrhythmic responses resulted when flecainide increased the tachycardia cycle length more than the effective refractory period and there was less cycle length oscillation after initiation. Antiarrhythmic responses resulted either from a marked increase in effective refractory period at the site of block or production of fixed block.
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Department of Medicine, University of Pennsylvania, Philadelphia.
Rhee
E K
EK
Fei
H
H
Luchetti
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W
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy; D004285:Dogs; D005424:Flecainide / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D013610:Tachycardia / Q000139:chemically induced
D005424:Flecainide