Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias.
BACKGROUND
The goal of this study was to investigate the nature and electrophysiological mechanisms of the proarrhythmic effects of flecainide in Langendorff-perfused rabbit hearts.


RESULTS
A thin layer of epicardium was obtained by an endocardial cryotechnique in 10 Langendorff-perfused rabbit hearts. Six other hearts were kept intact. Programmed electrical stimulation using up to three closely coupled premature stimuli and burst pacing was used to test the inducibility of arrhythmias both during control and administration of 1 micrograms/ml flecainide. During control, in the thin layer of epicardium, application of one to three premature stimuli induced nonsustained ventricular tachycardia in out of 10 hearts, and burst pacing induced nonsustained ventricular tachycardia in four hearts and sustained ventricular tachycardia in two hearts. During administration of 1 microgram/ml flecainide, application of one to three premature stimuli induced sustained ventricular tachycardia in five hearts, and burst pacing induced sustained ventricular tachycardia in nine hearts. All tachycardias were based on circus movement of the impulse around arcs of functional block. During administration of flecainide, different locations of the arc of block could be found in the same heart, leading to different reentrant circuits with different cycle lengths. In the control group of six intact hearts, application of up to three closely coupled premature stimuli in all cases induced ventricular fibrillation both during control and administration of flecainide.


CONCLUSIONS
Flecainide alters propagation of the impulse in thin surviving layers of myocardium in a manner that facilitates the induction of functionally determined reentry.
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
J
J
Brugada
L
L
Boersma
C
C
Kirchhof
M
M
Allessie
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D005424:Flecainide / Q000633:toxicity*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D010477:Perfusion; D010496:Pericardium; D011817:Rabbits; D013610:Tachycardia / Q000139:chemically induced; D014693:Ventricular Fibrillation / Q000139:chemically induced
D005424:Flecainide