Flecainide may increase the incidence of
cardiac arrhythmias in acute
ischemia. The objective of this study was to determine the cellular actions underlying this effect in an isolated tissue model of acute
ischemia and reperfusion. Transmembrane electrical activity was recorded with conventional
microelectrode techniques from epi- and endocardial surfaces of right ventricular free walls from guinea pig hearts. Endocardium was stimulated. Tissues were equilibrated in
Tyrode's solution for 60 min, then exposed to simulated
ischemia (
hypoxia,
acidosis,
lactate,
hyperkalemia, no
glucose) for 15 min and reperfused with normal
Tyrode's solution for 30 min. In the absence of
flecainide, sustained and
nonsustained ventricular tachycardia occurred in 78% of hearts during ischemic conditions and 78% in early reperfusion (n = 14).
Premature beats occurred in 14% of hearts in early reperfusion.
Ventricular tachycardia was associated with abbreviation of endocardial effective refractory period and action potential duration, plus prolongation of transmural conduction time.
Flecainide abolished
premature beats at a concentration of 1 mumol/l or higher. However, an increase in the incidence of
ventricular tachycardia occurred in both
ischemia and reperfusion at all concentrations of
flecainide (0.03-10.0 mumol/l). Proarrhythmic effects of
flecainide were associated with selective prolongation of transmural conduction time in
ischemia and early reperfusion. In epicardial slices
flecainide lengthened conduction time transverse, but not parallel to fiber orientation. Our results suggest that proarrhythmic effects of
flecainide in acute
ischemia and reperfusion are mediated by potentiation of the arrhythmogenic effects of
ischemia on anisotropic properties of the myocardium.