MODULATION OF PROCAINAMIDES EFFECT ON CONDUCTION BY CELLULAR UNCOUPLING IN PERFUSED RABBIT HEARTS

Introduction: How cell-to-cell electrical coupling influences an antia rrhythmic agent's effect on conduction is largely unknown. To investig ate this, we evaluated the effects of procainamide on myocardial condu ction at decreasing degrees of cell-to-cell electrical coupling induce d by graded doses of heptanol. Methods and Results: Electrograms were recorded from 50 ventricular epicardial sites in a 1 cm x 0.5 cm area during pacing to produce conduction longitudinal or transverse to myoc ardial fiber orientation in Langendorff-perfused rabbit hearts. The ef fects of procainamide (15 mg/L) on conduction velocity were determined in the presence of increasing doses of heptanol (0.2, 0.5, and 1.0 mM ). In addition, using standard microelectrode techniques in isolated s uperfused rabbit myocardium, intracellular potentials were recorded in the presence df 15 mg/L procainamide and heptanol (1.0 mM). In the ab sence of heptanol, procainamide slowed conduction velocity. In the pre sence of increasing doses of heptanol, procainamide's contribution to the depressant effect on conduction velocity was attenuated and revers ed at the highest dose. The latter effect was preferentially seen for conduction longitudinal to myocardial fiber orientation, Heptanol had no effect on action potential amplitude or maximum rate of depolarizat ion in the presence of procainamide. Conclusions: Procainamide's effec t on conduction velocity is influenced by the underlying degree of cel l-to-cell electrical coupling. The present model should be useful in e valuating the relative ability of other pharmacologic agents to modula te conduction under conditions of changing cell coupling.