Frequency-dependent effects of verapamil on atrioventricular nodal conduction in man

We sought to determine if verapamil induces frequency-dependent prolongation of atrioventricular nodal conduction in 10 consecutive patients studied in the electrophysiology laboratory. We used a maintenance infusion of verapamil designed to produce plasma concentrations of verapamil in the "therapeutic" range and that did not alter heart rate or blood pressure significantly. Frequency-dependent prolongation of atrioventricular nodal conduction (AH interval) was demonstrated in all 10 patients (p less than .001), and no change in HV conduction time with decreasing cycle length was noted in any patients while receiving verapamil. Two patterns of use-dependent response were seen. In four patients frequency-dependent prolongation of the delta(AH) interval [delta(AH) = AHverapamil - AHcontrol at a given cycle length] was seen with each decrement in pacing cycle length. In six patients frequency-dependent prolongation of the delta(AH) interval was not manifest until the fifth to eighth pacing cycle length tested. There was no association between the pattern observed and the initial heart rate or AH interval. After an abrupt change in pacing cycle length, the kinetics of delta (AH) interval prolongation were rapid; equilibrium was achieved by five to eight pulses in all patients. There was no correlation between the magnitude of prolongation of the AH interval noted at a particular cycle length and the concentration of verapamil during the maintenance infusion. These results indicate that verapamil causes use-dependent prolongation of atrioventricular nodal conduction in man.