Effects of digoxin on the chronotropic responses to repetitive vagal stimulus bursts in the dog.

We studied the effects of digoxin on the chronotropic responses of the heart to repetitive bursts of vagal stimulation in chloralose-anesthetized dogs. The frequency of the stimulus bursts was increased linearly with time. Over a certain range of frequencies, the cardiac pacemaker became synchronized with the vagal stimulation in a 1:1 ratio of heart beats to stimulus bursts. Digoxin increased the range of cardiac cycle lengths over which 1:1 synchronization occurred during repetitive vagal stimulation. This increment in the range of synchronization varied directly with the dose of digoxin. Before digoxin was given, the range of cardiac cycle lengths over which synchronization occurred when the vagus nerve was stimulated with 10 pulses per burst was 272 +/- 50 (mean +/- SE) ms. However, after a cumulative dose of 120 micrograms/kg-1 digoxin had been given, the range of 1:1 synchronization increased to 396 +/- 32 ms. Digoxin did not appear to have a proportionately greater effect on those processes that take place in the phase of the cardiac cycle during which the pacemaker cells are maximally responsive than on those processes that occur in the phase of the cycle during which the pacemaker cells are minimally responsive. Therefore, we conclude that the augmented entrainment induced by digoxin is ascribable to its tendency to enhance the chronotropic response to vagal stimulation.