The phase-dependency of the cardiac chronotropic responses to vagal stimulation as a factor in sympathetic-vagal interactions.

We determined the effects of the timing of repetitive bursts of vagal stimulation on the positive chronotropic responses of the heart to trains of cardiac sympathetic nerve stimulation in open-chest anesthetized dogs. Trains of sympathetic stimulation alone, at frequencies of 2 and 4 Hz, decreased the cardiac cycle length by 176 +/- 19 msec (mean +/- SE) and 190 +/- 22 msec, respectively. When bursts of vagal stimuli were given once each cardiac cycle and they were placed at their least effective time in the cycle, sympathetic stimulation at frequencies of 2 and 4 Hz decreased cardiac cycle length by only 107 +/- 8 and 120 +/- 8 msec, respectively. However, when the bursts of vagal stimuli were delivered at their most effective time in each cycle, the same levels of sympathetic stimulation elicited much larger reductions in cardiac cycle length (285 +/- 32 and 330 +/- 32 msec, respectively). Therefore, the effects of sympathetic stimulation were significantly attenuated by the vagal stimuli when the vagal bursts were relatively ineffective. Conversely, the chronotropic effects of the sympathetic stimulation were exaggerated substantially when the vagal stimulus bursts were initially positioned at their most effective time in the cardiac cycle. This latter response is contrary to the characteristic "accentuated antagonism," wherein the effect of any given level of sympathetic stimulation is diminished as the level of vagal activity is increased. This vagally mediated enhancement of the positive chronotropic response to sympathetic stimulation occurs because the phase dependency of the response of the automatic cells to the bursts of vagal stimulation is altered by the increased sympathetic activity.