Autonomic control of the location and rate of the cardiac pacemaker in the sinoatrial fat pad of parasympathetically denervated dog hearts

Introduction: Parasympathetic activity predominates over sympathetic activity not only with respect to heart rate but also with respect to the pacemaker location in the dog heart. After we removed the parasympathetic neural elements in the sinoatrial (SA) fat pad in the right atrium, we observed that cervical vagus stimulation did not decrease the atrial rate, but it did suppress the increase in rate evoked by sympathetic stimulation. We determined whether the pacemaker rate and location were affected by presynaptic or postsynaptic mechanisms. Methods and Results: We determined the earliest activation site by means of isochronic activation mapping of the right atrium of open chest, anesthetized dog hearts. An electrode array, which consisted of 48 unipolar electrodes, was used to record atrial activation. This array covered the three main pacemaker regions, including the SA node region. After parasympathetic nerve fibers in the SA fat pad had been denervated, vagus stimulation at 10 and 30 Hz did not decrease the heart rate, but it attenuated the increase in heart rate evoked by sympathetic stimulation or isoproterenol. Vagus stimulation at 10 Hz during sympathetic stimulation did not shift the earliest activation site from the superior pacemaker region to the SA node region in 11 of 18 experiments. However, vagus stimulation at 10 Hz during isoproterenol infusion shifted the earliest activation site to the SA node region in 11 of 13 experiments. More intense magus stimulation during combined sympathetic stimulation or isoproterenol infusion shifted the earliest activation site to the SA node or the inferior pacemaker region in 15 of 18 and in all experiments, respectively. Conclusion: The results suggest that activation of parasympathetic elements not located in the SA fat pad attenuates the increase in heart rate and the shift in pacemaker location evoked by sympathetic activation. The sympathetic and parasympathetic effects interact at presynaptic and postsynaptic sites in the dog heart.