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


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 vagus 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.


CONCLUSIONS
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.
Nakajima
Koichi
K
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Yasuyuki
Y
Kurogouchi
Fumio
F
Tsuboi
Masato
M
Chiba
Shigetoshi
S
D000273:Adipose Tissue / Q000187:drug effects / Q000294:innervation* / Q000601:surgery*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation / Q000601:surgery; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008955:Models, Cardiovascular; D010138:Pacemaker, Artificial; D017764:Parasympathectomy; D010276:Parasympatholytics / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects / Q000294:innervation* / Q000601:surgery*; D013268:Stimulation, Chemical; D014630:Vagus Nerve / Q000187:drug effects / Q000601:surgery*
D000318:Adrenergic beta-Agonists; D010276:Parasympatholytics; D001285:Atropine; D007545:Isoproterenol