Electrophysiological-anatomic correlates of adenosine 5 triphosphate-triggered vagal reflex in the dog. iii: role of cardiac afferents. Katchanov, Guennadi, Jiang Xu, Carl M. Hurt, and Amir Pelleg. Likoff Cardiovascular Institute, Department of Medicine, Medical College of Pennsylvania and Hahnemann University, Philadelphia, PA
APStracts 2:0482H, 1995.
To test the hypothesis that the asymmetry in the afferent traffic of the intra-right atrium (RA) ATP-triggered vagal reflex is due to the stimulation by ATP of extra-pulmonary, i.e., cardiac, vagal chemosensitive afferent terminals, ATP and adenosine (1-6 [mu]mol/kg) and capsaicin (0.016-0.098 [mu]mol/kg) were given into the canine RA and the aortic root (AR) (n=12); ATP and adenosine were also administered into the left common carotid artery and the descending aorta (n=6). The negative chronotropic action of the test compounds was quantitated as the largest percent prolongation of sinus cycle length (%_SCL). In addition, time to peak effect (tp) was determined for each administration of the test compounds, as seconds elapsed from the time of administration to the appearance of the longest SCL. Under baseline conditions, ATP given into the left common carotid artery had a relatively very small effect (%_ SCL of 49+/-18); ATP given into the descending aorta had no effect. In contrast, intra-RA and intra-AR ATP markedly suppressed sinus node automaticity; the former less than the latter (%_SCL of 302+/-56 vs. 379+/-76, respectively; p&LT0.05); the opposite was true for capsaicin (%_SCL of 133+/-21 vs. 64+/-34, respectively; p&LT0.05). At equimolar doses, intra-RA adenosine was much less potent than intra -RA ATP (%_SCL of 63+/-13 vs. 302+/-56, p&LT0.05). Pulmonary denervation did not alter the effects of either intra-RA ATP, intra -AR ATP or intra-AR capsaicin but almost abolished the effect of intra-RA capsaicin. Subsequent left cervical vagotomy did not alter the effects of ATP (given at the two sites), however, under conditions of bilateral vagotomy, the effects of ATP were markedly reduced. Under these conditions, there was no difference between the effects of ATP and that of adenosine. In addition, under baseline conditions, tp of intra-RA ATP was larger than that of intra-AR ATP (12.1+/-1.3 sec vs. 5.4+/-0.6 sec, p&LT0.05). The latter was also much smaller than that of intra-RA adenosine, (i.e., 16.2+/-0.9 sec). Under conditions of pulmonary denervation plus bilateral cervical vagotomy, tp of intra-RA and intra-AR ATP increased substantially and was similar to tp of adenosine. It was concluded that (i) ATP can stimulate vagal afferent terminals not only in the lungs but also in the heart, (ii) the latter constitutes the vagal component of the negative chronotropic action of either intra RA- or intra-AR ATP on sinus node automaticity, and (iii) the asymmetry in the vagal afferent traffic elicited by ATP in the heart (i.e., right vagal dominance) supersedes the symmetric vagal afferent traffic triggered by intra-pulmonary ATP. This explains the right vagal dominance in the vagal afferent traffic elicited by intra-RA ATP. Since ATP is released in the heart during acute myocardial ischemia, it can be hypothesized that ATP- triggered cardio-cardiac reflex could play a role in bradyarrhythmias associated with these pathophysiologic conditions. 

Received 31 May 1995; accepted in final form 11 October 1995.
APS Manuscript Number H503-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95