Heart rate-independent vagal effect on end-systolic elastance of the canine left ventricle under various levels of sympathetic tone.

BACKGROUND Although we have shown that in rabbits the direct (heart rate [HR]-independent) vagal effect on left ventricular end-systolic elastance (E(es)) was negligible under minimal sympathetic tone, how underlying sympathetic tone modulates the inotropic response to vagal stimulation remains unknown. METHODS AND RESULTS We used an isolated canine heart preparation with functioning autonomic nerves. We examined the direct vagal inotropic effect by measuring E(es) under fixed-rate atrial pacing with or without concomitant sympathetic nerve stimulation. Right and left vagal stimulation at 20 Hz decreased HR by 27+/-3% and 14+/-2%, respectively, and decreased E(es) by 11+/-2% and 6+/-2%, respectively. When we fixed HR by atrial pacing, right and left vagal stimulation at 20 Hz did not decrease E(es) (0.01+/-0.3% and 0.3+/-0.4%; NS). Concomitant left sympathetic nerve stimulation at 4 Hz enhanced direct vagal negative inotropism to -19+/-3% and -34+/-5% for 20-Hz right and left vagal stimulation (interaction, P<0.01). CONCLUSIONS Direct vagal negative inotropism was unobservable with minimal sympathetic tone in dogs but was enhanced with concomitant sympathetic stimulation.