Effect of Timing of Vagal Stimulation on Heart Rate in the Dog

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Abstract
The effects of right vagus nerve stimulation on heart rate were examined in 16 dogs anesthetized with chloralose (60 mg/kg, iv) and urethane (600 mg/kg, iv) after a bilateral cervical vagotomy. Two protocols were followed. In the first, trains of 1, 3, or 5 stimuli, 2 msec each in duration, 10 to 15 v in magnitude, and separated by 10 msec were delivered at predetermined times after "P" wave onset as a single stimulation. In the second, the stimulation was carried out repetitively for 2 minutes at a predetermined frequency. Typically, in the first, the later in the cycle the stimulation occurred, the greater was the prolongation of the included cycle. With one stimulus in the stimulation, a typical P-P interval was 574 msec with a "P" to stimulation delay of 4 msec, and 620 msec when the "P" to stimulation delay was 200 msec. With five stimuli moving the stimulation through a range of 200 msec, the change in P-P interval was 150 msec. There was a functional dependence of the P-P cycle length on the time of arrival of the inhibitory pulse. The slope of this relationship is a function of the number of stimuli in the stimulation. With repetitive stimulation in the second protocol, there were zones wherein the heart rate synchronized to the vagal stimulation rate not only at the fundamental frequency but also at harmonics and subharmonics. This range of entrainment was also dependent upon the number of stimuli in the stimulation. The data suggest the possibility of phase shift as a mechanism for vagal regulation of heart rate.