TIME-DEPENDENT CHANGES IN THE CHRONOTROPIC RESPONSE TO VAGAL-STIMULATION IN THE NEWBORN CANINE

We characterized changes in the vagal chronotropic response during 3-m in trains of vagal stimulation at 3, 5, and 8 Hz in anesthetized, chem ically sympathectomized (6-hydroxydopamine) newborn canines (<15 d of age). In response to vagal stimulation, the sinus cycle length gradual ly increased (within 30 s) to a maximum value that was dependent upon the stimulation frequency (p < 0.001). The chronotropic response then attenuated over the remainder of the vagal train. However, unlike in a dult dogs, the degree of attenuation of the vagal chronotropic respons e (fade) was also highly dependent upon the frequency of vagal stimula tion in the range 3-8 Hz (p < 0.002). We then compared the maximum cha nge in sinus cycle length and fade in a group of neonates while stimul ating the vagus at 3 Hz before and after the administration of physost igmine (0.2 mg/kg i.v.). Physostigmine resulted in a significant incre ase not only in the maximum percent change in sinus cycle length but i n the magnitude of attenuation of the vagal response as well. Therefor e, unlike the adult, in the newborn the magnitude of both the vagal re sponse and fade are dependent upon concentrations of acetylcholine rel eased in response to modest levels of vagal stimulation (less-than-or- equal-to 8 Hz). This may be the result of differences between the newb orn and the adult in the prestreceptor mechanisms of fade or in the su sceptibility of the muscarinic receptor to desensitization by the neur o-transmitter acetylcholine.