Time-dependent changes in the chronotropic response to vagal stimulation in the newborn canine

We characterized changes in the vagal chronotropic response during 3-min trains of vagal stimulation at 3, 5, and 8 Hz in anesthetized, chemically sympathectomized (6-hydroxydopamine) newborn canines (< 15 d of age). In response to vagal stimulation, the sinus cycle length gradually 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 adult dogs, the degree of attenuation of the vagal chronotropic response (fade) was also highly dependent upon the frequency of vagal stimulation in the range 3-8 Hz (p < 0.002). We then compared the maximum change in sinus cycle length and fade in a group of neonates while stimulating the vagus at 3 Hz before and after the administration of physostigmine (0.2 mg/kg i.v.). Physostigmine resulted in a significant increase not only in the maximum percent change in sinus cycle length but in the magnitude of attenuation of the vagal response as well. Therefore, unlike the adult, in the newborn the magnitude of both the vagal response and fade are dependent upon concentrations of acetylcholine released in response to modest levels of vagal stimulation (< or = 8 Hz). This may be the result of differences between the newborn and the adult in the prestreceptor mechanisms of fade or in the susceptibility of the muscarinic receptor to desensitization by the neurotransmitter acetylcholine.