VAGAL CHOLINERGIC INNERVATION OF THE AIRWAYS IN NEWBORN CAT AND DOG

Although several studies have examined the pulmonary response to muscarinic agonists in the newborn, none has addressed the functional capabilities or 'maturity' of vagal innervation to airway smooth muscle in the newborn. The purpose of the present study was to provide a quantitative analysis of the ability of vagal excitatory innervation (encompassing the pre- and postganglionic fibers, airway ganglia, and airway smooth muscle) to alter pulmonary mechanics in the newborn. We measured the changes in pulmonary mechanics elicited by electrical stimulation of the vagus nerves in 20 newborn cats and 18 puppies anesthetized with chloralose urethan. Animals were tracheotomized and ventilated (chest open), and the cervical vagus nerves were sectioned and placed on stimulating electrodes. Animals were placed in a flow plethysmograph, and mean inspiratory resistance (RL,I) and dynamic compliance were measured on a breath-by-breath basis. In each animal RL,I increased, dynamic compliance decreased, and heart rate slowed during 10 s of vagal stimulation at frequencies ranging from 2 to 20 pulses/s. At each stimulus frequency there was a spectrum of responses with respect to the percent change in RL,I. At 15 pulses/s there was a fourfold difference in the RL,I response of the most- and least-sensitive animals. In both species, higher stimulus frequencies caused greater increases in RL,I; at 2 pulses/s RL,I increased on average ~40%, compared with ~250% at 20 pulses/s. The increase in RL,I was similar in the kitten and puppy at stimulus frequencies of 6 and 15 pulses/s but was less in the kitten at 2 pulses/s (P < 0.01). Bradycardia induced by stimulation at 6 and 15 pulses/s was significantly greater in the newborn dog than in the cat. We conclude that vagal cholinergic innervation to the airways is functional at birth and that the responses elicited were due entirely to activation of muscarinic receptors because atropine eliminated any cardiopulmonary effects. We speculate that the characteristics determining an individual's airway responsiveness are present at birth and are demonstrable physiologically.