Vagal cholinergic innervation of the airways in newborn cat and dog

Abstract

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 approximately 40%, compared with approximately 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 less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of capsaicin‐ and lactic acid‐induced bronchoconstriction in the newborn dog

“…Physiological stimulation of pulmonary C fibres initiates airway reflexes aimed at limiting exposure of the airways to noxious stimuli (as reviewed in Coleridge & Coleridge, 1994;Paintal, 1973;Karlsson et al 1988); however, activation of pulmonary C fibres has also been implicated in the airway hyperreactivity accompanying inflammatory lung diseases such as asthma or, in the newborn, bronchopulmonary dysplasia (Barnes, 1986). The magnitude of the bronchoconstriction we observed to both capsaicin and lactic acid is submaximal (Fisher et al 1990) and may reflect a mechanism to enhance gas exchange by reducing dead space volume (Widdicombe, 1963) or a mechanism to protect the highly compliant airways of the newborn from dynamic compression (Bhutani et al 1986). Despite characterization of the in vivo reflex effects of capsaicin, the effects of capsaicin on pulmonary C fibres and elucidation of the molecular mechanism of action of the (RL) and dynamic lung elastance (EL,dyn) in response to right heart injections of capsaicin (arrows) in 11 newborn dogs for three separate conditions: Intact (left panels), right heart injection of capsaicin caused a brisk bronchoconstrictor response; Capsazepine (middle panels), capsaicin response blocked by capsazepine infusion; Recovery (right panels), partial recovery of the capsaicin response 15-20 min after termination of capsazepine infusion.…”

“…Tachykinins also stimulate pulmonary rapidly adapting receptors (RARs) (Matsumoto et al 1997), which can in turn evoke reflex bronchoconstriction (Coleridge et al 1989). This mechanism is precluded in our study due to the apparent absence of tachykinins in canine C fibre terminals (Russell, 1980; Fisher et al 1990). Additionally, spontaneous RAR activity in the newborn dog is very sparse, suggesting that reflex responses may also be limited (Fisher & Sant'Ambrogio, 1982).…”

“…Physiological stimulation of pulmonary C fibres initiates airway reflexes aimed at limiting exposure of the airways to noxious stimuli (as reviewed in Coleridge & Coleridge, 1994; Paintal, 1973; Karlsson et al 1988); however, activation of pulmonary C fibres has also been implicated in the airway hyper‐reactivity accompanying inflammatory lung diseases such as asthma or, in the newborn, bronchopulmonary dysplasia (Barnes, 1986). The magnitude of the bronchoconstriction we observed to both capsaicin and lactic acid is submaximal (Fisher et al 1990) and may reflect a mechanism to enhance gas exchange by reducing dead space volume (Widdicombe, 1963) or a mechanism to protect the highly compliant airways of the newborn from dynamic compression (Bhutani et al 1986).…”

Inflammatory mechanisms linking maternal and childhood asthma

“…Fetal programming can have long‐term consequences on airway function. Airway hyperreactivity can be detected at birth in newborn animals and neonatal airway hyperreactivity in humans is associated with increased risk of asthma in adolescence Maternal atopy and asthma are associated with impaired infant lung function and airway hyperreactivity, independent of allergen sensitization at birth. Postnatal allergen sensitization further augments airway hyperreactivity in children exposed to maternal asthma and allergen sensitization predicts the persistence of wheeze …”

Inflammation and Autonomic Function

“…The parasympathetic nervous system (PSNS) innervates multiple organ systems, including cardiovascular, respiratory, immune, and endocrine systems [43] and plays a critical role in a diverse array of physiological processes, such as inflammation, immune response, heart rate, gastrointestinal peristalsis, and digestion [13]. About 75% of parasympathetic innervation comes from the tenth cranial nerve, the vagus nerve (VN), that extends throughout the body, and is the largest nerve and main parasympathetic division of the autonomic nervous system [13,30,44]. Vagus nerve comprises both sensory afferent neurons, crucial for conducting peripheral immune signals to the brain, which integrate the visceral sensory information and coordinates the autonomic function and visceral activity [13,33,34], and motor efferent neurons, which integrate the information that was delivered to the central nervous system and control the peripheral effectors [30,45].…”