Effect of aspiration of milk on mechanisms of neural control in the airways of developing rabbits

Abstract

We studied the effects of recurrent aspiration of milk on neural control of airways in young developing rabbits. Beginning at 1 week of age, rabbits received 0.5 ml/kg of whole milk or sterile physiologic saline intranasally while under light methoxyflourane anesthesia 5 days a week for a period of 3 weeks. At 4 and 8 weeks of age, in vitro studies of contractile and relaxant responses of tracheal smooth muscle (TSM) segments were evaluated. To assess the neurally mediated contractile responses, frequency response curves to electrical field stimulation (EFS) were performed with results expressed in terms of frequency of EFS causing 50% of the maximal contractile response (ES50) values. In addition, the contractile responsiveness of TSM to methacholine (MCh) as reflected by the concentration causing 50% of the maximal contractile response (EC50) values was also determined to evaluate the underlying cholinergic reactivity of this segment of airway. To assess nonadrenergic noncholinergic inhibitory (NANCi) responses, experiments were performed on TSM contracted with neurokinin A in the presence of atropine, propranolol, and indomethacin. EFS was delivered to the contracted tissue at stimulation frequencies ranging from 5 to 30 Hz with results expressed as mean percent relaxation. Recurrent aspiration of milk but not saline increased EFS‐induced contractile responses, as shown by significantly lower ES50 values compared with the control group: P = 0.02 and P = 0.001 at 4 and 8 weeks of age, respectively. TSM responsiveness to MCh was no different between the two groups, suggesting that alterations in prejunctional mechanisms of neural control were most likely responsible for the increased contractile response to EFS. The NANCi responses were significantly decreased by milk aspiration at both 4 and 8 weeks of age, with the abnormalities less pronounced at the later time point. These findings demonstrate that repeated aspiration of milk leads to abnormal mechanisms of neural control within airways of developing rabbits. While aspiration of milk altered both contractile and relaxant responses to EFS, the former abnormalities became more pronounced with time while the latter appeared to be resolving. These observations suggest that injury to an airway early in development does not necessarily resolve with time but may persist, with functional abnormalities becoming more pronounced even after the airway insult has ceased. Pediatr Pulmonol. 1997; 23:198–204 © 1997 Wiley‐Liss, Inc.

Bronchial hyperreactivity in non‐atopic children with asthma and reflux: Effect of anti‐reflux treatment

“…Similar findings have also been reported with aspiration and airway dysfunction. [25][26][27] Similar to the findings in this study, in some earlier studies, we have shown improvement of asthma outcomes in children with asthma and GERD, with the use of anti-GERD treatment. [8][9][10][11][12][13][14] Subsequent studies by other workers have supported our findings.…”

Aspiration: A factor in rapidly deteriorating bronchiolitis in previously healthy infants?

“…Aspiration can also have longterm effects such as food protein sensitization, abnormal neural control, increased reactivity of airways, and chronic airway dysfunction. 2,3 Additionally, aspiration could have the potential of worsening the course of bronchiolitis in an otherwise clinically stable infant with RSV bronchiolitis. We studied the possible association of aspiration with rapid clinical deterioration in previously healthy infants with RSV bronchiolitis, using the lipidladen macrophage index (LLMI) as a marker.…”

Assessing respiratory function in young children: Developmental considerations

“…32 By using this tact, it has been noted that various insults (allergen sensitization, respiratory syncytial virus infection, and aspiration) early in postnatal development can alter the normal balance of neural control within an airway toward a hyperresponsive pattern for prolonged periods of time. 25,26,33 Observations such as these have been made not only within the laboratory of authors of this review (GLL and J-KBK) but also by other investigators with an interest in the importance of the stage of development on the outcome of a pulmonary insult. For example, studies with parainfluenza type 1 virus (Sendai) showed neonatal infection of genetically susceptible rats led to chronic abnormalities in airway morphology, histology, and physiology.…”