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

Andrew S. Gelfand, Gary L. Larsen, Joan E. Loader, Juanita P. Graves, Leland L. Fan, Giuseppe N. Colasurdo

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)198-204
Number of pages7
JournalPediatric Pulmonology
Volume23
Issue number3
DOIs
StatePublished - Mar 1997

Fingerprint

Airway Management
Electric Stimulation
Milk
Rabbits
Smooth Muscle
Methacholine Chloride
Neurokinin A
Atropine
Propranolol
Indomethacin
Cholinergic Agents
Anesthesia
Light
Control Groups
Wounds and Injuries

Keywords

  • airway development
  • airways
  • aspiration
  • milk
  • neural control
  • nonadrenergic noncholinergic inhibition

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Effect of aspiration of milk on mechanisms of neural control in the airways of developing rabbits. / Gelfand, Andrew S.; Larsen, Gary L.; Loader, Joan E.; Graves, Juanita P.; Fan, Leland L.; Colasurdo, Giuseppe N.

In: Pediatric Pulmonology, Vol. 23, No. 3, 03.1997, p. 198-204.

Research output: Contribution to journalArticle

Gelfand, Andrew S. ; Larsen, Gary L. ; Loader, Joan E. ; Graves, Juanita P. ; Fan, Leland L. ; Colasurdo, Giuseppe N. / Effect of aspiration of milk on mechanisms of neural control in the airways of developing rabbits. In: Pediatric Pulmonology. 1997 ; Vol. 23, No. 3. pp. 198-204.
@article{48cf8551d4a9455787af3c8b26ef4558,
title = "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.",
keywords = "airway development, airways, aspiration, milk, neural control, nonadrenergic noncholinergic inhibition",
author = "Gelfand, {Andrew S.} and Larsen, {Gary L.} and Loader, {Joan E.} and Graves, {Juanita P.} and Fan, {Leland L.} and Colasurdo, {Giuseppe N.}",
year = "1997",
month = "3",
doi = "10.1002/(SICI)1099-0496(199703)23:3<198::AID-PPUL5>3.0.CO;2-K",
language = "English (US)",
volume = "23",
pages = "198--204",
journal = "Pediatric Pulmonology",
issn = "8755-6863",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Effect of aspiration of milk on mechanisms of neural control in the airways of developing rabbits

AU - Gelfand, Andrew S.

AU - Larsen, Gary L.

AU - Loader, Joan E.

AU - Graves, Juanita P.

AU - Fan, Leland L.

AU - Colasurdo, Giuseppe N.

PY - 1997/3

Y1 - 1997/3

N2 - 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.

AB - 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.

KW - airway development

KW - airways

KW - aspiration

KW - milk

KW - neural control

KW - nonadrenergic noncholinergic inhibition

UR - http://www.scopus.com/inward/record.url?scp=0030940128&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030940128&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1099-0496(199703)23:3<198::AID-PPUL5>3.0.CO;2-K

DO - 10.1002/(SICI)1099-0496(199703)23:3<198::AID-PPUL5>3.0.CO;2-K

M3 - Article

VL - 23

SP - 198

EP - 204

JO - Pediatric Pulmonology

JF - Pediatric Pulmonology

SN - 8755-6863

IS - 3

ER -