Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

Beth J. Allison, Stuart B. Hooper, Elise Coia, Valerie A. Zahra, Graham Jenkin, Atul Malhotra, Arvind Sehgal, Martin Kluckow, Andrew W. Gill, Foula Sozo, Suzanne L. Miller, Graeme R. Polglase

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Intrauterine growth restriction (IUGR) and preterm birth are frequent co-morbidities and, combined, increase the risk of adverse respiratory outcomes compared to that in appropriately grown infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared to appropriately grown infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements and/or increased ventilation induced lung injury Methods: IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 hours before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. RESULTS: IUGR preterm lambs weighed 30 less than appropriately grown (AG) preterm lambs, with increased brain:body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared to AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth, and had significant, but similar, increases in pro-inflammatory cytokine expression, lung injury markers gene expression and surfactant phosphatidylcholine species compared to unventilated controls. CONCLUSION: IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.
Original languageEnglish
Pages (from-to)L213 - L223
Number of pages11
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume310
Issue number3
DOIs
Publication statusPublished - 2016

Cite this

@article{d4e8c68cf2b747189e9e2fd2f049240b,
title = "Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs",
abstract = "Intrauterine growth restriction (IUGR) and preterm birth are frequent co-morbidities and, combined, increase the risk of adverse respiratory outcomes compared to that in appropriately grown infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared to appropriately grown infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements and/or increased ventilation induced lung injury Methods: IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 hours before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. RESULTS: IUGR preterm lambs weighed 30 less than appropriately grown (AG) preterm lambs, with increased brain:body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared to AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth, and had significant, but similar, increases in pro-inflammatory cytokine expression, lung injury markers gene expression and surfactant phosphatidylcholine species compared to unventilated controls. CONCLUSION: IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.",
author = "Allison, {Beth J.} and Hooper, {Stuart B.} and Elise Coia and Zahra, {Valerie A.} and Graham Jenkin and Atul Malhotra and Arvind Sehgal and Martin Kluckow and Gill, {Andrew W.} and Foula Sozo and Miller, {Suzanne L.} and Polglase, {Graeme R.}",
year = "2016",
doi = "10.1152/ajplung.00328.2015",
language = "English",
volume = "310",
pages = "L213 -- L223",
journal = "American Journal of Physiology - Lung Cellular and Molecular Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "3",

}

Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs. / Allison, Beth J.; Hooper, Stuart B.; Coia, Elise; Zahra, Valerie A.; Jenkin, Graham; Malhotra, Atul; Sehgal, Arvind; Kluckow, Martin; Gill, Andrew W.; Sozo, Foula; Miller, Suzanne L.; Polglase, Graeme R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 310, No. 3, 2016, p. L213 - L223.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

AU - Allison, Beth J.

AU - Hooper, Stuart B.

AU - Coia, Elise

AU - Zahra, Valerie A.

AU - Jenkin, Graham

AU - Malhotra, Atul

AU - Sehgal, Arvind

AU - Kluckow, Martin

AU - Gill, Andrew W.

AU - Sozo, Foula

AU - Miller, Suzanne L.

AU - Polglase, Graeme R.

PY - 2016

Y1 - 2016

N2 - Intrauterine growth restriction (IUGR) and preterm birth are frequent co-morbidities and, combined, increase the risk of adverse respiratory outcomes compared to that in appropriately grown infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared to appropriately grown infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements and/or increased ventilation induced lung injury Methods: IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 hours before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. RESULTS: IUGR preterm lambs weighed 30 less than appropriately grown (AG) preterm lambs, with increased brain:body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared to AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth, and had significant, but similar, increases in pro-inflammatory cytokine expression, lung injury markers gene expression and surfactant phosphatidylcholine species compared to unventilated controls. CONCLUSION: IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.

AB - Intrauterine growth restriction (IUGR) and preterm birth are frequent co-morbidities and, combined, increase the risk of adverse respiratory outcomes compared to that in appropriately grown infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared to appropriately grown infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements and/or increased ventilation induced lung injury Methods: IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 hours before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. RESULTS: IUGR preterm lambs weighed 30 less than appropriately grown (AG) preterm lambs, with increased brain:body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared to AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth, and had significant, but similar, increases in pro-inflammatory cytokine expression, lung injury markers gene expression and surfactant phosphatidylcholine species compared to unventilated controls. CONCLUSION: IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.

UR - http://ajplung.physiology.org/content/ajplung/310/3/L213.full.pdf

U2 - 10.1152/ajplung.00328.2015

DO - 10.1152/ajplung.00328.2015

M3 - Article

VL - 310

SP - L213 - L223

JO - American Journal of Physiology - Lung Cellular and Molecular Physiology

JF - American Journal of Physiology - Lung Cellular and Molecular Physiology

SN - 1040-0605

IS - 3

ER -