Brief, large tidal volume ventilation initiates lung injury and a systemic response in fetal sheep

Noah Hillman, Timothy Moss, Suhas Kallapur, Cindy Bachurski, Jane Pillow, Graeme Polglase, Ilias Nitsos, Boris Kramer, Alan Jobe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

RATIONALE: Premature infants are exposed to potentially injurious ventilation in the delivery room. Assessments of lung injury are confounded by effects of subsequent ventilatory support. OBJECTIVES: To evaluate the injury response to a brief period of large tidal volume (Vt) ventilation, simulating neonatal resuscitation in preterm neonates. METHODS: Preterm lambs (129 d gestation; term is150 d) were ventilated (Vt = 15 ml/kg, no positive end-expiratory pressure) for 15 minutes to simulate delivery room resuscitation, either with the placental circulation intact (fetal resuscitation [ FR]) or after delivery (neonatal resuscitation [NR]). After the initial 15 minutes, lambs received surfactant and were maintained with either ventilatory support (FR-VS and NR-VS) or placental support (FR-PS) for 2 hours, 45 minutes. A control group received no resuscitation and was maintained with placental support. Samples of bronchoalveolar lavage fluid, lung, and liver were analyzed. MEASUREMENTS AND MAIN RESULTS: Inflammatory cells and protein in bronchoalveolar lavage fluid, heat shock protein-70 immunostaining, IL-1beta, IL-6, IL-8, monocyte chemotactic protein-1, serum amyloid A (SAA)-3, Toll-like receptor (TLR)-2, and TLR4 mRNA in the lungs were increased in the FR-PS group compared with control animals. There were further elevations in neutrophils, IL-6, and IL-8 mRNA in the FR-VS and NR-VS groups compared with FR-PS. SAA3, TLR2, and TLR4 mRNA increased in the liver in all resuscitation groups relative to control animals. CONCLUSIONS: Ventilation for 15 minutes with a Vt of 15 ml/kg initiates an injurious process in the preterm lung and a hepatic acute-phase response. Subsequent ventilatory support causes further increases in some injury indicators.
Original languageEnglish
Pages (from-to)575 - 581
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume176
Issue number6
DOIs
Publication statusPublished - 2007
Externally publishedYes

Cite this

Hillman, Noah ; Moss, Timothy ; Kallapur, Suhas ; Bachurski, Cindy ; Pillow, Jane ; Polglase, Graeme ; Nitsos, Ilias ; Kramer, Boris ; Jobe, Alan. / Brief, large tidal volume ventilation initiates lung injury and a systemic response in fetal sheep. In: American Journal of Respiratory and Critical Care Medicine. 2007 ; Vol. 176, No. 6. pp. 575 - 581.
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title = "Brief, large tidal volume ventilation initiates lung injury and a systemic response in fetal sheep",
abstract = "RATIONALE: Premature infants are exposed to potentially injurious ventilation in the delivery room. Assessments of lung injury are confounded by effects of subsequent ventilatory support. OBJECTIVES: To evaluate the injury response to a brief period of large tidal volume (Vt) ventilation, simulating neonatal resuscitation in preterm neonates. METHODS: Preterm lambs (129 d gestation; term is150 d) were ventilated (Vt = 15 ml/kg, no positive end-expiratory pressure) for 15 minutes to simulate delivery room resuscitation, either with the placental circulation intact (fetal resuscitation [ FR]) or after delivery (neonatal resuscitation [NR]). After the initial 15 minutes, lambs received surfactant and were maintained with either ventilatory support (FR-VS and NR-VS) or placental support (FR-PS) for 2 hours, 45 minutes. A control group received no resuscitation and was maintained with placental support. Samples of bronchoalveolar lavage fluid, lung, and liver were analyzed. MEASUREMENTS AND MAIN RESULTS: Inflammatory cells and protein in bronchoalveolar lavage fluid, heat shock protein-70 immunostaining, IL-1beta, IL-6, IL-8, monocyte chemotactic protein-1, serum amyloid A (SAA)-3, Toll-like receptor (TLR)-2, and TLR4 mRNA in the lungs were increased in the FR-PS group compared with control animals. There were further elevations in neutrophils, IL-6, and IL-8 mRNA in the FR-VS and NR-VS groups compared with FR-PS. SAA3, TLR2, and TLR4 mRNA increased in the liver in all resuscitation groups relative to control animals. CONCLUSIONS: Ventilation for 15 minutes with a Vt of 15 ml/kg initiates an injurious process in the preterm lung and a hepatic acute-phase response. Subsequent ventilatory support causes further increases in some injury indicators.",
author = "Noah Hillman and Timothy Moss and Suhas Kallapur and Cindy Bachurski and Jane Pillow and Graeme Polglase and Ilias Nitsos and Boris Kramer and Alan Jobe",
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Brief, large tidal volume ventilation initiates lung injury and a systemic response in fetal sheep. / Hillman, Noah; Moss, Timothy; Kallapur, Suhas; Bachurski, Cindy; Pillow, Jane; Polglase, Graeme; Nitsos, Ilias; Kramer, Boris; Jobe, Alan.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 176, No. 6, 2007, p. 575 - 581.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Brief, large tidal volume ventilation initiates lung injury and a systemic response in fetal sheep

AU - Hillman, Noah

AU - Moss, Timothy

AU - Kallapur, Suhas

AU - Bachurski, Cindy

AU - Pillow, Jane

AU - Polglase, Graeme

AU - Nitsos, Ilias

AU - Kramer, Boris

AU - Jobe, Alan

PY - 2007

Y1 - 2007

N2 - RATIONALE: Premature infants are exposed to potentially injurious ventilation in the delivery room. Assessments of lung injury are confounded by effects of subsequent ventilatory support. OBJECTIVES: To evaluate the injury response to a brief period of large tidal volume (Vt) ventilation, simulating neonatal resuscitation in preterm neonates. METHODS: Preterm lambs (129 d gestation; term is150 d) were ventilated (Vt = 15 ml/kg, no positive end-expiratory pressure) for 15 minutes to simulate delivery room resuscitation, either with the placental circulation intact (fetal resuscitation [ FR]) or after delivery (neonatal resuscitation [NR]). After the initial 15 minutes, lambs received surfactant and were maintained with either ventilatory support (FR-VS and NR-VS) or placental support (FR-PS) for 2 hours, 45 minutes. A control group received no resuscitation and was maintained with placental support. Samples of bronchoalveolar lavage fluid, lung, and liver were analyzed. MEASUREMENTS AND MAIN RESULTS: Inflammatory cells and protein in bronchoalveolar lavage fluid, heat shock protein-70 immunostaining, IL-1beta, IL-6, IL-8, monocyte chemotactic protein-1, serum amyloid A (SAA)-3, Toll-like receptor (TLR)-2, and TLR4 mRNA in the lungs were increased in the FR-PS group compared with control animals. There were further elevations in neutrophils, IL-6, and IL-8 mRNA in the FR-VS and NR-VS groups compared with FR-PS. SAA3, TLR2, and TLR4 mRNA increased in the liver in all resuscitation groups relative to control animals. CONCLUSIONS: Ventilation for 15 minutes with a Vt of 15 ml/kg initiates an injurious process in the preterm lung and a hepatic acute-phase response. Subsequent ventilatory support causes further increases in some injury indicators.

AB - RATIONALE: Premature infants are exposed to potentially injurious ventilation in the delivery room. Assessments of lung injury are confounded by effects of subsequent ventilatory support. OBJECTIVES: To evaluate the injury response to a brief period of large tidal volume (Vt) ventilation, simulating neonatal resuscitation in preterm neonates. METHODS: Preterm lambs (129 d gestation; term is150 d) were ventilated (Vt = 15 ml/kg, no positive end-expiratory pressure) for 15 minutes to simulate delivery room resuscitation, either with the placental circulation intact (fetal resuscitation [ FR]) or after delivery (neonatal resuscitation [NR]). After the initial 15 minutes, lambs received surfactant and were maintained with either ventilatory support (FR-VS and NR-VS) or placental support (FR-PS) for 2 hours, 45 minutes. A control group received no resuscitation and was maintained with placental support. Samples of bronchoalveolar lavage fluid, lung, and liver were analyzed. MEASUREMENTS AND MAIN RESULTS: Inflammatory cells and protein in bronchoalveolar lavage fluid, heat shock protein-70 immunostaining, IL-1beta, IL-6, IL-8, monocyte chemotactic protein-1, serum amyloid A (SAA)-3, Toll-like receptor (TLR)-2, and TLR4 mRNA in the lungs were increased in the FR-PS group compared with control animals. There were further elevations in neutrophils, IL-6, and IL-8 mRNA in the FR-VS and NR-VS groups compared with FR-PS. SAA3, TLR2, and TLR4 mRNA increased in the liver in all resuscitation groups relative to control animals. CONCLUSIONS: Ventilation for 15 minutes with a Vt of 15 ml/kg initiates an injurious process in the preterm lung and a hepatic acute-phase response. Subsequent ventilatory support causes further increases in some injury indicators.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994225/pdf/AJRCCM1766575.pdf

U2 - 10.1164/rccm.200701-051OC

DO - 10.1164/rccm.200701-051OC

M3 - Article

VL - 176

SP - 575

EP - 581

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

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ER -