Brief, large tidal volume ventilation initiates lung injury and a systemic response in fetal sheep.
BACKGROUND
Premature infants are exposed to potentially injurious ventilation in the delivery room. Assessments of lung injury are confounded by effects of subsequent ventilatory support.


OBJECTIVE
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.


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.
Hillman
Noah H
NH
Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Moss
Timothy J M
TJ
Kallapur
Suhas G
SG
Bachurski
Cindy
C
Pillow
J Jane
JJ
Polglase
Graeme R
GR
Nitsos
Ilias
I
Kramer
Boris W
BW
Jobe
Alan H
AH
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007378:Interleukins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008171:Lung Diseases / Q000196:embryology / Q000209:etiology* / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012121:Respiration, Artificial / Q000009:adverse effects*; D012151:Resuscitation / Q000379:methods; D000685:Serum Amyloid A Protein / Q000378:metabolism; D012720:Severity of Illness Index; D012756:Sheep; D013990:Tidal Volume; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D018932:Chemokine CCL2; D018840:HSP70 Heat-Shock Proteins; D007378:Interleukins; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4