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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.

SUBMITTER: Hillman NH 

PROVIDER: S-EPMC1994225 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Hillman Noah H NH   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  

American journal of respiratory and critical care medicine 20070719 6


<h4>Rationale</h4>Premature infants are exposed to potentially injurious ventilation in the delivery room. Assessments of lung injury are confounded by effects of subsequent ventilatory support.<h4>Objectives</h4>To evaluate the injury response to a brief period of large tidal volume (Vt) ventilation, simulating neonatal resuscitation in preterm neonates.<h4>Methods</h4>Preterm lambs (129 d gestation; term is150 d) were ventilated (Vt = 15 ml/kg, no positive end-expiratory pressure) for 15 minut  ...[more]

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