Published ahead of print on July 19, 2007, doi:10.1164/rccm.200701-051OC Am. J. Respir. Crit. Care Med., Volume 176, Number 6, September 2007, 575-581 A more recent version of this article appeared on September 15, 2007
Submitted on January 10, 2007 Brief, Large Tidal Volume Ventilation Initiates Lung Injury and a Systemic Response in Fetal SheepNoah H Hillman1,1 Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 2 School of Women's and Infants' Health, The University of Western Australia, Perth, Australia, 3 Department of Pediatrics/Neonatology, Academisch Ziekenhuis Maastricht, Maastricht, The Netherlands * To whom correspondence should be addressed. E-mail: alan.jobe{at}cchmc.org.
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.
Objective: To evaluate the injury response to a brief period of large tidal volume ventilation, simulating neonatal resuscitation in preterm neonates.
Design/Methods: Preterm lambs (129d gestation; term is 150d) were ventilated (VT=15 mL/kg, no PEEP) for 15min to simulate delivery room resuscitation, either with the placental circulation intact (fetal resuscitation, FR-) or after delivery (neonatal resuscitation, NR-). After the initial 15min, lambs received surfactant and were maintained with either ventilatory support (FR-VS and NR-VS) or placental support (FRPS) for 2h 45min. A control group received no resuscitation and were maintained with placental support. Samples of bronchoalveolar lavage fluid (BALF), lung and liver were analyzed. Results: Inflammatory cells and protein in BALF, HSP-70 immunostaining, IL-1 Key words: Resuscitation, premature, bronchopulmonary dysplasia, positive end expiratory pressure, volutrauma
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, IL-6, IL-8, MCP-1, SAA3, TLR2 and TLR4 mRNA in the lungs were increased in the FR-PS group compared to controls. 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 controls.
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.
