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Vol. 90, No. 2, 2006
Issue release date: August 2006
Biol Neonate 2006;90:89–97

Hyperoxia and Tidal Volume: Independent and Combined Effects on Neonatal Pulmonary Inflammation

Ehlert C.A. · Truog W.E. · Thibeault D.W. · Garg U. · Norberg M. · Rezaiekhaligh M. · Mabry S. · Ekekezie I.I.
aSection of Neonatal-Perinatal Medicine, bSection of Pathology, Department of Pediatrics, Children’s Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Mo., USA

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Background: Hyperoxia and tidal volume mechanical ventilation are independent factors in the genesis of lung injury, but it remains unclear the extent to which each is responsible or contributes to this process in newborns. Objectives: To study the independent and combined effects of hyperoxia and tidal volume mechanical ventilation on the induction of lung inflammation in a newborn piglet model of ventilator-induced lung injury. Methods: Following exposure to either ambient air or FIO2 = 1.0 for a period of 3 days, newborn piglets were randomized to receive mechanical ventilation with either high tidal volume (20 ml/kg) or low tidal volume (6 ml/kg) for 4 h while controlling for pH. Results: Monocyte chemoattractant protein-1 level in the lungs of animals randomized to hyperoxia with high tidal volume ventilation was significantly elevated, compared to all other groups (p < 0.05). Myeloperoxidase assayed in lung homogenate was found to be significantly higher in nonventilated animals exposed to hyperoxia (p < 0.01). Only in animals previously exposed to hyperoxia did the addition of high tidal volume ventilation further increase the level of myeloperoxidase present (p < 0.05). Pulmonary vascular resistance was significantly elevated after 4 h of mechanical ventilation compared to 1 h (p < 0.001). Conclusions: We conclude that in neonatal piglets undergoing hyperoxic stress, superimposition of high tidal volume ventilation exacerbates the lung inflammation as assessed by lung monocyte chemoattractant protein-1 and level of myeloperoxidase.

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