Hyperoxia and tidal volume: Independent and combined effects on neonatal pulmonary inflammation.
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.


OBJECTIVE
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 F(I)O2 = 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.
Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Mo., USA. cehlert@mail.mcw.edu
Carey A
CA
Ehlert
William E
WE
Truog
Donald W
DW
Thibeault
Uttam
U
Garg
Mike
M
Norberg
Mo
M
Rezaiekhaligh
Sherry
S
Mabry
Ikechukwu I
II
Ekekezie
D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018496:Hyperoxia / Q000378:metabolism / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects; D013552:Swine; D013990:Tidal Volume / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology
D018932:Chemokine CCL2; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase