We have previously shown that exposure of rat pups to >95% O2 during alveolarization (postnatal d4-14) causes an increase in LT production along with severe inhibition of alveolarization measured on d14. Preventing the formation of LTs using the FLAP inhibitor, MK-0591, during O2 exposure (d4-14) allows alveolar development to occur normally. We wanted to investigate whether or not there was a critical period during alveolarization for the O2 effect on the developing lung and if so, whether this could be connected with a critical period for LT effects.

Project (1): Rat pups were placed in >95% or 21% O2 from d4-9, 9-14, or 4-14. Morphometric analysis was performed on d14 and lung LT production was measured on d9 and 14. Pups exposed to hyperoxia from d4-9 and 4-14 had significantly larger airspace unit volume (p<0.01) compared to air controls and all other hyperoxic groups. They also had a significantly lower alveolar perimeter to area ratio (p<0.05). The% of parenchymal tissue was significantly lower than the air control group (p<0.05) for all hyperoxic groups (p<0.05). LT levels were significantly higher at d9 in animals exposed to O2 from d4-9 than the control group (p<0.01) compared to air exposed animals. These levels were back to normal by d14. Animals exposed to O2 from d9-14 and 4-14 had elevated LTs at d14 (p<0.05) compared to air controls of the same age.

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