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Delineating the differential effects of oxygen and ventilation on structural changes during lung injury in very immature ovine fetal lungs

Presented at the Neonatal Society 2010 Autumn Meeting.

Allison BJ, Flecknoe SJ, Williams C, Crossley KJ, Davis PJ, Morley CJ, Hooper SB

Monash Institute of Medical Research, Ritchie Centre, Melbourne

Background: It has previously been difficult to delineate the separate roles of oxygen and ventilation on preterm lung injury. We have used an animal model of in utero ventilation to investigate the separate effects of ventilation and acute oxygen exposure on the very immature lung.

Methods: Fetal sheep were ventilated (PIP 35cmH2O, PEEP 6cmH2O) in utero at 110d gestation for 6h with either 100%, 21% or 0% (100% nitrogen) oxygen (n=5 each) and survived in utero, without further ventilation, until tissue collection at 118d. Non-ventilated 110d and 118d fetuses were controls.

Results: All IUV exposed fetuses had reduced secondary septal crest densities (21% O27.4±0.6%, 100% O2 7.3±1.1% and 100% N2 6.5±1.1% vs 118d control 11.1±0.6% (p<0.01)) and increased elastin (100% O2, 4.7±0.6%; 21% O2, 3.7±0.7% and 100% N2 2.9±0.6% vs 118d control 1.3±0.9%) staining irrespective of FiO2. IUV with 100% and 21% oxygen (47.2±5.1% and 45.4±3.3% respectively), but not 100% nitrogen (35.8±5.6%), increased lung tissue volumes compared to control (32.5±2.4%; p<0.05). Myofibroblast differentiation and apoptosis were also affected significantly in a dose dependent manner.

Conclusion: This study shows that IUV without oxygen can reduce alveolarization, whereas ventilation with oxygen, even with only air (21%), increases lung tissue volumes, elastin deposition, myofibroblast differentiation and apoptosis.

Corresponding author: bja29@cam.ac.uk

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