Preterm infants in the NICU often require supplemental O2 (ie. Hyperoxia) to ensure healthy oxygen intake. One consequence of supplemental O2 therapy can manifest as airway (AW) hyperreactivity, which is an underlying feature of lung disease (ie. bronchopulmonary dysplasia) and various wheezing disorders. The neonatal mouse exposed to hyperoxia in the early postnatal period is a common animal model used to induce airway hyperreactivity and replicate a preterm infant with BPD. The purpose of this study was to develop a rat model of airway hyperreactivity. Neonatal rats received hyperoxia (40% inspired O2) 24 hours/day for their first five postnatal days (p1-p5). On the sixth day (p6), the rats were sacrificed and AW reactivity to increasing doses of methacholine (0.25μM-8μM) were measured. It was found that 40% O2 increased airway reactivity compared to age-matched rats raised in normoxia. Hyaluronan has previously shown to play a role in AW hyperreactivity seen in other lung disease models. The slices were then tested to determine whether airway hyperreactivity following neonatal hyperoxia is associated with increased hyaluronan signaling. Whole lung mRNA expression revealed increased HAS1 (lung hyaluronan synthase 1) mRNA expression following hyperoxia, which implies increased synthesis of high molecular weight hyaluronan. This suggests hyaluronan may play a role in airway reactivity commonly seen in preterm infants with BPD. Additionally, neonatal rats may also be a viable model of airway reactivity associated with BPD.
