Abstract
Maternal infection is a risk for preterm delivery. Preterm newborns often require supplemental oxygen to treat neonatal respiratory distress. Newborn hyperoxia exposure is associated with airway and vascular hyperreactivity, while the complications of maternal infection are variable. In a mouse model of prenatal maternal intraperitoneal lipopolysaccharide (LPS, embryonic day 18) with subsequent newborn hyperoxia (40% oxygen × 7 days) precision-cut living lung slices were used to measure intrapulmonary airway and vascular reactivity at 21 days of age. Hyperoxia increased airway reactivity to methacholine compared to room air controls. Prenatal maternal LPS did not alter airway reactivity in room air. Combined maternal LPS and hyperoxia exposures increased airway reactivity vs. controls, although maximal responses were diminished compared to hyperoxia alone. Vessel reactivity to serotonin did not significantly differ in hyperoxia or room air; however, prenatal maternal LPS appeared to attenuate vessel reactivity in room air. Following room air recovery, LPS with hyperoxia lungs displayed upregulated inflammatory and fibrosis genes compared to room air saline controls (TNFαR1, iNOS, and TGFβ). In this model, mild newborn hyperoxia increases airway but not vessel reactivity. Prenatal maternal LPS did not further increase hyperoxic airway reactivity. However, inflammatory genes remain upregulated weeks after recovery from maternal LPS and newborn hyperoxia exposures.
Highlights
Introduction published maps and institutional affilTreatment with supplemental oxygen for neonatal respiratory distress is common following preterm birth [1]
Airways from hyperoxia-exposed mouse pups pretreated with maternal saline (N = 9 pups) were more reactive than normoxia salinetreated mice (N = 9) as indicated by the notable decrease in lumen area in response to increasing doses of methacholine
Airway reactivity to methacholine in normoxia-exposed mice was similar between mice that were from either maternal saline or LPS (N = 8) litters, suggesting that maternal LPS alone did not impact airway reactivity compared to saline control mice
Summary
Introduction published maps and institutional affilTreatment with supplemental oxygen for neonatal respiratory distress is common following preterm birth [1]. While the mechanisms underlying airway hyperreactivity are multi-factorial [5], there is increasing awareness that modest exposures of the preterm lung to just several days of supplemental oxygen may contribute to short- and longer-term respiratory pathophysiology, even in infants without chronic lung disease [6,7,8]. Newborn rodent models show that exposure to mild and moderate neonatal hyperoxia (40–60% inspired O2 ) when compared to severe hyperoxia (>70% inspired O2 ) results in long-term increases in airway hyperreactivity [9,10,11]. Hyperoxia exposure is associated with pulmonary arterial hypertension in the preterm neonate [12,13]; and the effects of newborn hyperoxia in rodent models show variably increased pulmonary vessel hyperreactivity [14,15,16,17]. Hyperoxia exposure is associated with pulmonary arterial hypertension in the preterm neonate [12,13]; and the effects of newborn hyperoxia in rodent models show variably increased pulmonary vessel hyperreactivity [14,15,16,17]. iations.
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