L-NAME (NG-nitroarginine methyl ester) establishes foetal growth restriction and induces structural and functional lung changes in a multi-insult animal model of bronchopulmonary dysplasia

<bold>Introduction:</bold> Despite advances in the care of preterm-born infants, foetal growth restriction (FGR) and bronchopulmonary dysplasia (BPD) remain a significant cause of morbidity and mortality. With the pathophysiology of BPD being complex, FGR is a recognised risk factor for developing BPD. Current animal models of BPD utilise a single postnatal insult of exposure to severe hyperoxia (FiO2>95%) in contrast to clinical practice guidelines in neonatology. This single insult effectively induces histological changes of classic BPD. We hypothesized that combining FGR with milder postnatal hyperoxia (FiO2:70%) would create a more clinically relevant BPD model. <bold>Methods:</bold> Pregnant NZW rabbits were injected with L-NAME (62.5mg/kg) or saline on gestational day (GD)24-27 and kits delivered preterm on GD28 (term:GD31). Kits were randomised to hyperoxia or normoxia. Lung function testing was performed at 3 time points and lungs harvested for analysis. <bold>Results:</bold> L-NAME kits were significantly smaller at birth and postnatal day 7 (PND7). On PND1, airway and alveolar resistance were increased and lung compliance decreased in L-NAME kits. On PND7, multiple insults led to smaller, less compliant lungs with increased elastance. All experimental groups had increased mean linear intercepts on histological analysis, and increased mean transectional wall length in the multi-insult group. <bold>Conclusion:</bold> L-NAME effectively established FGR. FGR alone had a detrimental effect on structural and functional lung development. BPD-like changes in lung function and structure were induced by combining pre- and postnatal insults.