Respiratory Function in a Novel Neonatal Rat Model of Early Life Oxygen Dysregulation and Subsequent Immune Challenge

Preterm infant immaturity is characterised by unstable cardiorespiratory control, with male infants exhibiting poorer clinical outcomes. Very/Extremely preterm infants are at an increased risk of infection in early life. Infections are often caused by Gram‐positive bacteria that activate inflammatory pathways. We sought to characterise respiratory function and redox status in response to early life oxygen dysregulation (intermitted hypoxia and hyperoxia) and subsequent immune challenge using gram positive bacterial proteins. This study was approved by local animal ethics committee and the national regulatory body, HPRA Ireland. On postnatal day (PND) three, Sprague Dawley litters were exposed for 10 days to either cIHH or sham conditions. Following intraperitoneal ( i.p ) administration of LTA+PGN or vehicle solution on PND13, animals were monitored for 3 hours using whole body plethysmography. VCO 2 was measured in parallel. A separate cohort of animals were exposed to an autoresuscitation protocol which consisted of acute anoxia until primary gasp and subsequent recovery in normoxic conditions (FiO 2 21%). In littermates exposed to either cIHH/Sham and subsequent LTA+PGN/vehicle administration, blood, plasma and tissue was collected post‐mortem. Blood (pH and lactate) analysis was performed, plasma cortisol concentrations were quantified, and mRNA expression of NAD(P)H Quinone Dehydrogenase 1 was quantified in the diaphragm muscle. All data were analysed using a three‐way ANOVA (factors: sex, gas, drug), n=8‐10. There was a small decrease in the ventilatory equivalent following cIHH exposure (gas P