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Dynamic lipidomic mass spectrometry of endotracheal secretions and plasma from preterm infants mechanically ventilated on the neonatal intensive care unit

Presented at the Neonatal Society 2012 Summer Meeting (programme).

Goss KCW1,2,3, Goss VM1,2, Townsend JP1, Gunda R3, Koster G2, Hall M3, Thwaites R4, Clark HW1,2,3, Postle AD1,2

1 Southampton Centre for Biomedical Research, NIHR Respiratory Biomedical Research Unit, Southampton, UK
2 Division of Clinical Experimental Science, Faculty of Medicine, University of Southampton, , Southampton, UK
3 Princess Anne Hospital, Southampton, UK
4 Queen Alexandra Hospital, Portsmouth, UK

Background: While the introduction of exogenous surfactant therapy has dramatically improved the survival of premature infants delivered between 24 and 28 weeks gestation, the turnover and synthesis of surfactant components are poorly understood in this group. Additionally, up to 40% of survivors will develop bronchopulmonary dysplasia (BPD), but little is known about the contribution of continued surfactant dysfunction to its cause. Previous stable isotope incorporation methodologies have probed synthesis of the predominant surfactant phospholipids, but these require steadystate infusion, reflect fatty acid metabolism as well as phosphatidylcholine (PC) synthesis and provide limited information in terms of individual molecular species of PC.

Methods: Using tandem electrospray ionization mass spectrometry, with sequential endotracheal aspirate (ETA) and plasma samples, we have monitored the incorporation of methyl-D9 labelled choline (D9C) into the PC species of newborn premature infants. The method utilizes a short single infusion, with infants who remain ventilated at 120 hours after recruitment receiving a second dose of D9C. The incorporation into newly synthesized PC molecular species can therefore be monitored over time and directly reflects in vivo synthesis and secretion. As such, it is ideally suited to study mechanisms of surfactant PC synthesis, acyl remodelling and turnover. The dynamics of phosphatidylglycerol (PG) and phosphatidylinositol (PI) were analysed in parallel.

Results: Results from ventilated, preterm infants (n=24) are presented (see figure 1) and demonstrate rapid incorporation of D9C into plasma PC by 6 hours. In contrast, negligible incorporation was detectable in ETA PC for the first three days, despite continued presence of unlabelled PC. Additionally ETA data showed enrichment of PI and absence of exogenously derived PG.

Figure 1

Conclusion: These results demonstrate for the first time, that PC synthetic rates in the lungs and livers of newborn preterm infants differ markedly from that seen in older children and adults. The rapid incorporation into plasma PC indicates very active liver lipid synthesis. The changes to the composition of PI and PG suggest rapid recycling in the alveolar type 2 cell however the slow incorporation of D9C into the surfactant lipid pool suggests limited de novo synthesis. Synthetic rates vary widely between patients highlighting the potential for biochemical stratification and identification of individual patients who would benefit from targeted surfactant therapy to reduce the risk of developing BPD.

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