245 - Postnatal Growth Restriction Alters Rat Lung DHA and ARA Partitioning in Association with Impaired Lung Mechanics

Poster Number: 245
Publication Number: 245.339

Adrienne Cohen, University of Utah, Salt Lake City, UT, United States; Sophie C. Hochhauser, University of Utah, Salt Lake City, UT, United States; Ryan Gage, University of Utah School of Medicine, Springville, UT, United States; Haimei Wang, University of utah, Salt Lake City, UT, United States; Alan Maschek, University of Utah, Salt Lake City, UT, United States; Lisa .. Joss-Moore, University of Utah School of Medicine, Salt Lake City, UT, United States

Background: Growth restriction predisposes preterm neonates to increased risk of bronchopulmonary dysplasia (BPD). Decades of clinical and animal studies implicate low circulating levels of docosahexaenoic acid (DHA) in the pathogenesis of BPD. However, clinical trials show that direct supplementation of neonates with DHA does not improve BPD incidence and may increase BPD in some neonates. To understand the link between circulating DHA and other relevant fatty acids such as Arachidonic Acid (ARA) in the development of BPD, an understanding of lipid species within the lung is needed. We previously showed that growth restriction in the rat impairs alveolar formation, similar to BPD, in association with reduced circulating DHA. However, how growth restriction alters DHA and ARA within the lung, and whether altered fatty acid status is associated with impaired lung mechanics, is unknown.

Objective: We hypothesize that growth restriction in the rat alters DHA and ARA incorporation into lung lipid classes and that the alteration is associated with impaired lung mechanics.

Design/Methods: Postnatal growth restriction (PGR) was induced in rats by increased litter size (16 pups/litter vs 8 pups/litter for Con). PGR was applied to rats with normal prenatal growth (Con) or intrauterine growth restriction (IUGR- induced by bilateral uterine artery ligation). At postnatal day 12 lung lipids were characterized using untargeted lipidomics; some rats underwent lung mechanics testing using the Flexivent®. Male and female were treated as separate groups and differences were assessed by one-way ANOVA and Fishers post hoc test.

Results: In the rat lung, DHA and ARA were primarily located in the triglyceride (TG) fraction. DHA was also prevalent in the phosphatidylcholine (PC) fraction. In male rat lung, PGR did not alter total lung DHA or ARA, or DHA or ARA in TG, regardless of prenatal growth status. PGR increased DHA in PC (132±8%*) in the male rat lung. In female rat lung, PGR reduced total lung DHA (84±8%*) and increased DHA (131±20%*) and ARA (123±9%*) in TG, without altering DHA in PC. In male rats, PGR reduced lung compliance (64±9%*) and increased parenchymal lung resistance (157±17%*), regardless of prenatal growth status. In female rats, PGR did not alter lung mechanics. *P< 0.05

Conclusion(s): Postnatal growth restriction in the rat alters DHA and ARA incorporation into lung lipid classes in both male and female rat pups. In male rat pups, increased DHA in the PC fraction was associated with impaired lung mechanics, while in female rat pups, increased DHA and ARA in the TG fraction was associated with normal lung function.