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Abstract

Objectives: To characterize time-dependent and regionally-specific injury patterns associated with early ventilation of the preterm lung using a mass-spectrometry based proteomic approach.Methods: Preterm lambs delivered at gestational age 124-127d were randomized to receive 15-min (n=7) or 90-min (n=10) of mechanical ventilation at standardized settings (positive end-expiratory pressure 8 cmH2O, tidal volume 6-8 mL/kg) and were compared with unventilated control lambs (n=7). At study completion, lung tissue was taken from standardized gravity-dependent and non-dependent regions, and assessed for lung injury via histology, qPCR and by proteomic analysis via Orbitrap-mass spectrometry. Ingenuity Pathway Analysis Software was used to identify temporal and region-specific enrichments in pathways and functions.Measurements and Main Results: Apoptotic cell numbers were 9-fold higher in non-dependent lung at 15- and 90-minutes compared to controls, whilst proliferative cells were increased 4-fold in the dependent lung at 90-minutes. The relative gene expression of lung injury markers was increased at 90-minutes in non-dependent lung (pConclusions: Complex injury pathways are initiated within the preterm lung after 15 minutes of ventilation and amplified by continuing ventilation. Injury development is region-specific with greater alterations within the proteome of non-dependent lung.

Item Type:	Article
Authors/Creators:	Pereira-Fantini, PM and Pang, B and Byars, SG and Oakley, RB and Perkins, EJ and Dargaville, PA and Davis, PG and Nie, S and Williamson, NA and Ignjatovic, V and Tingay, DG
Journal or Publication Title:	American Journal of Respiratory Cell and Molecular Biology
Publisher:	American Thoracic Society
ISSN:	1535-4989
DOI / ID Number:	10.1165/rcmb.2019-0084OC
Copyright Information:	Copyright © 2019 by the American Thoracic Society
Related URLs:	UTAS Profile: Dargaville, PA
Item Statistics:	View statistics for this item

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