Injury and repair in the very immature lung following brief mechanical ventilation

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Abstract

Mechanical ventilation (MV) of very premature infants contributes to lung injury and bronchopulmonary dysplasia (BPD), the effects of which can be long-lasting. Little is currently known about the ability of the very immature lung to recover from ventilator- induced lung injury. Our objective was to determine the ability of the injured very immature lung to repair in the absence of continued ventilation and to identify potential mechanisms. At 125 days gestational age (d GA, 0.85 of term) fetal sheep were partially exposed by hysterectomy under anesthesia and aseptic conditions; they were intubated and ventilated for 2 hours with an injurious MV protocol, and then returned to the uterus to continue development. Necropsy was performed at either 1d (short-term group, 126d GA, n=6) or 15d after MV (long-term group, 140d GA, n=5); controls were unventilated (n=7-8). At 1d after MV, lungs displayed signs of injury including hemorrhage, disorganised elastin and collagen deposition in the distal airspaces, altered morphology, significantly reduced secondary crest density and decreased air space. Bronchioles had thickened epithelium with evidence of injury and sloughing. Relative mRNA levels of early response genes (CTGF, CYR-61 and EGR-1) and pro-inflammatory cytokines (IL-1ss, IL-6, IL-8, TNF-alpha, TGF-ss) were not different between groups 1d after MV. At 15d after MV, lung structure was normal with no evidence of injury. We conclude that 2h of MV induces severe injury in the very immature lung, and that these lungs have the capacity to repair spontaneously in the absence of further ventilation.
Original languageEnglish
Pages (from-to)L917 - L926
Number of pages10
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number6
DOIs
Publication statusPublished - 2011

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