Heterogeneous Pulmonary Response After Tracheal Occlusion: Clues to Fetal Lung Growth.

Authors:
Evgenia Dobrinskikh
Evgenia Dobrinskikh
University of Colorado
United States
Saif I Al-Juboori
Saif I Al-Juboori
University of Colorado Denver
United States
Uladzimir Shabeka
Uladzimir Shabeka
University of Colorado Denver
United States
Julie A Reisz
Julie A Reisz
Wake Forest University
United States
Connie Zheng
Connie Zheng
Teleosis Institute
United States
Ahmed I Marwan
Ahmed I Marwan
University of Colorado Denver

J Surg Res 2019 Jul 8;239:242-252. Epub 2019 Mar 8.

Division of Pediatric Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado. Electronic address:

Background: Understanding inconsistent clinical outcomes in infants with severe congenital diaphragmatic hernia (CDH) after tracheal occlusion (TO) is a crucial step for advancing neonatal care. The objective of this study is to explore the heterogeneous airspace morphometry and the metabolic landscape changes in fetal lungs after TO.

Methods: Fetal lungs on days 1 and 4 after TO were examined using mass spectrometry-based metabolomics, fluorescence lifetime imaging microscopy (FLIM), the number of airspaces, and tissue-to-airspace ratio (TAR).

Results: Two morphometric areas were identified in TO lungs compared with controls (more small airspaces at day 1 and a higher number of enlarged airspaces at day 4). Global metabolomics analysis revealed a significant upregulation of glycolysis and a suppression of the tricarboxylic acid cycle in day 4 TO lungs compared with day 1 TO lungs. In addition, there was a significant increase in polyamines involved in cell growth and proliferation. Locally, FLIM analysis on day 1 TO lungs demonstrated two types of heterogeneous zones-similar to control and with increased oxidative phosphorylation. FLIM on day 4 TO lungs demonstrated appearance of zones with enlarged airspaces and a metabolic shift toward glycolysis, accompanied by a decrease in the FLIM "lipid-surfactant" signal.

Conclusions: In normal fetal lungs, we report a novel temporal pattern of varied morphometric and metabolic changes. Initially, there is formation of zones with small airspaces, followed by airspace enlargement over time. Metabolically day 1 TO lungs have zones with increased oxidative phosphorylation, whereas day 4 TO lungs have a shift toward glycolysis in the enlarged airspaces. Based on our observations, we speculate that the "best responders" to tracheal occlusion should have bigger lungs with small airspaces and normal surfactant production.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2019.02.015DOI Listing
July 2019
4 Reads

Publication Analysis

Top Keywords

day lungs
24
small airspaces
12
tracheal occlusion
12
fetal lungs
12
enlarged airspaces
12
lungs
11
airspaces day
8
day
8
oxidative phosphorylation
8
shift glycolysis
8
lungs demonstrated
8
increased oxidative
8
lungs compared
8
airspaces
7
polyamines involved
4
involved cell
4
heterogeneous zones-similar
4
control increased
4
increase polyamines
4
cell growth
4

Similar Publications