Intestinal epithelial apoptosis initiates gut mucosal injury during extracorporeal membrane oxygenation in the newborn piglet

Laboratory Investigation; a Journal of Technical Methods and Pathology
Krishnan MohanKumarAkhil Maheshwari

Abstract

Neonates and young infants exposed to extracorporeal circulation during extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass are at risk of developing a systemic inflammatory response syndrome with multi-organ dysfunction. We used a piglet model of ECMO to investigate the hypothesis that epithelial apoptosis is an early event that precedes villous damage during ECMO-related bowel injury. Healthy 3-week-old piglets were subjected to ECMO for up to 8 h. Epithelial apoptosis was measured in histopathological analysis, nuclear imaging, and terminal deoxynucleotidyl transferase dUTP nick end labeling. Plasma intestinal fatty acid-binding protein (I-FABP) levels were measured by enzyme immunoassay. Intestinal mast cells were isolated by fluorescence-assisted cell sorting. Cleaved caspase-8, caspase-9, phospho-p38 MAPK, and fas ligand expression were investigated by immunohistochemistry, western blots, and reverse transcriptase-quantitative PCR. Piglet ECMO was associated with increased gut epithelial apoptosis. Extensive apoptotic changes were noted on villus tips and in scattered crypt cells after 2 h of ECMO. After 8 h, the villi were denuded and apoptotic changes were evident in a majority of crypt cells. Increase...Continue Reading

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Citations

Jul 21, 2015·Journal of Vascular Surgery·Paula Rosalie KeschenauJohannes Kalder
Nov 29, 2016·Expert Review of Medical Devices·Gengo SunagawaKiyotaka Fukamachi
Oct 16, 2018·The Journal of Clinical Investigation·Milena ArmackiThomas Seufferlein
Aug 4, 2019·Nature Communications·Krishnan MohanKumarAkhil Maheshwari
May 6, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kopperuncholan NamachivayamAkhil Maheshwari
Aug 18, 2018·Mediators of Inflammation·Veronika VítkováJan Janota

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Methods Mentioned

BETA
FACS
PCR
flow cytometry

Software Mentioned

Sigma Stat
Image J
Beacon Design

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis