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Intestinal Epithelial Apoptosis initiates Gut Mucosal Injury during Extracorporeal Membrane Oxygenation in the Newborn Piglet
BACKGROUND: Neonates and young infants exposed to extracorporeal circulation during extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB) are at risk of developing a systemic inflammatory response syndrome (SIRS) with multi-organ dysfunction. We used a piglet model of ECMO to i...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946757/ https://www.ncbi.nlm.nih.gov/pubmed/24365747 http://dx.doi.org/10.1038/labinvest.2013.149 |
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author | MohanKumar, Krishnan Killingsworth, Cheryl R. McILwain, R. Britt Timpa, Joseph G. Jagadeeswaran, Ramasamy Namachivayam, Kopperuncholan Kurundkar, Ashish R. Kelly, David R. Garzon, Steven A. Maheshwari, Akhil |
author_facet | MohanKumar, Krishnan Killingsworth, Cheryl R. McILwain, R. Britt Timpa, Joseph G. Jagadeeswaran, Ramasamy Namachivayam, Kopperuncholan Kurundkar, Ashish R. Kelly, David R. Garzon, Steven A. Maheshwari, Akhil |
author_sort | MohanKumar, Krishnan |
collection | PubMed |
description | BACKGROUND: Neonates and young infants exposed to extracorporeal circulation during extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB) are at risk of developing a systemic inflammatory response syndrome (SIRS) 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. METHODS: Healthy 3-week-old piglets were subjected to ECMO for up to 8h. 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 was investigated by immunohistochemistry, Western blots, and reverse transcriptase-quantitative polymerase chain reaction. RESULTS: Piglet ECMO was associated with increased gut epithelial apoptosis. Extensive apoptotic changes were noted on villus tips and in scattered crypt cells after 2h of ECMO. After 8h, the villi were denuded and apoptotic changes were evident in a majority of crypt cells. Increased circulating I-FABP levels, a marker of gut epithelial injury, showed that epithelial injury occurred during ECMO. We detected increased cleaved caspase-8, but not cleaved caspase-9, in epithelial cells indicating that the extrinsic apoptotic pathway was active. ECMO was associated with increased fas ligand expression in intestinal mast cells, which was induced through activation of the p38 mitogen-activated protein kinase. CONCLUSIONS: Epithelial apoptosis is an early event that initiates gut mucosal injury in a piglet model of ECMO. |
format | Online Article Text |
id | pubmed-3946757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-39467572014-08-01 Intestinal Epithelial Apoptosis initiates Gut Mucosal Injury during Extracorporeal Membrane Oxygenation in the Newborn Piglet MohanKumar, Krishnan Killingsworth, Cheryl R. McILwain, R. Britt Timpa, Joseph G. Jagadeeswaran, Ramasamy Namachivayam, Kopperuncholan Kurundkar, Ashish R. Kelly, David R. Garzon, Steven A. Maheshwari, Akhil Lab Invest Article BACKGROUND: Neonates and young infants exposed to extracorporeal circulation during extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB) are at risk of developing a systemic inflammatory response syndrome (SIRS) 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. METHODS: Healthy 3-week-old piglets were subjected to ECMO for up to 8h. 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 was investigated by immunohistochemistry, Western blots, and reverse transcriptase-quantitative polymerase chain reaction. RESULTS: Piglet ECMO was associated with increased gut epithelial apoptosis. Extensive apoptotic changes were noted on villus tips and in scattered crypt cells after 2h of ECMO. After 8h, the villi were denuded and apoptotic changes were evident in a majority of crypt cells. Increased circulating I-FABP levels, a marker of gut epithelial injury, showed that epithelial injury occurred during ECMO. We detected increased cleaved caspase-8, but not cleaved caspase-9, in epithelial cells indicating that the extrinsic apoptotic pathway was active. ECMO was associated with increased fas ligand expression in intestinal mast cells, which was induced through activation of the p38 mitogen-activated protein kinase. CONCLUSIONS: Epithelial apoptosis is an early event that initiates gut mucosal injury in a piglet model of ECMO. 2013-12-23 2014-02 /pmc/articles/PMC3946757/ /pubmed/24365747 http://dx.doi.org/10.1038/labinvest.2013.149 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article MohanKumar, Krishnan Killingsworth, Cheryl R. McILwain, R. Britt Timpa, Joseph G. Jagadeeswaran, Ramasamy Namachivayam, Kopperuncholan Kurundkar, Ashish R. Kelly, David R. Garzon, Steven A. Maheshwari, Akhil Intestinal Epithelial Apoptosis initiates Gut Mucosal Injury during Extracorporeal Membrane Oxygenation in the Newborn Piglet |
title | Intestinal Epithelial Apoptosis initiates Gut Mucosal Injury during Extracorporeal Membrane Oxygenation in the Newborn Piglet |
title_full | Intestinal Epithelial Apoptosis initiates Gut Mucosal Injury during Extracorporeal Membrane Oxygenation in the Newborn Piglet |
title_fullStr | Intestinal Epithelial Apoptosis initiates Gut Mucosal Injury during Extracorporeal Membrane Oxygenation in the Newborn Piglet |
title_full_unstemmed | Intestinal Epithelial Apoptosis initiates Gut Mucosal Injury during Extracorporeal Membrane Oxygenation in the Newborn Piglet |
title_short | Intestinal Epithelial Apoptosis initiates Gut Mucosal Injury during Extracorporeal Membrane Oxygenation in the Newborn Piglet |
title_sort | intestinal epithelial apoptosis initiates gut mucosal injury during extracorporeal membrane oxygenation in the newborn piglet |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946757/ https://www.ncbi.nlm.nih.gov/pubmed/24365747 http://dx.doi.org/10.1038/labinvest.2013.149 |
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