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Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage in experimental necrotizing enterocolitis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
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2012 (English)In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 47, no 9, 1646-1651 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/PURPOSE:

Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants and carries significant morbidity and mortality. There is a great need for improved diagnostic methods to reduce the severity and incidence of NEC. The aim of the study was to investigate if intraluminal microdialysis can detect intestinal ischemia in newborn rats with induced experimental NEC.

METHODS:

The studies were performed on 1-day-old Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment. Microdialysis catheters were rectally inserted and placed in the rectosigmoid part of the colon. Microdialysate levels of glucose, lactate, pyruvate, and glycerol were measured. Intestinal specimens were collected at the end of the experiments for microscopic evaluation.

RESULTS:

Intraluminal microdialysis revealed signs of intestinal hypoxia and cellular damage, with a marked increase of lactate and glycerol. Microscopic evaluation confirmed intestinal damage in the NEC group.

CONCLUSION:

Intraluminal microdialysis can detect intestinal hypoxic stress and mucosal cell membrane decay in a rat model of NEC. Intestinal intraluminal microdialysis is easily accessible through the rectum and may be a useful noninvasive complement to other methods in the assessment of NEC.

Place, publisher, year, edition, pages
2012. Vol. 47, no 9, 1646-1651 p.
National Category
Surgery
Research subject
Pediatric Surgery
Identifiers
URN: urn:nbn:se:uu:diva-183821DOI: 10.1016/j.jpedsurg.2012.03.086ISI: 000308810400013PubMedID: 22974600OAI: oai:DiVA.org:uu-183821DiVA: diva2:564535
Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Experimental and Clinical Necrotizing Enterocolitis
Open this publication in new window or tab >>Experimental and Clinical Necrotizing Enterocolitis
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Necrotizing enterocolitis (NEC), a severe inflammatory disorder of the gastrointestinal tract with high morbidity and mortality, affects primarily preterm infants. The diagnosis represents a challenging task, and no biomarker has been found to aid early diagnosis with high accuracy. Microdialysis has been widely used to detect metabolites of anaerobic metabolism, enabling a local and early detection of ischemia. This thesis aims to evaluate the possibility of detecting intestinal ischemic stress in experimental and clinical  NEC, by use of rectal intraluminal microdialysis.

Intraluminal rectal microdialysis was performed on rats subjected to total intestinal ischemia. Metabolites of ischemia were detectable in both ileum and rectum, with raised glycerol concentrations and lactate/pyruvate ratios. Elevated concentrations of glycerol correlated to increasing intestinal histopathological injury.

Experimental early NEC was induced in newborn rat pups, by hypoxia/re-oxygenation treatment. Development of NEC was confirmed by histopathology. Elevated glycerol concentrations were detected by rectal microdialysis.

The genetic alterations following experimental NEC in rat pups were studied with microarray. Immunohistochemistry staining was performed for tight junction proteins claudin-1 and claudin-8. Several genes were altered in experimental NEC, mainly genes regulating tight junctions and cell adhesion. Immunohistochemistry revealed reduced expression of claudin-1.

A prospective study was conducted on preterm infants with a gestational age of less than 28 weeks. The infants were admitted to a neonatal intensive care unit, and observed during a 4-week period. Rectal microdialysis was performed twice a week, and blood was drawn for analysis of I-FABP. A total of 15 infants were included in the study, whereof four infants developed NEC, and 11 served as controls. Rectal glycerol and I-FABP displayed high concentrations, which varied considerably during the observation periods, both in NEC and controls. No differences in either glycerol or I-FABP concentrations were seen in the NEC-group vs. the controls.

In conclusion, rectal microdialysis can detect metabolites of intestinal ischemia, both in experimental and clinical NEC. Rectal microdialysis is safe and could provide a valuable non-invasive aid to detect hypoxia-induced intestinal damage or ischemic stress in extremely preterm infants. In this study however, it was not possible to predict the development of clinical NEC using microdialysis or I-FABP.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 898
Keyword
Necrotizing, Enterocolitis, Ischemia, Microdialysis, Intraluminal, I-FABP
National Category
Surgery
Research subject
Pediatric Surgery
Identifiers
urn:nbn:se:uu:diva-197754 (URN)978-91-554-8655-6 (ISBN)
Public defence
2013-05-30, Rosénsalen, Ing 95/96, NB, Akademiska Barnsjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2013-05-06 Created: 2013-04-03 Last updated: 2013-08-30Bibliographically approved

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Högberg, NiclasCarlsson, Per-OlaHillered, LarsStenbäck, AndersEngstrand Lilja, Helene

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