Jones, IH;
Tao, D;
Vagdama, B;
Orford, M;
Eaton, S;
Collins, J;
Hall, NJ;
(2023)
Remote Ischaemic Pre-conditioning Reduces Intestinal Ischaemia Reperfusion Injury in a Newborn Rat.
Journal of Pediatric Surgery
, 58
(7)
pp. 1389-1398.
10.1016/j.jpedsurg.2022.11.014.
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Abstract
Objective: Remote ischaemic conditioning (RIC) has been shown to reduce ischaemia-reperfusion injury(IRI) in multiple organ systems. IRI is seen in multiple bowel pathologies in the newborn, including NEC. We investigated the potential of RIC as a novel therapy for various intestinal pathologies in the newborn. / Methods: We used an established intestinal IRI model in rat pups which results in similar intestinal injury to necrotising enterocolitis (NEC). Animals were randomly allocated to IRI only(n = 14), IRI + RIC(n = 13) or sham laparotomy(n = 10). The macroscopic extent of intestinal injury is reported as a percentage of total small bowel. Injury severity was measured using Chiu-Park scoring. Neutrophil infiltration/activation was assayed by myeloperoxidase activity. Immunohistochemistry was used to assess the expression of hypoxia-inducible factor alpha (HIF-1α). Data are median (interquartile range). / Results: Animals that underwent RIC showed a decreased extent of macroscopic injury from 100%(85–100%) in the IRI only group to 58%(15–84%, p = 0.003) in the IRI + RIC group. Microscopic injury score was significantly lower in animals that underwent RIC compared to IRI alone (3.5[1.25–5] vs 5.5[4–6], p = 0.014). Intestinal myeloperoxidase activity in animals exposed to IRI was 3.4 mU/mg of tissue (2.5–3.7) and 2.1 mU/mg(1.5–2.8) in the IRI + RIC group(p = 0.047). HIF-1α expression showed a non-significant trend towards reduced expression in the IRI + RIC group. / Conclusions: RIC reduces the extent and severity of bowel injury in this animal model, supporting the hypothesis that RIC has therapeutic potential for intestinal diseases in the newborn.
| Type: | Article |
|---|---|
| Title: | Remote Ischaemic Pre-conditioning Reduces Intestinal Ischaemia Reperfusion Injury in a Newborn Rat |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jpedsurg.2022.11.014 |
| Publisher version: | https://doi.org/10.1016/j.jpedsurg.2022.11.014 |
| Language: | English |
| Additional information: | Copyright © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Keywords: | NEC, Necrotising enterocolitis, Intestinal ischaemia, RIC, Remote ischaemic conditioning |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10161247 |
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