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      Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation

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          Abstract

          Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC.

          Abstract

          Necrotizing enterocolitis (NEC) is one of the most lethal gastrointestinal emergencies in neonates needing precision treatment. Here the authors show that remote ischemic conditioning is a non-invasive therapeutic method that enhances blood flow in the intestine, reduces damage, and improves NEC outcome.

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          Most cited references86

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          Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.

          Circulation, 74(5), 1124-1136
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            Necrotizing enterocolitis.

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              Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.

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                Author and article information

                Contributors
                agostino.pierro@sickkids.ca
                Journal
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                2 October 2020
                2 October 2020
                2020
                : 11
                : 4950
                Affiliations
                [1 ]GRID grid.42327.30, ISNI 0000 0004 0473 9646, Translational Medicine Program, , The Hospital for Sick Children, ; Toronto, ON Canada
                [2 ]GRID grid.42327.30, ISNI 0000 0004 0473 9646, Division of General and Thoracic Surgery, Translational Medicine, , The Hospital for Sick Children, ; Toronto, ON Canada
                [3 ]GRID grid.260026.0, ISNI 0000 0004 0372 555X, Departments of Gastrointestinal and Pediatric Surgery, , Mie University Graduate School of Medicine, ; Tsu, Japan
                [4 ]GRID grid.42327.30, ISNI 0000 0004 0473 9646, Division of Neonatology, , The Hospital for Sick Children, ; Toronto, ON Canada
                [5 ]GRID grid.42327.30, ISNI 0000 0004 0473 9646, Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, , Hospital for Sick Children, ; Toronto, ON Canada
                [6 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, , University of Toronto, ; Toronto, ON Canada
                [7 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Molecular Genetics, , University of Toronto, ; Toronto, ON Canada
                [8 ]GRID grid.423576.1, Heart & Stroke Richard Lewar Centre of Excellence, ; Toronto, ON Canada
                [9 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, The Labatt Family Heart Center, Cardiology, The Hospital for Sick Children, , University of Toronto, ; Toronto, ON Canada
                [10 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Diagnostic Imaging, Division of Nuclear Medicine, The Hospital for Sick Children, , University of Toronto, ; Toronto, ON Canada
                [11 ]GRID grid.83440.3b, ISNI 0000000121901201, UCL Great Ormond Street Institute of Child Health, ; London, UK
                [12 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Faculty of Dentistry, , University of Toronto, ; Toronto, ON Canada
                [13 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Surgery, , University of Toronto, ; Toronto, ON Canada
                Author information
                http://orcid.org/0000-0002-8298-8344
                http://orcid.org/0000-0003-0062-9258
                http://orcid.org/0000-0001-6473-0385
                http://orcid.org/0000-0002-5355-247X
                http://orcid.org/0000-0003-0892-9204
                http://orcid.org/0000-0002-4733-6690
                http://orcid.org/0000-0002-6742-6570
                Article
                18750
                10.1038/s41467-020-18750-9
                7532542
                33009377
                82ae7014-d2ee-4224-9ef9-c9a4f28e80e9
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 January 2019
                : 9 September 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100006126, Hospital for Sick Children (SickKids);
                Award ID: Restracomp Fellowship
                Award ID: Restracomp Fellowship
                Award ID: Operational Funds
                Award ID: Robert M. Filler Chair of Surgery
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000024, Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada);
                Award ID: 162208
                Award ID: Foundation Grant 353857
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000038, Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada);
                Award ID: 500865
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100004411, Heart and Stroke Foundation of Canada (Heart and Stroke Foundation);
                Award ID: G-17–0018613
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000272, DH | National Institute for Health Research (NIHR);
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                blood flow,gastrointestinal diseases
                Uncategorized
                blood flow, gastrointestinal diseases

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