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

Author:

Koike Yuhki,Li BoORCID,Ganji Niloofar,Zhu Haitao,Miyake Hiromu,Chen Yong,Lee Carol,Janssen Lok Maarten,Zozaya CarlosORCID,Lau Ethan,Lee Dorothy,Chusilp SinobolORCID,Zhang Zhen,Yamoto Masaya,Wu Richard Y.,Inoue Mikihiro,Uchida Keiichi,Kusunoki Masato,Delgado-Olguin PaulORCID,Mertens Luc,Daneman Alan,Eaton SimonORCID,Sherman Philip M.ORCID,Pierro AgostinoORCID

Abstract

AbstractNecrotizing 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.

Funder

Hospital for Sick Children

Gouvernement du Canada | Canadian Institutes of Health Research

Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada

Heart and Stroke Foundation of Canada

DH | National Institute for Health Research

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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