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

Author

Listed:
  • Yuhki Koike

    (The Hospital for Sick Children
    The Hospital for Sick Children
    Mie University Graduate School of Medicine)

  • Bo Li

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Niloofar Ganji

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Haitao Zhu

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Hiromu Miyake

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Yong Chen

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Carol Lee

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Maarten Janssen Lok

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Carlos Zozaya

    (The Hospital for Sick Children)

  • Ethan Lau

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Dorothy Lee

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Sinobol Chusilp

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Zhen Zhang

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Masaya Yamoto

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Richard Y. Wu

    (Hospital for Sick Children
    University of Toronto)

  • Mikihiro Inoue

    (Mie University Graduate School of Medicine)

  • Keiichi Uchida

    (Mie University Graduate School of Medicine)

  • Masato Kusunoki

    (Mie University Graduate School of Medicine)

  • Paul Delgado-Olguin

    (The Hospital for Sick Children
    University of Toronto
    Heart & Stroke Richard Lewar Centre of Excellence)

  • Luc Mertens

    (University of Toronto)

  • Alan Daneman

    (University of Toronto)

  • Simon Eaton

    (UCL Great Ormond Street Institute of Child Health)

  • Philip M. Sherman

    (Hospital for Sick Children
    University of Toronto)

  • Agostino Pierro

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

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.

Suggested Citation

  • Yuhki Koike & Bo Li & Niloofar Ganji & Haitao Zhu & Hiromu Miyake & Yong Chen & Carol Lee & Maarten Janssen Lok & Carlos Zozaya & Ethan Lau & Dorothy Lee & Sinobol Chusilp & Zhen Zhang & Masaya Yamoto, 2020. "Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18750-9
    DOI: 10.1038/s41467-020-18750-9
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