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

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, Richard Y. Wu, Mikihiro Inoue, Keiichi Uchida, Masato Kusunoki, Paul Delgado-Olguin, Luc Mertens, Alan Daneman, Simon Eaton, Philip M. Sherman and Agostino Pierro ()
Additional contact information
Yuhki Koike: The Hospital for Sick Children
Bo Li: The Hospital for Sick Children
Niloofar Ganji: The Hospital for Sick Children
Haitao Zhu: The Hospital for Sick Children
Hiromu Miyake: The Hospital for Sick Children
Yong Chen: The Hospital for Sick Children
Carol Lee: The Hospital for Sick Children
Maarten Janssen Lok: The Hospital for Sick Children
Carlos Zozaya: The Hospital for Sick Children
Ethan Lau: The Hospital for Sick Children
Dorothy Lee: The Hospital for Sick Children
Sinobol Chusilp: The Hospital for Sick Children
Zhen Zhang: The Hospital for Sick Children
Masaya Yamoto: The Hospital for Sick Children
Richard Y. Wu: Hospital for Sick Children
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
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
Agostino Pierro: The Hospital for Sick Children

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18750-9

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