Remote Ischaemic Pre-Conditioning Reduces Intestinal Ischaemia Reperfusion Injury in a Newborn Rat.

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.