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Remote Ischaemic Pre-Conditioning Reduces Intestinal Ischaemia Reperfusion Injury in a Newborn Rat
Ian Howard Jones1, Denise Tao2, Bhumita Vagdama2
1Department of Paediatric Surgery and Urology, Southampton Children's Hospital, Southampton, UK; University Surgery Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Insights
Remote ischaemic conditioning (RIC) significantly reduced bowel injury in a newborn rat model. This novel therapy shows promise for treating intestinal diseases in infants, decreasing both macroscopic and microscopic damage.
Area of Science:
- Neonatal Medicine
- Surgical Research
- Gastroenterology
Background:
- Ischaemia-reperfusion injury (IRI) significantly impacts neonatal bowel pathologies, notably necrotising enterocolitis (NEC).
- Remote ischaemic conditioning (RIC) is a potential therapeutic strategy for mitigating IRI across various organ systems.
Purpose of the Study:
- To investigate the therapeutic efficacy of RIC in reducing intestinal injury in a neonatal model.
- To evaluate RIC's potential as a novel treatment for neonatal intestinal diseases.
Main Methods:
- An established rat pup intestinal IRI model, mimicking necrotising enterocolitis (NEC), was utilized.
- Animals were randomized into three groups: IRI only, IRI + RIC, and sham laparotomy.
- Macroscopic injury, microscopic severity (Chiu-Park scoring), neutrophil infiltration (myeloperoxidase activity), and HIF-1α expression were assessed.
Main Results:
- RIC significantly decreased macroscopic intestinal injury extent (58% vs. 100% in IRI only group, p=0.003).
- Microscopic injury scores were significantly lower in the RIC group compared to IRI alone (p=0.014).
- Intestinal myeloperoxidase activity was reduced with RIC, indicating decreased neutrophil infiltration (p=0.047).
Conclusions:
- Remote ischaemic conditioning effectively reduces the extent and severity of bowel injury in this neonatal animal model.
- These findings support RIC as a promising therapeutic candidate for neonatal intestinal diseases.
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.
