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Remote Ischaemic Conditioning As A Novel Therapeutic Intervention For Experimental Nec

Authors
Ian Jones, Jane Collins and Nigel Hall

Institution(s): University of Southampton. Tremona Road, Southampton, SO16 6YD. UK, Southampton Children’s Hospital. Tremona Road, Southampton, SO16 6YD. UK

Introduction
Necrotising enterocolitis (NEC) continues to be a cause of significant morbidity and mortality in preterm infants. Novel therapeutic or preventive interventions are desperately needed. We hypothesised that remote ischaemic conditioning (RIC) may be a useful therapeutic intervention for infants with NEC and aimed to evaluate the efficacy of RIC in an experimental NEC model based on intestinal ischaemia reperfusion injury (IRI).

Methods
With ethical approval (PA813F125), rat pups (10-13 days old) were anesthetised and underwent laparotomy with occlusion of the superior mesenteric artery (SMA) for 40 minutes followed by 90 minutes of reperfusion. RIC was applied by occluding hind limb blood flow for 3 cycles of 5 minutes immediately prior to anaesthesia. Control animals underwent laparotomy and exposure of the SMA without occlusion. Intestinal injury was assessed macroscopically, and microscopically using the Chui-Park scoring system (range 0-8).

Results
Intestine of control animals (n=10) was macroscopically normal. The length of intestine that showed any injury was significantly reduced in animals exposed to RIC prior to IRI (n=13) compared to those who had IRI alone with no RIC (n=14, median 100% [range 0-100] vs 49% [0-100]; p=0.008). The length of intestine with severe necrosis was also shorter in animals exposed to RIC (RIC+IRI 0% (0-55%) vs IRI 40% (0-100%); p=0.002)
Blinded microscopic assessment of intestine demonstrated a significantly reduced injury score in the RIC+IRI group compared to IRI alone. Median score 4 [range 0-6] vs 6 4-7.

Conclusions
In this animal model of NEC, RIC shows a significant protective effect against both the extent and the severity of intestinal injury. RIC should be explored as a potential treatment option for human NEC.

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