Post remote ischaemic conditioning and early pre remote ischaemic conditioning reduces the extent and severity of bowel injury in an animal model of necrotising enterocolitis

Q: What is the clinical evidence from this study?

Population: Necrotising enterocolitis (intestinal ischaemia-reperfusion injury animal model) (n=98). Intervention: Remote ischaemic conditioning (RIC) via hind limb ligature vs. Intestinal ischaemia-reperfusion injury (IRI) alone (positive control) and sham surgery (negative control). Primary outcome: Microscopic severity of intestinal injury assessed by the Chiu-Park score (0-8 scale; reported for combined early+preRIC vs IRI alone) (p=0.0001).

Q: What does this research mean for the field?

Remote ischaemic conditioning reduces the extent and severity of intestinal ischaemia-reperfusion injury in rat pups, with two doses delivered 48 hours apart conferring the greatest protective effect. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Ian Howard Jones; Denise Tao; Bhumita Vagdama; Laurie C.K. Lau; Jane E. Collins; Nigel John Hall

doi:10.1007/s00383-026-06717-8

November 13, 2026Pediatric Surgery InternationalOpen Access

Post remote ischaemic conditioning and early pre remote ischaemic conditioning reduces the extent and severity of bowel injury in an animal model of necrotising enterocolitis

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Key result

Dual remote ischaemic conditioning reduces median intestinal injury by ~3 points on Chiu-Park scoring.

P=0.0001
n=98

Why the study?

Remote ischaemic conditioning has a protective effect in an experimental model of severe necrotising enterocolitis, prompting an investigation into the impact of delivering it at different time-points.

Does remote ischaemic conditioning delivered at different time-points (before, after, or 48 hours prior to injury) reduce the extent and severity of macroscopic and microscopic intestinal injury in a rat pup model of necrotising enterocolitis?

Key Points

To evaluate the impact of delivering remote ischaemic conditioning at different time points on the extent and severity of intestinal ischaemia-reperfusion injury in an animal model.
Rat pups aged 10–13 days were randomly assigned to sham surgery (n=10), intestinal ischaemia-reperfusion injury (IRI) alone (n=14), preRIC immediately before IRI (n=16), postRIC at the start of reperfusion (n=16), early preRIC 48 h before IRI (n=18), early+preRIC delivered both 48 h and immediately before IRI (n=16), or preRIC without IRI (n=8).
Intestinal IRI was induced by 40 minutes of superior mesenteric artery occlusion followed by 90 minutes of reperfusion; remote ischaemic conditioning was induced using a hind limb ligature across 3 cycles of 5 minutes ischaemia and 5 minutes reperfusion.
Macroscopic injury, microscopic Chiu-Park histological injury scores, and terminal serum cytokine concentrations were measured.
Severe macroscopic intestinal necrosis was significantly reduced from 78% (IQR 30–90%) with IRI alone to 4% (0–21%, p=0.0019) with preRIC, 4% (0–44%, p=0.0021) with postRIC, 3% (0–42%, p=0.0054) with early preRIC, and 0% (0–39%, p=0.0018) with early+preRIC.
Microscopic injury scores were reduced compared to IRI alone (5.5, IQR 4–6) in the preRIC group [3.5 (1.25–5, p=0.002)], postRIC group [4.25 (4–5, p=0.031)], and early+preRIC group [2.375 (1.625–3.4375, p=0.0001)], whereas early preRIC alone showed no significant reduction (p=0.17).
Circulating levels of IFN-γ, IL-4, and IL-5 increased following remote ischaemic conditioning.

Structured PICO

Does remote ischaemic conditioning delivered at different time-points (before, after, or 48 hours prior to injury) reduce the extent and severity of macroscopic and microscopic intestinal injury in a rat pup model of necrotising enterocolitis?

P

Population

98 rat pups aged 10-13 days in an experimental intestinal ischaemia-reperfusion injury model of necrotising enterocolitis, followed for 90 minutes post-reperfusion.

I

Intervention

Remote ischaemic conditioning (RIC) delivered via a hind limb ligature for 3 cycles of 5 minutes of ischaemia with 5 minutes of reperfusion between episodes, administered at different time-points: immediately prior to IRI (preRIC, n=16), at the beginning of the reperfusion phase (postRIC, n=16), 48 hours prior to injury (early preRIC, n=18), both 48 hours and immediately prior to injury (early+preRIC, n=16), or preRIC followed by sham surgery without IRI (n=8)

C

Comparator

Positive controls undergoing intestinal ischaemia-reperfusion injury (IRI) alone without RIC (n=14), and negative controls undergoing sham surgery (laparotomy and dissection of the superior mesenteric artery without clip application, n=10)

O

Outcome

Microscopic severity of bowel injury assessed using the validated Chiu-Park Score (0-8 scale) at 90 minutes post-reperfusion, evaluated by three blinded assessorssurrogate

Main Result

Absolute Event Rate: 2.375% vs 5.5%

p-value: p=0.0001

Remote ischaemic conditioning significantly reduces macroscopic and microscopic intestinal injury in a preclinical rat model of necrotising enterocolitis when given before or immediately after ischaemia, with two doses 48 hours apart providing the greatest protection.

Limitations

Preclinical animal model of intestinal ischaemia-reperfusion injury in rat pups does not fully replicate human necrotising enterocolitis
Macroscopic bowel injury assessment was not blinded
Post-RIC had to be administered under general anaesthesia, whereas pre-RIC and early-RIC were administered without anaesthesia
Small animal size precluded serial blood sampling at multiple time points in the same animal
The study was not powered for serum cytokine analyses
The intestinal ischaemia-reperfusion injury model does not fully represent human necrotising enterocolitis.
The study was not powered for the serum cytokine analyses, which require formal confirmation with a different study design allowing blood sampling at multiple time points.
Small size of rat pups only permitted serum collection via terminal cardiac puncture, preventing longitudinal sampling at multiple time points in the same animal.
Post-RIC had to be performed under general anaesthesia (a known confounder that may reduce RIC efficacy), whereas pre-RIC was performed prior to anaesthesia.
Pups that did not undergo pre-RIC were not separated from their dams, introducing a potential handling/separation confounder.

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Implication

RIC timing optimization attenuates injury in rat NEC model; leaves open translation to human neonates.

Abstract

Purpose Remote ischaemic conditioning (RIC) has a protective effect in an experimental model of severe necrotising enterocolitis. We investigated the impact of delivering RIC at different time-points. Methods We used an established intestinal ischaemia-reperfusion injury (IRI) model in rat pups. RIC was delivered by means of a lower limb ligature. Animals were randomly allocated to intestinal IRI only, RIC before IRI (preRIC), RIC after IRI (postRIC), RIC 48 h before IRI (earlyRIC), RIC 48 h and immediately before IRI (early + preRIC), or control. Macroscopic and microscopic intestinal injury are reported. Serum cytokine levels were assayed. Data are median (inter-quartile range). Results Animals receiving RIC had reduced severe macroscopic intestinal injury: pre-RIC 4% (0–21%, p = 0.0019), postRIC 4% (0–44%, p = 0.0021), earlyRIC 3% (0–42%, p = 0.0054) and early+preRIC 0% (0–39%, p = 0.0018) vs. IRI 78% (30–90). The preRIC and postRIC groups compared had reduced injury scores compared to IRI alone: 3.5 (1.25–5, p = 0.002) and 4.25 (4–5, p = 0.031) vs. 5.5 (4–6). RIC 48 h prior to IRI did not reduce injury but injury was lowest in early+preRIC group [2.375 (1.625–3) 0.4375, p = 0.0001]. IFN-γ, IL-4 and IL-5 were increased following RIC. Conclusion RIC reduces the extent and severity of intestinal injury. Two doses of RIC delivered 48 h apart has the greatest effect. Cytokines IFN-γ, IL-4 and IL-5 may be important in the transmission of RIC.

Discussion

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Cite This Study

Jones et al. (2026) studied Necrotising enterocolitis (intestinal ischaemia-reperfusion injury animal model) (n=98). Remote ischaemic conditioning (RIC) via hind limb ligature vs. Intestinal ischaemia-reperfusion injury (IRI) alone (positive control) and sham surgery (negative control) was evaluated on Microscopic severity of intestinal injury assessed by the Chiu-Park score (0-8 scale; reported for combined early+preRIC vs IRI alone) (p=0.0001). Remote ischaemic conditioning delivered 48 hours and immediately prior to ischaemia reduced median Chiu-Park bowel injury scores to injury alone.

synapsesocial.com/papers/6af88c410e4d8f4b089c1b1f https://doi.org/10.1007/s00383-026-06717-8

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Post remote ischaemic conditioning and early pre remote ischaemic conditioning reduces the extent and severity of bowel injury in an animal model of necrotising enterocolitis

Key Points

Structured PICO

Main Result

Limitations

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Implication

Abstract

Discussion

Cite This Study

Post remote ischaemic conditioning and early pre remote ischaemic conditioning reduces the extent and severity of bowel injury in an animal model of necrotising enterocolitis

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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