Remote ischemic conditioning avoids the development of intestinal damage after ischemia reperfusion by reducing intestinal inflammation and increasing intestinal regeneration

Abstract

Aim of the study

Midgut volvulus is a potentially life-threatening condition which is based on intestinal ischemia and reperfusion (I/R) injury. Remote ischemia conditioning (RIC) applied to a limb can protect distant organs such as heart and kidney. The aims of this study were to investigate the effect of RIC on a model of midgut volvulus and to explore its underlying mechanism of action.

Methods

Six-weeks old C57BL/6 mice were studied: (a) sham (n = 4): laparotomy alone. (b) Intestinal I/R injury (n = 5): occlusion of the superior mesenteric artery (SMA) for 45 min followed by reperfusion. (c) Intestinal I/R (as in group above) with RIC immediately after reperfusion (n = 5). RIC consisted of 4 cycles of 5 min hind limb ischemia followed by 5 min reperfusion. 24-h after laparotomy, animals were euthanized, and the small intestine (same distance from cecum) was harvested. The intestine was examined for inflammatory cytokines (TNF-α and IL-6), epithelial proliferation marker Ki67 and stem cell marker Lgr5 expression.

Main results

Compared to sham, the small intestine of IR mice had more intestinal damage, increased expression of inflammatory cytokines, decreased intestinal proliferation and stem cell activity. RIC significantly counteracted all these changes.

Conclusions

Remote ischemia conditioning avoids intestinal damage due to I/R injury. This beneficial effect is associated with decreased intestinal inflammation and enhanced intestinal regeneration. This study implicates that RIC is a novel non-invasive intervention to reduce the intestinal damage occurring in midgut volvulus.

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Acknowledgements

Dr. Agostino Pierro was supported by the Canadian Institutes of Health Research (CHIR) Foundation Grant (353857).

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Correspondence to Agostino Pierro.

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Zhu, H., Li, B., Bindi, E. et al. Remote ischemic conditioning avoids the development of intestinal damage after ischemia reperfusion by reducing intestinal inflammation and increasing intestinal regeneration. Pediatr Surg Int 37, 333–337 (2021). https://doi.org/10.1007/s00383-020-04831-9

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Keywords

  • Remote ischemic conditioning
  • Midgut volvulus
  • Intestinal damage
  • Ischemia and reperfusion
  • Neonate