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Large Animal Models Enhance the Study of Crypt-Mediated Epithelial Recovery From Prolonged Intestinal Ischemia Reperfusion Injury
McKinney-Aguirre et al., American Journal of Physiology-Gastrointestinal and Liver Physiology. 2024.
https://pubmed.ncbi.nlm.nih.gov/39404771/
Intestinal ischemia and reperfusion injury (IRI) is a severe pathological alteration that compromises the intestinal epithelial barrier, causing bacterial translocation, shock, sepsis, and potentially death. Preclinical research for IRI has focused on utilizing murine models, but mice demonstrate key anatomical and physiological intestinal differences from humans, such as tissue enzymes, intestinal permeability, and hypoxic response pathways. The researchers compared a 3-hour IRI porcine model to a 3-hour IRI murine model to reveal which demonstrated a stronger translational capacity. Both models demonstrated crypt damage, but only the porcine model showed recovery-associated crypt death expansion and re-epithelialization. At 72 hours post-IRI, mouse mortality was 84.6%, whereas porcine mortality was 0%. A porcine model would be more reliable for future translational studies focused on understanding IRI mechanisms for diagnosis and therapy advancements. Supported by ORIP (T32OD011130, K01OD010199, R03OD026598) and NIDDK.