Evaluating Remote Ischemic Conditioning in a Rat Model of Intestinal Ischemia Reperfusion: A Study Highlighting Experimental Model Limitations

在大鼠肠缺血再灌注模型中评估远程缺血预适应:一项强调实验模型局限性的研究

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Abstract

CONTEXT: Remote ischemic conditioning (RIC) protects distant organs from ischemia-reperfusion injury (IRI) through brief, nonlethal ischemic episodes. In pediatric intestinal IRI, such as in midgut volvulus and necrotizing enterocolitis, RIC may enhance bowel viability and reduce the need for extensive resections. AIMS: This study aimed to evaluate the protective effects of RIC on intestinal IRI (IIRI) in a rat model by assessing histopathological changes, gene expression, and intestinal motility when RIC is applied during the ischemic or reperfusion phase. SETTINGS AND DESIGN: An experimental animal study conducted at a tertiary hospital, over 20 months. Twenty four male Wistar rats were employed and randomly assigned into four groups: Sham, IIRI, RIC during ischemia (RIperC), and RIC during reperfusion (RIpostC). SUBJECTS AND METHODS: Intestinal ischemia was induced by clamping mesenteric vessels for 45 min. RIC was performed through four cycles of 5-min hind limb occlusion followed by reperfusion, either during the intestinal ischemia (RIperC) or during the intestinal reperfusion (RIpostC) phase. Rats were sacrificed after 24 h of reperfusion, and intestinal tissues were analysed for histopathological changes, gene expression (interleukin-6, tumor necrosis factor-alpha, Ki-67, Bax, heme oxygenase-1), and motility patterns. RESULTS: Histopathological analysis did not reveal any signs of mucosal damage attributable to intestinal ischemia in any of the groups. Similarly, gene expression analysis did not demonstrate any statistically significant difference among the groups. Furthermore, no significant difference was detected in the contractility parameters. These findings indicate that our experimental model did not induce sufficient ischemia in the bowel to produce any histopathological or molecular changes. CONCLUSION: There is a lack of standardized protocols in intestinal ischemia-reperfusion models, leading to inconsistent results. Establishing a robust and standardized experimental model is essential before evaluating therapeutic interventions like RIC in intestinal IRI.

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