Limited Effect of Remote Ischemic Preconditioning on Survival in Rodent Models of Sepsis

초록

Introduction: Sepsis is a severe pathological crisis marked by infection and systemic inflammation with high mortality rates. Sepsis induces microcirculatory dysfunction and oxidative stress, which share pathophysiological features with ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC), a method involving brief repeated cycles of limb ischemia and reperfusion, has been investigated as a potential strategy to improve outcomes in ischemia-reperfusion injury. Methods: This study aimed to examine the effect of RIPC on survival and serum chemical tests in two rat sepsis models. A total of 130 male Sprague-Dawley rats were used. The endotoxemia model was induced by intraperitoneal lipopolysaccharide (LPS) injection, and the peritonitis model was induced by cecal ligation and puncture (CLP). Serum chemical levels including total bilirubin, platelet count, blood urea nitrogen, creatinine, and lactate were measured according to the sepsis criteria. Results: In the LPS model, survival rates were 100% in control and RIPC-only groups, but decreased to 50% in the LPS group and 10% in the RIPC/LPS group (P = 0.012 and P < 0.001 versus control). In the CLP model, survival rates were 60% in both CLP and RIPC/CLP groups (P = 1.000). RIPC did not improve overall survival. While serum creatinine levels improved slightly in the RIPC/CLP group, other biochemical markers were unaffected by RIPC. Conclusions: Despite previous evidence in mice and sheep, RIPC did not improve survival or serum markers in rat sepsis models. The lack of benefit may reflect interspecies differences and highlights the need for further investigation before applying RIPC clinically in human sepsis. © 2025 Elsevier B.V., All rights reserved.

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