Midgut volvulus adds a neutrophil-driven model of murine sepsis to the experimental hyperinflammation toolbox

Abstract Background: Severe infections that culminate in sepsis are associated with high morbidity and mortality. Despite continuous efforts in basis science and clinical research, evidence based-therapy is mostly limited to basic causal and supportive measures. Adjuvant therapies, often remain without clear evidence. The objective of this study was to evaluate the volvulus-sepsis model and to compare it with two established murine sepsis models. Methods: The technique of the murine model of midgut volvulus was optimized and was compared to two established models of murine sepsis, namely ceacal ligation and puncture (CLP) and i.p. Injection of lipopolysaccharide (LPS). Results: Midgut volvulus for 15 minutes caused a comparable mortality (40%) as CLP (55%) and peritoneal LPS injection (25%) at 48h. Oxidative stress was comparable, cfDNA, and splenic/hepatic and pulmonary translocation of bacteria were decreased and increased, respectively. DNases were increased compared to the established models. Proteomic analysis revealed Epo, IL1b, Prdx5, Parp1, Ccl2 and IL6 to be upregulated at 48h in comparison to the healthy controls. Discussion and Conclusion: Midgut volvulus is a stable and physiological model for sepsis. Depending on the duration and subsequent tissue damage, it represents a combination of ischemia-reperfusion injury and hyperinflammation.