A robust scoring system to evaluate sepsis severity in an animal model

被引：352

作者：

Shrum B. ^{[1
]}

Anantha R.V. ^{[1
,2
]}

Xu S.X. ^{[2
]}

Donnelly M. ^{[1
]}

Haeryfar S.M.M. ^{[2
]}

McCormick J.K. ^{[2
]}

Mele T. ^{[1
,2
,3
,4
]}

机构：

[1] Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, ON

[2] Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON

[3] Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON

[4] Division of General Surgery and Critical Care, London Health Sciences Centre, University Hospital, London, ON N6A 5A5

来源：

BMC Research Notes | / 7卷 / 1期

基金：

加拿大健康研究院;

关键词：

Animal model; Cytokine analysis; Infectious diseases; Peritonitis; Sepsis; Sepsis score; Septic shock;

D O I：

10.1186/1756-0500-7-233

中图分类号：

学科分类号：

摘要：

Background: The lack of a reliable scoring system that predicts the development of septic shock and death precludes comparison of disease and/or treatment outcomes in animal models of sepsis. We developed a murine sepsis score (MSS) that evaluates seven clinical variables, and sought to assess its validity and reliability in an experimental mouse model of polymicrobial sepsis. Methods. Stool collected from the cecum of C57BL/6 (B6) mice was dissolved in 0.9% normal saline (NS) and filtered, resulting in a fecal solution (FS) which was injected intraperitoneally into B6 mice. Disease severity was monitored by MSS during the experimental timeline. Blood and tissue samples were harvested for the evaluation of inflammatory changes after sepsis induction. The correlation between pro-inflammatory markers and MSS was assessed by the Spearman rank correlation coefficient. Results: Mice injected with FS at a concentration of 90 mg/mL developed polymicrobial sepsis with a 75% mortality rate at 24 hours. The MSS was highly predictive of sepsis progression and mortality, with excellent discriminatory power, high internal consistency (Cronbach alpha coefficient = 0.92), and excellent inter-rater reliability (intra-class coefficient = 0.96). An MSS of 3 had a specificity of 100% for predicting onset of septic shock and death within 24 hours. Hepatic dysfunction and systemic pro-inflammatory responses were confirmed by biochemical and cytokine analyses where the latter correlated well with the MSS. Significant bacterial dissemination was noted in multiple organs. Furthermore, the liver, spleen, and intestine demonstrated histopathological evidence of injury. Conclusions: The MSS reliably predicts disease progression and mortality in an animal model of polymicrobial sepsis. More importantly, it may be used to assess and compare outcomes among various experimental models of sepsis, and serve as an ethically acceptable alternative to death as an endpoint. © 2014 Shrum et al.; licensee BioMed Central Ltd.

引用

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