Abstract
BackgroundThe 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.MethodsStool 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.ResultsMice 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.ConclusionsThe 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.
Highlights
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
In the fecal-induced peritonitis (FIP) model, a freshly prepared fecal solution is derived from murine colonic stool and injected intraperitoneally into mice at a defined concentration to result in acute peritonitis
We independently developed and validated a murine sepsis score (MSS) which evaluates seven individual criteria, and results in an aggregate score to evaluate the clinical condition of mice with experimental polymicrobial sepsis
Summary
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. Given that sophisticated scoring systems, such as the Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA) score, can evaluate the degree of critical illness and provide prognostic clarity for patients with sepsis [14], the development of similar metrics for animal models would allow for the consistent and standardized reporting of disease severity and therapeutic outcomes. We assessed the specificity and sensitivity of the MSS for predicting the onset of severe sepsis and death in a mouse model of FIP, and evaluated its reproducibility and reliability in corroborating with sepsis severity
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
