Dose-dependent mortality and organ injury in a cecal slurry peritonitis model

Abstract

Background: The cecal slurry model was introduced as an alternative method for creating an animal sepsis model. This study was performed to evaluate dose-dependent mortality and organ injury in a sepsis model of cecal slurry peritonitis.

Materials and methods: Male Sprague-Dawley rats were divided into 5.0, 7.5, 10, or 15 mL/kg groups, according to the volume of cecal slurry administered into the peritoneal cavity. In the survival study, rats were observed for 14 d after sepsis induction. In the second experiment, blood and tissue were harvested to measure organ injury and the 2', 7'-dichlorofluorescein diacetate concentrations.

Results: All rats in the 5.0 mL/kg group survived for 14 d, whereas all rats in the 15 mL/kg group died within 24 h. The survival rates in the 7.5 mL/kg and 10 mL/kg groups were 60% and 30%, respectively. In the arterial blood gas analysis, lactate concentrations increased and HCO3^- decreased in a dose-dependent manner across the groups. Alanine aminotransferase and blood urea nitrogen concentrations increased as the dose of cecal slurry increased. 2', 7'-Dichlorofluorescein diacetate concentrations also increased in a dose-dependent manner.

Conclusions: The cecal slurry model of sepsis evaluated in this study demonstrates dose-dependent mortality, metabolic acidosis, liver and kidney injuries, and reactive oxygen species production, and it could be used for subsequent sepsis experiments, considering the severity of sepsis induced.

Keywords: Animal models; Dose-response relationship; Mortality; Multiple organ failure; Sepsis.