Dynamic Multi-organ Dysfunction After Trauma with Secondary Sepsis in Rats: A 6–72 hours Temporal Map Validated by Rodent-Specific MODS Scoring

Purpose: To quantify the temporal evolution of multi-organ dysfunction syndrome (MODS) following trauma with secondary sepsis and to validate a rodent-specific MODS scoring system over 6–72 hours. Methods: A total of 168 male Sprague-Dawley rats (8 weeks old, SPF grade) were randomly divided into four groups: the normal control group (NC group), limb crush injury group (Fx group), cecal ligation and perforation group (CLP group), and limb crush injury combined with CLP group (Fx+CLP group). A stepwise CLP surgery was performed in the Fx+CLP group 24 hours after closed tibial and fibular fracture surgery to mimic the clinical window of high infection incidence. Five observation time points were set: 6, 12, 24, 48, and 72 hours. Hematological parameters were detected and tissues of rats were examined histopathologically before a diagnostic scoring system for MODS in experimental animals was constructed. Results: The mortality rate of the Fx+CLP group was 58.33%, significantly higher than in the other groups (P<0.01). The levels of white blood cell (WBC), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the Fx+CLP group, which peaked at 24 hours, were notably higher than those of the CLP group at each time point (P<0.01). During the organ-function-assessment, the Fx+CLP group started to present with cardiac and hepatic dysfunction 12 hours after the 1st onset, and pulmonary and renal dysfunction 24 hours after the 1st onset. The pathological damage to the organs worsened with time. Particularly, the brain tissue pathology suggested that the pathological score of the Fx+CLP group exceeded 2 at 24 hours after the 1st onset. Moreover, coagulation dysfunction started 12 hours after the 1st onset. In general, the timing features of organ damage were distinct, and the overall damage was much more severe than in the single-factor damage groups. Conclusions: A consecutive 6-to-72-hour quantitative profile of MODS across six organ systems was established, demonstrating that cardiac and hepatic dysfunction emerged at 12 hours, followed by pulmonary, renal, neurological, and coagulatory failure at 24 hours. The validated MODS score was expected to offer a robust translational tool for timing therapeutic interventions.