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Dynamic Multiorgan Dysfunction After Trauma With Secondary Sepsis in Rats: A 6-72-Hour Temporal Map Validated by
Baisheng Sun1, Dongxu Qian1,2, Cong Zhang3
1Department of Critical Care Medicine, the First Medical Centre, Chinese PLA General Hospital, Beijing, China.
Purpose:
This study aimed to quantify the temporal evolution of multiple 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 puncture 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 cells, interleukin (IL)-6, and 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 first onset, and pulmonary and renal dysfunction 24 hours after the first 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 first onset. Moreover, coagulation dysfunction started 12 hours after the first 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.
Insights
Trauma combined with sepsis significantly increases mortality and organ dysfunction, with cardiac and liver issues appearing earliest. A new scoring system helps track multi-organ dysfunction syndrome (MODS) progression in animal models.
Area of Science:
- Trauma and Surgical Infections
- Critical Care Medicine
- Animal Models of Disease
Background:
- Multi-organ dysfunction syndrome (MODS) is a critical complication following severe trauma and secondary sepsis.
- Understanding the temporal dynamics of MODS is crucial for timely therapeutic interventions.
- Existing scoring systems may not fully capture the complexity of MODS in preclinical models.
Purpose of the Study:
- To quantify the temporal evolution of multi-organ dysfunction syndrome (MODS) in a rodent model combining trauma and secondary sepsis.
- To validate a rodent-specific MODS scoring system for assessing organ dysfunction over a 6-72 hour period.
- To establish a quantitative profile of MODS development following combined injury.
Main Methods:
- 168 male Sprague-Dawley rats were divided into control, fracture, cecal ligation and perforation (CLP), and combined fracture+CLP groups.
- A stepwise CLP procedure was performed 24 hours after fracture surgery to simulate clinical conditions.
- Hematological parameters and histopathological tissue changes were analyzed at 6, 12, 24, 48, and 72 hours.
Main Results:
- The combined fracture+CLP group exhibited a significantly higher mortality rate (58.33%) compared to other groups.
- Elevated white blood cell (WBC), IL-6, and IL-10 levels peaked at 24 hours in the fracture+CLP group.
- Cardiac and hepatic dysfunction appeared at 12 hours, followed by pulmonary, renal, and neurological dysfunction at 24 hours in the fracture+CLP group.
Conclusions:
- A detailed 6-72 hour profile of MODS across six organ systems was established.
- Cardiac and hepatic dysfunction emerged earliest (12 hours), followed by pulmonary, renal, neurological, and coagulatory failure (24 hours).
- The validated MODS scoring system provides a translational tool for timing interventions in MODS research.
