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Updated: Jun 23, 2026
A Reproducible Intensive Care Unit-Oriented Endotoxin Model in Rats
Published on: February 20, 2021
Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats
Satar Mortaza1, M Carmen Martinez, Céline Baron-Menguy
1Laboratoire HIFIH UPRES EA 3859 , Université d'Angers, Angers, France.
Objective:
Microparticles (MPs) are membrane vesicles with procoagulant and proinflammatory properties released during cell activation and might be potentially involved in the pathophysiology of septic shock. This study was designed to assess the effects of MPs from septic origin on the systemic hemodynamics as well as on the inflammatory, oxidative, and nitrosative stresses.
Design:
A prospective, randomized, controlled experimental study with repeated measurements.
Setting:
Investigational animal laboratory.
Subjects:
Forty healthy rats were randomly allocated to three groups: 10 animals inoculated with MPs isolated from control rats (cMPs), 15 animals inoculated with MPs isolated from sham rats (shMPs), and 15 animals inoculated with MPs isolated from rats with peritonitis (sMPs).
Interventions:
Rats were anesthetized, mechanically ventilated, and infused with the same amount of cMPs, shMPs, or sMPs. We measured the heart rate, mean arterial pressure, carotid artery, and portal vein blood flows. Hemodynamic parameters were recorded during 7 hours, and then animals were killed. Aorta and heart were harvested for further in vitro tissue analyses.
Measurements And Main Results:
1) The cellular origin (phenotype) but not the circulating concentration of MPs was different in septic rats, characterized by a significant increase in leukocyte-derived MPs. 2) sMPs but not cMPs or shMPs decreased mean arterial pressure without any effect on carotid artery and portal vein blood flows. 3) Rats inoculated with sMPs exhibited an increase in superoxide ion production and nuclear factor kappa B activity, overexpression of inducible nitric oxide synthase with subsequent nitric oxide overproduction and decrease in endothelial nitric oxide synthase activation.
Conclusions:
Rats with sepsis induced by peritonitis exhibited a specific phenotype of MPs. Inoculation of sMPs in healthy rats reproduced hemodynamic, septic inflammatory patterns, associated with oxidative and nitrosative stresses.
Insights
Microparticles (MPs) from septic rats, characterized by increased leukocyte-derived MPs, caused septic shock-like conditions in healthy rats. These septic microparticles (sMPs) induced hemodynamic changes and increased oxidative and nitrosative stress.
Area of Science:
- Cardiovascular Research
- Immunology
- Critical Care Medicine
Background:
- Microparticles (MPs) are vesicles released during cell activation with potential roles in septic shock.
- Septic shock involves complex pathophysiological mechanisms, including inflammation and oxidative stress.
Purpose of the Study:
- To investigate the effects of MPs from septic rats on systemic hemodynamics.
- To assess the impact of septic MPs on inflammatory, oxidative, and nitrosative stress markers.
Main Methods:
- A prospective, randomized, controlled experimental study in rats.
- Rats were inoculated with MPs from control, sham, or septic rats.
- Hemodynamic parameters and tissue analyses were performed over 7 hours.
Main Results:
- Septic rats showed a distinct MP phenotype, with increased leukocyte-derived MPs.
- Septic MPs (sMPs) decreased mean arterial pressure but did not affect blood flow in carotid or portal veins.
- sMPs increased superoxide production, NF-kappa B activity, and nitric oxide overproduction, while decreasing eNOS activation.
Conclusions:
- Sepsis induces a specific MP phenotype.
- Inoculation of sMPs in healthy rats replicated hemodynamic and inflammatory patterns of sepsis.
- sMPs contribute to oxidative and nitrosative stress in a sepsis model.
