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Updated: Aug 24, 2026

Endotoxin Activity Assay for the Detection of Whole Blood Endotoxemia in Critically Ill Patients
Published on: June 24, 2019
Microhemodynamic and cellular mechanisms of activated protein C action during endotoxemia
Johannes N Hoffmann1, Brigitte Vollmar, Matthias W Laschke
1Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Objective:
To characterize microcirculatory actions of activated protein C in an endotoxemia rodent model that allows in vivo studies of microvascular inflammation and perfusion dysfunction.
Design:
Animal study using intravital microscopy.
Setting:
Animal research facility.
Subjects:
Male Syrian golden hamsters, 6-8 wks old with a body weight of 60-80 g.
Interventions:
In skinfold preparations, endotoxemia was induced by intravenous administration of 2 mg/kg endotoxin (lipopolysaccharide, Escherichia coli). Intravital microscopy allowed quantitative analysis of arteriolar and venular leukocyte adhesion and functional capillary density (cm) that served as a measure of microvascular perfusion failure. Activated protein C (APC group, n = 8, 24 microg/kg intravenously) was substituted continuously during 8 hrs after lipopolysaccharide, whereas endotoxemic buffer-treated animals (control, n = 7) served as controls.
Measurements And Main Results:
Lipopolysaccharide increased leukocyte adhesion and decreased functional capillary density to 50% of baseline values (p <.01 vs. baseline). Activated protein C treatment inhibited (p <.05) lipopolysaccharide-mediated leukocytic response and attenuated (p <.05) endotoxic perfusion failure in nutritive capillaries.
Conclusions:
Activated protein C-induced protection from lipopolysaccharide-mediated microcirculatory dysfunction was characterized in vivo for the first time. The impressive modification of leukocyte cross-talk indicates systemic anti-inflammatory activated protein C effects on leukocytes and the endothelium, subsequently improving capillary perfusion. These actions could represent the in vivo mechanism of activated protein C interactions observed in patients with severe sepsis.
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