Related Experiment Videos
Leukocyte activation and flow behavior in rat skeletal muscle in sepsis
R D Piper1, M L Pitt-Hyde, L A Anderson
1The London Health Sciences Centre, Department of Medicine, University of Western Ontario, Canada.
Abstract:
In animal models of endotoxemia, sepsis is associated with the accumulation of leukocytes and altered microvascular perfusion. In order to test the hypothesis that bacterial sepsis upregulates leukocyte-endothelial adhesion, we used intravital microscopy to examine the flow behavior of leukocytes in the postcapillary venules (PCV) of rats made septic by cecal ligation and perforation (CLP). Animals were randomized to CLP or sham study groups and studied 6 h, 24 h, or 48 h later. In postcapillary venules of the extensor digitorum longus muscle, we found that: (1) over the course of the study, leukocyte adhesion and extravasation increased in both experimental groups (analysis of variance [ANOVA], significant time effect: adhesion, p < 0.001; extravasation, p < 0.05); (2) leukocyte adhesion was decreased by CLP treatment (ANOVA, sepsis effect, p = 0.05), particularly after 24 to 48 h of sepsis (ANOVA, sepsis x time interaction, p < 0.05); and (3) the reduction in leukocyte adhesion in CLP animals was associated with a decrease in leukocyte extravasation (ANOVA, sepsis effect, p < 0.01). After correction for the reduction in systemic leukocyte count associated with CLP, the effect of sepsis on leukocyte adhesion and extravasation no longer reached statistical significance. These findings suggest that chronic (6 to 48 h) bacterial sepsis does not upregulate leukocyte adhesion in a manner similar to that seen in models of acute endotoxemia. These data suggest that the increased microcirculatory flow heterogeneity seen in this and other models of bacterial sepsis may not be explained by leukocyte entrapment in postcapillary venules.
Insights
Bacterial sepsis in rats did not increase leukocyte adhesion to blood vessels, contrary to expectations. This suggests leukocyte entrapment in postcapillary venules doesn't explain sepsis-related blood flow issues.
Area of Science:
- Immunology
- Microcirculation
- Sepsis Pathophysiology
Background:
- Sepsis is linked to leukocyte accumulation and altered microvascular perfusion in animal models.
- Bacterial sepsis is hypothesized to increase leukocyte-endothelial adhesion.
Purpose of the Study:
- To investigate the effect of bacterial sepsis on leukocyte-endothelial adhesion and extravasation in rat postcapillary venules.
- To determine if sepsis upregulates leukocyte adhesion, potentially explaining microcirculatory dysfunction.
Main Methods:
- Intravital microscopy was used to observe leukocyte behavior in postcapillary venules of rats subjected to cecal ligation and perforation (CLP) or sham procedures.
- Animals were studied at 6, 24, and 48 hours post-procedure.
Main Results:
- Leukocyte adhesion and extravasation increased over time in both CLP and sham groups.
- CLP treatment decreased leukocyte adhesion, particularly at 24-48 hours, and was associated with reduced extravasation.
- After adjusting for reduced systemic leukocyte counts in CLP animals, the sepsis effect on adhesion and extravasation was not statistically significant.
Conclusions:
- Chronic bacterial sepsis (6-48 hours) in this rat model does not appear to upregulate leukocyte adhesion.
- The observed microcirculatory flow heterogeneity in sepsis may not be due to leukocyte entrapment in postcapillary venules.