Am. J. Respir. Crit. Care Med., Vol 157, No. 1, Jan 1998, 129-134.
Leukocyte activation and flow behavior in rat skeletal muscle in sepsis [In Process Citation]
RD Piper, ML Pitt-Hyde, LA Anderson, WJ Sibbald and RF Potter
The London Health Sciences Centre, Department of Medicine, University of Western Ontario, Canada.
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.
