Volume 3 Supplement 1
Antithrombin III (AT III) prevents increased permeability and leukocyte adhesion in response to endotoxin (LPS) in the microcirculation of rat mesentery
© Current Science Ltd 1999
Published: 16 March 2000
Clinical trials with substitution of AT III in patients with sepsis showed a trend towards reduction of mortality and a positive effect on development and course of multiple organ failure. The mode of action is under discussion. Recent experimental studies suggest a possible effect on microvascular permeability and endothelial leukocyte adhesion.
By means of intravital microscopy we investigated the effect of substitution of AT III on LPS-induced microvascular leakage and leukocyte adhesion in the rat mesentery. Male CD rats (300-400 g bw) were used. The animals were infused with 0.5 mg/kg LPS (E. coli O55:B5) over 80 min. Vascular leakage was detected with FITC-marked rat serum albumin by fluorescence microscopy and evaluated by grey value analysis with a computer assisted image processing system. Light microscopy was used to evaluate the adherence of leukocytes to the vessel wall of postcapillary venules. Two treated groups received 500 U/kg AT III either 20 min prior (pretreatment) or 20 min after (posttreament) the beginning of LPS-infusion. Groups of animals not infused with LPS (sham), and infused with LPS ± placebo (albumin), served as controls. The observation period was 3 h after the beginning of LPS infusion.
Infusion of LPS led to a significant increase in microvascular permeability and leukocyte adherence compared to unstimulated controls. Both effects were reduced to the level of unstimulated controls by substitution of AT III. No significant differences were found between the pretreated or the posttreated group. Treatment with placebo and LPS showed no difference compared to the untreated LPS group.
Substitution of AT III, even when it is given after the inflammatory stimulus, ameliorates vascular leakage and leukocyte adhesion to the vessel wall as a consequence of LPS infusion. Thus, AT III could improve the microcirculation in the course of a generalised inflammatory reaction.