HES 130 kD, but not crystalloid volume support reduces leukocyte–endothelial cell interaction during endotoxemia

Background

Increased leukocyte/endothelial cell interaction and deterioration of capillary perfusion represent key mechanisms of septic organ dysfunction. Despite ongoing debate, however, the type of volume support to be used during septic disorders remains controversial. Using intravital microscopy we, therefore, studied microcirculatory effects of different clinically relevant volume therapy regimens, i.e. the synthetic colloid hydroxyethyl starch (HES, 160 kD) and a crystalloid regimen with isotonic saline solution (NaCl) in a new model of normotensive endotoxemia.

Methods

In Syrian hamsters, normotensive endotoxemia was induced by i.v. application of E. coli lipopolysaccharide (LPS, 2 mg/kg). The microcirculation was analysed in striated muscle of skinfold preparations. HES (Voluven^® 16 ml/kg, n = 7) or isotonic saline (NaCl, 66 ml/kg, n = 6) were infused 3 hours after LPS exposure over a 1-hour period (post-treatment mode). Animals, receiving LPS without volume therapy served as controls (n = 8, control). Leukocyte–endothelial cell interaction and functional capillary density (FCD, indicator of capillary perfusion quality) as well as macromolecular leakage were repeatedly analysed by intravital fluorescence microscopy in the awake animals during a 24 hour-period after LPS exposure.

Results

HES significantly attenuated LPS-induced arteriolar and venular leukocyte adherence (P < 0.05), whereas NaCl volume resuscitation had no effect when compared with non-treated controls. In parallel, the LPS-induced decrease in FCD and the increase in macromolecular leakage were significantly attenuated by HES, but not by NaCl.

Conclusions

Thus, our study indicates for the first time a protective effect on the microcirculation by HES volume resuscitation during endotoxemia, even when used in a clinically relevant post-treatment mode.