Small volume hypertonic hydroxyethyl starch reduces acute microvascular dysfunction after closed soft-tissue trauma

Abstract

A major pathway of closed soft-tissue injury is failure of microvascular perfusion combined with a persistently enhanced inflammatory response. We therefore tested the hypothesis that hypertonic hydroxyethyl starch (HS/HES) effectively restores microcirculation and reduces leukocyte adherence after closed soft-tissue injury. We induced closed soft-tissue injury in the hindlimbs of 14 male isoflurane-anaesthetised rats. Seven traumatised animals received 7.5% sodium chloride-6% HS/HES and seven isovolaemic 0.9% saline (NS). Six non-injured animals did not receive any additional fluid and acted as a control group. The microcirculation of the extensor digitorum longus muscle (EDL) was quantitatively analysed two hours after trauma using intravital microscopy and laser Doppler flowmetry, i.e. erythrocyte flux. Oedema was assessed by the wet-to-dry-weight ratio of the EDL. In NS-treated animals closed soft-tissue injury resulted in massive reduction of functional capillary density (FCD) and a marked increase in microvascular permeability and leukocyte-endothelial cell interaction as compared with the control group. By contrast, HS/HES was effective in restoring the FCD to 94% of values found in the control group. In addition, leukocyte rolling decreased almost to control levels and leukocyte adherence was found to be reduced by ~50%. Erythrocyte flux in NS-treated animals decreased to 90 ± 8% (mean sem), whereas values in the HS/HES group significantly increased to 137 ± 3% compared with the baseline flux. Oedema in the HS/HES group (1.06 ± 0.02) was significantly decreased compared with the NS-group (1.12 ± 0.01). HS/HES effectively restores nutritive perfusion, decreases leukocyte adherence, improves endothelial integrity and attenuates oedema, thereby restricting tissue damage evolving secondary to closed soft-tissue injury. It appears to be an effective intervention, supporting nutritional blood flow by reducing trauma-induced microvascular dysfunction.