Hydroxyethyl Starch, but Not Modified Fluid Gelatin, Affects Inflammatory Response in a Rat Model of Polymicrobial Sepsis with Capillary Leakage

In Brief BACKGROUND: Intravascular volume therapy is crucial in septic patients to improve tissue perfusion and maintain stable hemodynamics. Modified fluid gelatins (MFG) and medium weight hydroxyethyl starches (HES) are the most widely used synthetic colloids. Our aim in this study, performed in septic rats challenged by cecal ligation and puncture (CLP), was to investigate the effects of HES and MFG on pulmonary capillary leakage and to determine whether an antiinflammatory mechanism was involved. METHODS: Animals were randomly allocated to eight groups: saline control; CLP and saline; CLP and HES (7.5, 15, and 30 mL/kg); CLP and MFG (7.5, 15, and 30 mL/kg). Each group had 20 rats, 10 of which were used for pulmonary capillary leakage and 10 for other measurements. Four hours after CLP, the specified doses of HES or MFG were infused. Six hours after surgery, pulmonary capillary leakage, levels of tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2, intercellular adhesion molecule-1 mRNA expression, myeloperoxidase activity, lung histological changes, and nuclear factor-κB activation were measured. RESULTS: HES and MFG significantly attenuated the increase in capillary leakage in a dose-dependent manner. In addition, HES could decrease tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2 expression, intercellular adhesion molecule-1 mRNA expression, myeloperoxidase activity, neutrophil infiltration, and nuclear factor-κB activation, whereas MFG could not. CONCLUSIONS: HES may attenuate capillary leakage by modulating an inflammatory response, whereas an antiinflammatory mechanism was not involved in the effects of MFG on capillary leakage. IMPLICATIONS: Synthetic colloids are widely used to preserve normal intravascular volume in septic patients. There is debate, however, over which synthetic colloid to be used. In this rat model of sepsis induced by cecal ligation and puncture, hydroxyethyl starch inhibited inflammatory mediators and neutrophil infiltration, whereas modified fluid gelatin did not. Although the results cannot be directly extrapolated to the clinical setting, they encourage further research in patients.