Antioxidative Resuscitation Solution Prevents Leukocyte Adhesion in the Liver after Hemorrhagic Shock

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Abstract
The generation of iron-dependent toxic oxygen radicals during the initial resuscitation from hemorrhagic shock was shown to be a relevant factor for the initiation of the inflammatory cascade. Therefore, this experimental study was designed to evaluate the effects of a deferoxamine-conjugated hydroxyethyl-starch solution (HES-DFO) on oxygen radical induced injury and microcirculatory alterations in the rat liver compared with resuscitation with regular hydroxyethyl-starch, lactated Ringer's solution (RL), or a gelatin-based solution. After hemorrhage and random assignment to 1 hour of blood-free resuscitation with the aforementioned solutions, hepatic microcirculation and leukocyte adhesion characteristics were assessed by intravital fluorescence microscopy in anesthetized rats. Oxygen radical activity was estimated by determination of glutathione levels in liver homogenate and determination of thiobarbituric acid-reactive substances in plasma as markers of lipid peroxidation. Resuscitation by HES-DFO resulted in restoration of hemodynamic parameters compared with gelatin-based solution and HES. The hepatic microcirculation was severely altered 1 hour after resuscitation from shock in all groups indicated by sinusoidal narrowing and reduced sinusoidal blood flow. HES-DFO, however, attenuated leukocyte adhesion and improved velocity index in sinusoids as well as sinusoidal perfusion. The shock-associated generation of oxygen radicals during resuscitation was prevented by HES-DFO as indicated by restored glutathione and reduced thiobarbituric acid-reactive substances. The results suggest that HES-DFO effectively reduces oxygen radical formation during the initial resuscitation period, thus, attenuating pathologically enhanced leukocyte adhesion and improving hepatic microcirculation.