• Xinlei Song, Shu Zhang, Yanna Cheng, Ting Zhao, Qianqian Lian, Lu Lu, and Fengshan Wang.
• 1Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan, China.2Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
• Crit. Care Med. 2016 Nov 1; 44 (11): e1090-e1096.

ObjectivesTo evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model.SettingLaboratory.SubjectsMale Wistar rats.DesignProspective study.InterventionsRats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids.Measurements And Main ResultsThe mean arterial pressure and blood gas variables were measured. Hemorheology analysis was performed to evaluate the influence of resuscitation on RBCs and blood viscosity. The microvascular state was indirectly characterized in terms of monocyte chemotactic protein-1 and endothelial nitric oxide synthase that related to shear stress and vasodilation, respectively. The levels of inflammation-related factors and apoptosis-related proteins were used to evaluate the reperfusion injury in lungs. The results showed that PEGylated human serum albumin could improve the level of mean arterial pressure and blood gas variables more effectively at the end of resuscitation. poly(ethylene glycol) modification was able to increase the viscosity of human serum albumin to the level of effectively enhancing the expression of monocyte chemotactic protein-1 and endothelial nitric oxide synthase, which could promote microvascular perfusion. The hyperosmotic resuscitative agents including both 25% human serum albumin and PEGylated human serum albumins could greatly attenuate lung injury. No significant therapeutic advantages but some disadvantages were found for Y shaped poly(ethylene glycol) modification over linear poly(ethylene glycol) modification, such as causing the decrease of erythrocyte deformability.ConclusionsLinear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent.

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