title: Experimental Study on the Efficacy of Site-Specific PEGylated Human Serum Albumins in Resuscitation From Hemorrhagic Shock.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Male Wistar rats.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Linear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent.
authors.affiliation: 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.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Song
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cheng
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Lian
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D055370:Lung Injury / Q000517:prevention & control; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control; D012151:Resuscitation / Q000379:methods*; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D012709:Serum Albumin; D051028:bcl-2-Associated X Protein; D011092:Polyethylene Glycols; D052250:Nitric Oxide Synthase Type III