title: Small-volume resuscitation from hemorrhagic shock with polymerized human serum albumin.
abstract: Human serum albumin (HSA) is used as a plasma expander; however, albumin is readily eliminated from the intravascular space. The objective of this study was to establish the effects of various-sized polymerized HSAs (PolyHSAs) during small-volume resuscitation from hemorrhagic shock on systemic parameters, microvascular hemodynamics, and functional capillary density in the hamster window chamber model. Polymerized HSA size was controlled by varying the cross-link density (ie, molar ratio of glutaraldehyde to HSA). Hemorrhage was induced by controlled arterial bleeding of 50% of the animal's blood volume (BV), and hypovolemic shock was maintained for 1 hour. Resuscitation was implemented in 2 phases, first, by infusion of 3.5% of the BV of hypertonic saline (7.5% NaCl) then followed by infusion of 10% of the BV of each PolyHSA. Resuscitation provided rapid recovery of blood pressure, blood gas parameters, and microvascular perfusion. Polymerized HSA at a glutaraldehyde-to-HSA molar ratio of 60:1 (PolyHSA(60:1)) provided superior recovery of blood pressure, microvascular blood flow, and functional capillary density, and acid-base balance, with sustained volume expansion in relation to the volume infused. The high molecular weight of PolyHSA(60:1) increased the hydrodynamic radius and solution viscosity. Pharmacokinetic analysis of PolyHSA(60:1) indicates reduced clearance and increased circulatory half-life compared with monomeric HSA and other PolyHSA formulations. In conclusion, HSA molecular size and solution viscosity affect central hemodynamics, microvascular blood flow, volume expansion, and circulation persistence during small-volume resuscitation from hemorrhagic shock. In addition, PolyHSA can be an alternative to HSA in pathophysiological situations with compromised vascular permeability.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Munich (LMU), Campus Grosshadern, Munich 81377, Germany.
authors.forename: Catalina
authors.initials: C
authors.lastname: Messmer
authors.forename: Ozlem
authors.initials: O
authors.lastname: Yalcin
authors.forename: Andre F
authors.initials: AF
authors.lastname: Palmer
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006224:Cricetinae; D006339:Heart Rate; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008647:Mesocricetus; D012151:Resuscitation / Q000379:methods*; D012709:Serum Albumin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000075462:Serum Albumin, Human; D012771:Shock, Hemorrhagic / Q000628:therapy*; D014783:Viscosity
chemical_list: D012709:Serum Albumin; C032137:polyalbumin; D000075462:Serum Albumin, Human
references.citation: Resuscitation. 2008 Jun;77(3):379-86
references.pmid: 18308459
references.citation: Artif Cells Blood Substit Immobil Biotechnol. 2007;35(2):173-90
references.pmid: 17453703
references.citation: Am J Physiol. 1999 May;276(5):H1801-6
references.pmid: 10330266
references.citation: Crit Care Clin. 1992 Apr;8(2):341-53
references.pmid: 1568144
references.citation: Microvasc Res. 1973 May;5(3):309-12
references.pmid: 4709728
references.citation: J Trauma. 2011 Oct;71(4):798-807
references.pmid: 21336190
references.citation: Am J Physiol. 1984 Apr;246(4 Pt 2):H508-17
references.pmid: 6720909
references.citation: Ann R Coll Surg Engl. 2009 Nov;91(8):703-7
references.pmid: 19909614
references.citation: Microvasc Res. 1975 Sep;10(2):165-79
references.pmid: 1186524
references.citation: Biotechnol Prog. 2011 Jan-Feb;27(1):290-6
references.pmid: 21312376
references.citation: Biol Pharm Bull. 2002 Jun;25(6):695-704
references.pmid: 12081132
references.citation: Hosp Pract (1995). 2009 Dec;37(1):107-12
references.pmid: 20877178
references.citation: Shock. 2009 Mar;31(3):300-7
references.pmid: 18636045
references.citation: Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H363-73
references.pmid: 14975932
references.citation: Anesthesiology. 2009 Jul;111(1):187-202
references.pmid: 19512862
references.citation: Kidney Int Suppl. 1998 Sep;67:S100-8
references.pmid: 9736263
references.citation: N Engl J Med. 2004 May 27;350(22):2247-56
references.pmid: 15163774
references.citation: Microvasc Res. 1978 Jan;15(1):93-101
references.pmid: 634160
references.citation: Biochem J. 1973 Dec;135(4):867-73
references.pmid: 4204954
references.citation: Protein Eng. 1999 Jun;12(6):439-46
references.pmid: 10388840
references.citation: Am Heart J. 2004 Jan;147(1):91-9
references.pmid: 14691425
references.citation: J Pharm Sci. 1996 Apr;85(4):393-5
references.pmid: 8901075
references.citation: Farmaco. 1999 Oct 30;54(10):695-9
references.pmid: 10575739
references.citation: Shock. 2007 Apr;27(4):380-9
references.pmid: 17414420
references.citation: Ann Surg. 2011 Mar;253(3):470-83
references.pmid: 21217516
references.citation: Mil Med. 1984 Feb;149(2):55-62
references.pmid: 6427656
references.citation: Intensive Care Med. 1989;15(2):116-20
references.pmid: 2715499
references.citation: Crit Care. 2000;4(3):151-5
references.pmid: 11211856
references.citation: Res Exp Med (Berl). 1980;177(2):125-34
references.pmid: 7003665
references.citation: Transfus Apher Sci. 2002 Aug;27(1):59-72
references.pmid: 12201472