title: PEG-albumin supraplasma expansion is due to increased vessel wall shear stress induced by blood viscosity shear thinning.
abstract: We studied the extreme hemodilution to a hematocrit of 11% induced by three plasma expanders: polyethylene glycol (PEG)-conjugated albumin (PEG-Alb), 6% 70-kDa dextran, and 6% 500-kDa dextran. The experimental component of our study relied on microelectrodes and cardiac output to measure both the rheological properties of plasma-expander blood mixtures and nitric oxide (NO) bioavailability in vessel walls. The modeling component consisted of an analysis of the distribution of wall shear stress (WSS) in the microvessels. Our experiments demonstrated that plasma expansion with PEG-Alb caused a state of supraperfusion with cardiac output 40% above baseline, significantly increased NO vessel wall bioavailability, and lowered peripheral vascular resistance. We attributed this behavior to the shear thinning nature of blood and PEG-Alb mixtures. To substantiate this hypothesis, we developed a mathematical model of non-Newtonian blood flow in a vessel. Our model used the Quemada rheological constitutive relationship to express blood viscosity in terms of both hematocrit and shear rate. The model revealed that the net effect of the hemodilution induced by relatively low-viscosity shear thinning PEG-Alb plasma expanders is to reduce overall blood viscosity and to increase the WSS, thus intensifying endothelial NO production. These changes act synergistically, significantly increasing cardiac output and perfusion due to lowered overall peripheral vascular resistance.
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California-San Diego, La Jolla, California 92093-0412, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Sriram
authors.forename: Amy G
authors.initials: AG
authors.lastname: Tsai
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.forename: Fantao
authors.initials: F
authors.lastname: Meng
authors.forename: Seetharama A
authors.initials: SA
authors.lastname: Acharya
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Tartakovsky
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001809:Blood Viscosity / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D003911:Dextrans / Q000494:pharmacology*; D006400:Hematocrit; D006438:Hemodilution; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D010952:Plasma Substitutes / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D033081:Shear Strength / Q000187:drug effects* / Q000502:physiology
chemical_list: D003911:Dextrans; D010952:Plasma Substitutes; D009569:Nitric Oxide; D011092:Polyethylene Glycols