title: Increased viscosity of hemoglobin-based oxygen carriers retards NO-binding when perfused through narrow gas-permeable tubes.
abstract: Increased fluid viscosity of a solution of hemoglobin-based oxygen carriers (HBOCs) reduces vasoconstrictive effects because increased shear stress on the vascular wall enhances the production of vasorelaxation factors such as NO. Nevertheless, on a microcirculatory level, it remains unclear how viscosity affects the reaction of HBOCs and NO. In this study, different HBOCs were perfused through narrow gas-permeable tubes (25 μm inner diameter at 1 mm/s centerline velocity; hemoglobin concentration [Hb]=5 g/dL). The reaction was examined microscopically based on the Hb visible-light absorption spectrum. When immersed in a NO atmosphere, the NO-binding of deoxygenated Hb solution (viscosity, 1.1 cP at 1000 s(-1)) in the tube occurred about twice as rapidly as that of red blood cells (RBCs): 1.6 cP. Binding was reduced by PEGylation (PEG-Hb, 7.7 cP), by addition of a high molecular weight hydroxyethyl starch (HES) (2.8 cP), and by encapsulation to form Hb-vesicles (HbVs, 1.5 cP; particle size 279 nm). However, the reduction was not as great as that shown for RBCs. A mixture of HbVs and HES (6.2 cP) showed almost identical NO-binding to that of RBCs. Higher viscosity and particle size might reduce lateral diffusion when particles are flowing. The HbVs with HES showed the slowest NO-binding. Furthermore, Hb encapsulation and PEGylation, but not HES-addition, tended to retard CO-binding. Increased viscosity reportedly enhances production of endothelium NO. In addition, our results show that the increased viscosity also inhibits the reaction with NO. Each effect might mitigate vasoconstriction.
authors.affiliation: Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, Japan. hirosakai@aoni.waseda.jp
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.forename: Naoto
authors.initials: N
authors.lastname: Okuda
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeoka
authors.forename: Eishun
authors.initials: E
authors.lastname: Tsuchida
mesh_terms: D001802:Blood Substitutes / Q000737:chemistry / Q000378:metabolism*; D002248:Carbon Monoxide / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D006454:Hemoglobins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry; D008081:Liposomes; D044085:Microfluidics; D009569:Nitric Oxide / Q000378:metabolism*; D010316:Particle Size; D010477:Perfusion; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013053:Spectrophotometry; D014783:Viscosity
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D008081:Liposomes; C109960:PEG-hemoglobin; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D002248:Carbon Monoxide; C100003:deoxyhemoglobin