Increased viscosity of hemoglobin-based oxygen carriers retards NO-binding when perfused through narrow gas-permeable tubes

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 (25μm inner diameter at 1mm/s centerline velocity; hemoglobin concentration [Hb]=5g/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, 1.1cP at 1000s^-1) in the tube occurred about twice as rapidly as that of red blood cells (RBCs): 1.6cP. Binding was reduced by PEGylation (PEG-Hb, 7.7cP), by addition of a high molecular weight hydroxyethyl starch (HES) (2.8cP), and by encapsulation to form Hb-vesicles (HbVs, 1.5cP; particle size 279nm). However, the reduction was not as great as that shown for RBCs. A mixture of HbVs and HES (6.2cP) 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.