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.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Cell Biology