Blood flow resistance during hemodilution: Effect of plasma composition

Objectives: To investigate the causes of wide variations in reported effects of hemodilution on flow resistance of vascular beds. Methods: (a) In a meta-analysis of 28 prior studies, resistance values at hematocrits of zero (R⁰) and 0.45 (R_0.45) were derived. Study design characteristics (presence of vasodilatory reserve or leukocytes, species, tissue, hemodiluent) were tested by ANOVA for their relation to the ratio R₀/R_0.45. (b) Experiments were performed to determine flow resistance during hemodilution in the rat mesentery with (n = 8) and without (n = 11) pretreatment with heparinase, which modifies the endothelial glycocalyx. (c) A mathematical flow simulation for mesenteric microvascular networks was used to predict resistance effects of hemodilution and of a hypothetical layer on the endothelial surface. Results: (a) In prior studies using native plasma for hemodilution R₀ averaged 59 ± 8% of R_0.45, while in studies using artificial solutions R₀ averaged 32 ± 12% of R_0.45. The larger reduction of flow resistance upon dilution with artificial media is independent of viscosity and oncotic pressure. Other design characteristics did not show strong significant effects. (b) Present experiments showed large reductions of flow resistance with saline hemodilution which were nearly halved after heparinase pretreatment. (c) Resistance effects of hemodilution with plasma or after heparinase treatment agree with model predictions based on tube flow theology of blood. The larger resistance effects of dilution with artificial media can be explained by the removal of an endothelial surface layer of ~ 1.5 μm thickness. Conclusions: The results imply that changes of plasma composition, due to use of artificial infusion media, influence peripheral resistance and tissue perfusion. They are consistent with the hypothesis that interactions between endothelial glycocalyx structures and plasma components lead to formation of a thick layer at the endothelial surface which increases flow resistance.