The Effect of Small Changes in Hematocrit on Nitric Oxide Transport in Arterioles

Abstract

We report the development of a mathematical model that quantifies the effects of small changes in systemic hematocrit (Hct) on the transport of nitric oxide (NO) in the microcirculation. The model consists of coupled transport equations for NO and oxygen (O2) and accounts for both shear-induced NO production by the endothelium and the effect of changing systemic Hct on the rate of NO production and the rate of NO scavenging by red blood cells. To incorporate the dependence of the plasma layer width on changes in Hct, the model couples the hemodynamics of blood in arterioles with NO and O2 transport in the plasma layer. A sensitivity analysis was conducted to determine the effects of uncertain model parameters (the thicknesses of endothelial surface layers and diffusion coefficients of NO and O2 in muscle tissues and vascular walls) on the model's predictions. Our analysis reveals that small increases in Hct may raise NO availability in the vascular wall. This finding sheds new light on the experimental data that show that the blood circulation responds to systematic increases of Hct in a manner that is consistent with increasing NO production followed by a plateau.

Nitric oxide transport in an axisymmetric stenosis

“…Owing to the high NO reaction rate by RBCs, the presence of RBCs in the lumen significantly reduced the NO concentration on the endothelium, which has also been demonstrated in the capillaries and arterioles [16,21,37]. However, the effect of RBCs on NO transport in the artery was diminished by the existence of the RBC-free plasma layer at the blood-endothelium interface because of the much lower NO reaction rate in the layer, which was consistent with Liao et al's experiments [36].…”

Two-dimensional transient model for prediction of arteriolar NO/O2 modulation by spatiotemporal variations in cell-free layer width

“…1A) to account for the time-dependent changes in H C . In the present study, a step function (H C in BL) was used to describe the core hematocrit distribution in the arteriole (Ong et al, 2011b;Sriram et al, 2011). The NO scavenging rate in BL was reported to follow a linear relationship with H C (Lamkin-Kennard et al, 2004b):…”

“…where a, b and c are constants and μ c is the viscosity of the RBC core which varies linearly with H C (Sriram et al, 2011). The detailed derivation for the velocity profile and WSS is described in the Supplementary Material.…”

“…There have been a number of theoretical studies (Chen et al, 2006;Kavdia and Popel, 2003;Lamkin-Kennard et al, 2004b;Sriram et al, 2011) that proposed computational models to predict the bioavailability of NO at steady state, with the assumption of a uniform and axisymmetric CFL along the arteriole vessel. However, experimental studies (Alonso et al, 1993;Kim et al, 2007) have shown that RBCs are exposed to hemodynamic interactions resulting in their protrusions into the CFL and leading to dynamic changes in the CFL width.…”

Examining and Mitigating Acellular Hemoglobin Vasoactivity

“…Blood losses lower blood viscosity, thus increasing blood flow velocity; however, this effect is not able to preserve WSS due to the two-phase nature of blood (RBCs and plasma). When blood flows, an erythrocyte cellfree layer (CFL) is interposed between the RBC blood column and the vessel wall (97,140). This hydrodynamic layer is generated by the axial migration, resulting from the flexibility of red cells that causes them to migrate toward the center of the flow stream (117,134,135,163).…”