Coupling of nitric oxide transport and blood flow: a computational modeling approach

Xuewen Chen

doi:10.17918/etd-1520

To date, the mechanisms by which Nitric Oxide (NO) is transported and its interactions with components in blood and tissue have not been fully elucidated. In this study, four computational models were developed to advance the understanding of the interacting mechanisms between NO, oxygen (O2) and hemodynamics in the microcirculation. The models were developed in increasingly complex phases, entailing the following steps: simulation of individual vessels, simulation of paired arteriole-venule, and simulation of small vessel networks in 3D configurations. To evaluate the effects of blood velocity profiles, red blood cell-free plasma layers and glycocalyx on coupled O2 and NO transport within and around small arterioles (30 [mu]m lumen diameter), a single vessel model was developed. Three blood velocity profiles (blunted, parabolic and plug) were tested in the model. The thicknesses of the plasma and glycocalyx layer were varied. The results indicate that most of the resistance to O2 transport is in the bloodstream, and is not due to high O2 consumption rates by the endothelium or the vascular wall, although the endothelium may be consuming significant amounts of O2 to produce NO. O2 transport to the surrounding vascular wall and tissue and axial PO2 gradients depend strongly on convection, whereas NO transport is dominated by diffusion and reaction with hemoglobin. Convective transport caused only minor variations in radial and axial NO gradients, which were primarily influenced by available O2 for endothelial NO production. The single vessel model was extended to study the effect of the presence of red blood cells (RBCs) in the plasma layer. The average hematocrit in the bloodstream was assumed to be constant in the central core and decreasing to zero in the boundary layer next to the endothelial surface layer (ESL). The effect of the presence or absence of RBCs near the endothelium was studied while varying the ESL and boundary layer thickness. With RBCs present in the boundary layer, the model predicts that there is a very small increase in PO2, but a significant decrease in NO in the endothelium and vascular wall. Scavenging of NO by hemoglobin decreases with the increase of the boundary layer thickness. The presence of RBCs in the plasma layer has a much larger effect on NO than on O2 transport. To evaluate the effect of capillaries on NO and O2 transport around an arteriole-venule pair, a vessel pair model was developed. Blood flow was assumed to be steady in the arteriolar and venular lumens and to obey Darcy's law in the tissue. Average NO consumption rate by capillary blood in a unit tissue volume was assumed proportional to the blood flux across the volume. The results predict that the capillary bed, which connects the arteriole and venule, facilitates the release of O2 from the vessel pair to the surrounding tissue. Increase in NO production from the venular wall may elevate NO concentration in the arteriolar wall if the venule is in proximity to the paired arteriole. The capillary bed between the paired arteriole and venule has also been shown to contribute to the maintenance of tissue NO level in the physiologically functioning range. To investigate the effect of shear stress related NO production and blood phase separation effect, a 3D blood vessel network model was developed to simulate NO transport in a piece of rat skeletal muscle. The NO production rate by the endothelium was assumed to linearly increase with shear stress. Hematocrit in each vessel was determined by blood phase separation effect. The model predicts that there are low wall shear stress regions in the outer walls at vessel bifurcation. These regions are associated with diminished NO production. The shear related NO production rate might be higher in the wall of the vessel branch that draws more blood from the parent vessel; however, the phase separation effect might decrease the NO contents in the wall of the vessel branch. In conclusion, this study provides useful tools to improve the fundamental understanding of the relationships between NO, O2, blood flow and the etiology of pathophysiological conditions.

Coupling of nitric oxide transport and blood flow: a computational modeling approach

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Coupling of nitric oxide transport and blood flow: a computational modeling approach

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