Synergy between shear-induced migration and secondary flows on red blood cells transport in arteries: considerations on oxygen transport

Abstract

Shear-induced migration of red blood cells (RBCs) is a well-known phenomenon characterizing blood flow in the small vessels (micrometre to millimetre size) of the cardiovascular system. In large vessels, like the abdominal aorta and the carotid artery (millimetre to centimetre size), the extent of this migration and its interaction with secondary flows has not been fully elucidated. RBC migration exerts its influence primarily on platelet concentration, oxygen transport and oxygen availability at the luminal surface, which could influence vessel wall disease processes in and adjacent to the intima. Phillips' shear-induced particle migration model, coupled to the Quemada viscosity model, was employed to simulate the macroscopic behaviour of RBCs in four patient-specific geometries: a normal abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the near-wall region with a lowering of wall haematocrit (volume fraction of RBCs) on the posterior side of the normal aorta and on the lateralexternal side of the iliac arteries. A marked migration is observed on the outer wall of the carotid sinus, along the common carotid artery and in the carotid stenosis. No significant migration is observed in the AAA. The spatial and temporal patterns of wall haematocrit are correlated with the near-wall shear layer and with the secondary flows induced by the vessel curvature. In particular, secondary flows accentuate the initial lowering in RBC near-wall concentration by convecting RBCs from the inner curvature side to the outer curvature side. The results reinforce data in literature showing a decrease in oxygen partial pressure on the inner curvature wall of the carotid sinus induced by the presence of secondary flows. The lowering of wall haematocrit is postulated to induce a decrease in oxygen availability at the luminal surface through a diminished concentration of oxyhaemoglobin, hence contributing, with the reported lowered oxygen partial pressure, to local hypoxia.

Mechanical Activation of Hypoxia-Inducible Factor 1α Drives Endothelial Dysfunction at Atheroprone Sites

“…Our study also indicates that a functional interplay exists between EC mechanoresponses and hypoxia because exposure to low shear stress enhanced HIF1α activation in response to hypoxic signaling. Thus, EC at atheroprone sites are primed for responses to localized hypoxia, which may be caused by secondary flows that convect oxygen away from the arterial wall 37 or from consumption of oxygen by metabolically active macrophages. 38 …”

Zebrafish Model for Functional Screening of Flow-Responsive Genes

“…Computational modeling and empirical measurements suggest that this process can be influenced by secondary flows, which convect oxygen away from the vessel wall to generate regions with reduced oxygen levels. 45,46 By contrast, oxygenation of zebrafish embryos (up to 72 hpf) does not rely on circulation because diffusion is sufficient because of their small size. 22–24 Thus, although sites of disturbed flow in the aorta may have lower oxygen tensions leading to enhanced hypoxia-inducible factor 1α activation, this pathway is not activated in zebrafish in response to flow cessation because diffusion prevents the development of a hypoxic environment.…”

Mechanical Platelet Activation Potential in Abdominal Aortic Aneurysms

“…There is evidence that platelets congregate toward the walls of smaller blood vessels. In larger vessels, however, these effects are expected to be minimal [61] because the flow is complex and highly three-dimensional. In any case, the levels of AP in this study were orders of magnitude lower than the expected thresholds, and it is unlikely that the seeding distribution will affect this conclusion.…”