Impact of the Fåhraeus Effect on NO and O₂ Biotransport: A Computer Model

Abstract

Nitric oxide (NO) and oxygen (O2) transport in the microcirculation are coupled in a complex manner, since enzymatic production of NO depends on O2 availability, NO modulates vascular tone and O2 delivery, and tissue O2 consumption is reversibly inhibited by NO. The authors investigated whether NO bioavailability is influenced by the well-known Fåhraeus effect, which has been observed for over 70 years. This phenomenon occurs in small-diameter blood vessels, where the tube hematocrit is reduced below systemic hematocrit as a plasma boundary layer forms near the vascular wall when flowing red blood cells (rbcs) migrate toward the center of the bloodstream. Since hemoglobin in the bloodstream is thought to be the primary scavenger of NO in vivo, this might have a significant impact on NO transport. To investigate this possibility, the authors developed a multilayered mathematical model for mass transport in arterioles using finite element numerical methods to simulate coupled NO and O2 transport in the blood vessel lumen, plasma layer, endothelium, vascular wall, and surrounding tissue. The Fåhraeus effect was modeled by varying plasma layer thickness while increasing core hematocrit based on conservation of mass. Key findings from this study are that (1) despite an increase in the NO scavenging rate in the core with higher hematocrit, the model predicts enhanced vascular wall and tissue NO bioavailability due to the relatively greater resistance for NO diffusion through the plasma layer; (2) increasing the plasma layer thickness also increases the resistance for O2 diffusion, causing a larger P(O2) gradient near the vascular wall and decreasing tissue O2 availability, although this can be partially offset with inhibition of O2 consumption by higher tissue NO levels; (3) the Fåhraeus effect can become very significant in smaller blood vessels (diameters <30 microm); and (4) models that ignore the Fåhraeus effect may underestimate NO concentrations in blood and tissue.

Precise measurement of renal filtration and vascular parameters using a two-compartment model for dynamic contrast-enhanced MRI of the kidney gives realistic normal values

“…Mean K trans values for small cortical ROIs vary, then decrease progressively for ROIs larger than the cortex Table 1 and symbols in Table 5 MRT 0 mean residence time a From peak and MRT of delayed exponential or Gaussian VIRF; units: ml blood min −1 (100 ml [31], 31% (human brain) [32], 25% [33] and 8-20% [34] have been reported. This is related to the Fahraeus effect; in small vessels red blood cells travel faster than plasma [34,35]. The renal vasa recta (10-20 μm in diameter) have a reduced haematocrit of 40-50% compared with a large vessel [36]; the network Fahraeus effect can further reduce this by as much as 20% [34].…”

Nitric Oxide Scavenging by Red Blood Cells as a Function of Hematocrit and Oxygenation

“…It has long been known that the Hct of smaller vessels is less than that of larger vessels (47,48). This phenomenon, known as the Fåhraeus effect, is due to migration of red blood cells into the center of the vessels creating a cell-free zone near the endothelium layer, which results in a lower tube Hct (fractional volume of red cells in the vessel, including the cell-free zone) (47). The effect has been verified both experimentally and theoretically (47,48).…”

“…This phenomenon, known as the Fåhraeus effect, is due to migration of red blood cells into the center of the vessels creating a cell-free zone near the endothelium layer, which results in a lower tube Hct (fractional volume of red cells in the vessel, including the cell-free zone) (47). The effect has been verified both experimentally and theoretically (47,48). The Hct dependence of NO scavenging we report here is likely to play a role in how NO is scavenged in different vessels in normal physiology.…”

The potential of Angeli's salt to decrease nitric oxide scavenging by plasma hemoglobin

“…Three mechanisms contribute to reduced NO scavenging by RBCs [46]. : (1) the rate of the reaction is largely limited by external diffusion of NO through the plasma to the surface of the RBC [44], especially due to the presence of a red cell free zone adjacent to the vessel walls where NO is made [37][38][39]; (2) NO diffusion is partially blocked by a physical barrier across the RBC membrane [40,43,47]; and (3) RBC-encapsulated Hb is efficiently compartmentalized in the lumen; it does not extravasate into the endothelium and interstitium [44,[48][49][50][51][52].…”