Impact of the Fåhraeus Effect on NO and O 2 Biotransport: A Computer Model

Nitric oxide (NO) and oxygen (O 2 ) transport in the microcirculation are coupled in a complex manner, since enzymatic production of NO depends on O 2 availability, NO modulates vascular tone and O 2 delivery, and tissue O 2 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 O 2 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 O 2 diffusion, causing a larger P O2 gradient near the vascular wall and decreasing tissue O 2 availability, although this can be partially offset with inhibition of O 2 consumption by higher tissue NO levels; (3) the Fåhraeus effect can become very significant in smaller blood vessels (diameters < 30 μm); and (4) models that ignore the Fåhraeus effect may underestimate NO concentrations in blood and tissue.