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

Despite the significant roles of the cell-free layer (CFL) in balancing nitric oxide (NO) and oxygen (O2) bioavailability in arteriolar tissue, many previous numerical approaches have relied on a one-dimensional (1-D) steady-state model for simplicity. However, these models are unable to demonstrate the influence of spatiotemporal variations in the CFL on the NO/O2 transport under dynamic flow conditions. Therefore, the present study proposes a new two-dimensional (2-D) transient model capable of predicting NO/O2 transport modulated by the spatiotemporal variations in the CFL width. Our model predicted that NO bioavailability was inversely related to the CFL width as expected. The enhancement of NO production by greater wall shear stress with a thinner CFL could dominate the diffusion barrier role of the CFL. In addition, NO/O2 availability along the vascular wall was inhomogeneous and highly regulated by dynamic changes of local CFL width variation. The spatial variations of CFL widths on opposite sides of the arteriole exhibited a significant inverse relation. This asymmetric formation of CFL resulted in a significantly imbalanced NO/O2 bioavailability on opposite sides of the arteriole. The novel integrative methodology presented here substantially highlighted the significance of spatiotemporal variations of the CFL in regulating the bioavailability of NO/O2, and provided further insight about the opposing effects of the CFL on arteriolar NO production.