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Impact of stochastic fluctuations in the cell free layer on nitric oxide bioavailability.

Park SW, Intaglietta M, Tartakovsky DM - Front Comput Neurosci (2015)

Bottom Line: We show that effects due to random boundaries do not average to zero and lead to an increase of NO bioavailability.The proposed stochastic formulation captures the natural continuous and microscopic variability, whose amplitude is measurable and is of the scale of cellular dimensions.It provides a realistic model of NO generation and regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, USA.

ABSTRACT
A plasma stratum (cell free layer or CFL) generated by flowing blood interposed between the red blood cell (RBC) core and the endothelium affects generation, consumption, and transport of nitric oxide (NO) in the microcirculation. CFL width is a principal factor modulating NO diffusion and vessel wall shears stress development, thus significantly affecting NO bioavailability. Since the CFL is bounded by the surface formed by the chaotically moving RBCs and the stationary but spatially non-uniform endothelial surface, its width fluctuates randomly in time and space. We analyze how these stochastic fluctuations affect NO transport in the CFL and NO bioavailability. We show that effects due to random boundaries do not average to zero and lead to an increase of NO bioavailability. Since endothelial production of NO is significantly enhanced by temporal variability of wall shear stress, we posit that stochastic shear stress stimulation of the endothelium yields the baseline continual production of NO by the endothelium. The proposed stochastic formulation captures the natural continuous and microscopic variability, whose amplitude is measurable and is of the scale of cellular dimensions. It provides a realistic model of NO generation and regulation.

No MeSH data available.


Related in: MedlinePlus

Auto-correlation of the temporally fluctuating CFL width w reported by Ong et al. (2011a) (solid line) and the fitted exponential correlation function ρ(Δt) = exp(−Δt∕lt) with the correlation length lt = 0.007 s (dashed line).
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Figure 2: Auto-correlation of the temporally fluctuating CFL width w reported by Ong et al. (2011a) (solid line) and the fitted exponential correlation function ρ(Δt) = exp(−Δt∕lt) with the correlation length lt = 0.007 s (dashed line).

Mentions: The CFL width measurements (Ong et al., 2011a) are used to construct a probabilistic model for the random input parameter w(θ, t; ω) = r2 − r1 in which the random RBC-CFL interface r1(θ, t; ω) is given by Equation (11). These data, which represent temporal fluctuations of w at a single spatial location (say, θ = 0), give rise to the histogram and auto-correlation reported in Figures 1 and 2, respectively. This histogram (and the obvious fact that the CFL width is both non-negative and smaller than the vessel radius r2) indicates that the random field w(θ, t; ω) is non-Gaussian. We fit the histogram in Figure 1 with a beta distribution , where B(α, β) = Γ(α + β)∕[Γ(α)Γ(β)] is the beta function, Γ(·) is the complete gamma function, 0 ≤ W ≤ r2, and α > 0 and β > 0 are shape parameters. Setting α = 4.358 and β = 32.9 provides the best data fit, resulting in the mean CFL width μm. The auto-correlation data in Figure 2 were fitted with an exponential correlation function , yielding the correlation length lt = 0.007 s.


Impact of stochastic fluctuations in the cell free layer on nitric oxide bioavailability.

Park SW, Intaglietta M, Tartakovsky DM - Front Comput Neurosci (2015)

Auto-correlation of the temporally fluctuating CFL width w reported by Ong et al. (2011a) (solid line) and the fitted exponential correlation function ρ(Δt) = exp(−Δt∕lt) with the correlation length lt = 0.007 s (dashed line).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4621848&req=5

Figure 2: Auto-correlation of the temporally fluctuating CFL width w reported by Ong et al. (2011a) (solid line) and the fitted exponential correlation function ρ(Δt) = exp(−Δt∕lt) with the correlation length lt = 0.007 s (dashed line).
Mentions: The CFL width measurements (Ong et al., 2011a) are used to construct a probabilistic model for the random input parameter w(θ, t; ω) = r2 − r1 in which the random RBC-CFL interface r1(θ, t; ω) is given by Equation (11). These data, which represent temporal fluctuations of w at a single spatial location (say, θ = 0), give rise to the histogram and auto-correlation reported in Figures 1 and 2, respectively. This histogram (and the obvious fact that the CFL width is both non-negative and smaller than the vessel radius r2) indicates that the random field w(θ, t; ω) is non-Gaussian. We fit the histogram in Figure 1 with a beta distribution , where B(α, β) = Γ(α + β)∕[Γ(α)Γ(β)] is the beta function, Γ(·) is the complete gamma function, 0 ≤ W ≤ r2, and α > 0 and β > 0 are shape parameters. Setting α = 4.358 and β = 32.9 provides the best data fit, resulting in the mean CFL width μm. The auto-correlation data in Figure 2 were fitted with an exponential correlation function , yielding the correlation length lt = 0.007 s.

Bottom Line: We show that effects due to random boundaries do not average to zero and lead to an increase of NO bioavailability.The proposed stochastic formulation captures the natural continuous and microscopic variability, whose amplitude is measurable and is of the scale of cellular dimensions.It provides a realistic model of NO generation and regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, USA.

ABSTRACT
A plasma stratum (cell free layer or CFL) generated by flowing blood interposed between the red blood cell (RBC) core and the endothelium affects generation, consumption, and transport of nitric oxide (NO) in the microcirculation. CFL width is a principal factor modulating NO diffusion and vessel wall shears stress development, thus significantly affecting NO bioavailability. Since the CFL is bounded by the surface formed by the chaotically moving RBCs and the stationary but spatially non-uniform endothelial surface, its width fluctuates randomly in time and space. We analyze how these stochastic fluctuations affect NO transport in the CFL and NO bioavailability. We show that effects due to random boundaries do not average to zero and lead to an increase of NO bioavailability. Since endothelial production of NO is significantly enhanced by temporal variability of wall shear stress, we posit that stochastic shear stress stimulation of the endothelium yields the baseline continual production of NO by the endothelium. The proposed stochastic formulation captures the natural continuous and microscopic variability, whose amplitude is measurable and is of the scale of cellular dimensions. It provides a realistic model of NO generation and regulation.

No MeSH data available.


Related in: MedlinePlus