Numerical Analysis Of NO Transport Characteristics And Its Application In Diabetic Microcirculation Evaluation

Microvascular disease is one of the serious complications of diabetes mellitus,which significantly affect the life of diabetic patients.The imbalance of the vasoactive substance secreted by vascular endothelial cell is the major factor inducing microvascular complications.As the most important endothelium-derived relaxing factor,NO is involved in lots of physiological actions of microcirculation and plays an important role in vasodilation.NO transport is closely associated with hemorheology,hemodynamics and microvascular structure.Its essence is a multiphysics coupling problem,involving various processes of flow,diffusion,and reactions which can be observed in the discipline of engineering thermo-physics as well.The purpose of this study is to explore the effect of microvascular functional and structural alterations on NO transport through numerical analysis and investigate the clinical implications for early assessment of microcirculation dysfunction of diabetic mellitus.The main contents are described as follows:Finite element analysis of Stokes/Darcy fluid flow and NO transport in system of permeable capillary and tissue has been employed to simulate NO transport in capillary and surrounding tissue influenced by vascular permeability and structure.In order to solve the instability of numerical calculation caused by convective term,the Characteristic Galerkin(CG)method is employed for the discretization of the advection-diffusion reaction equation through added stabilization term in the equation.The simulated results show that NO concentration in the whole domain decreases when the hydraulic permeability increases remarkably.Moreover,the NO concentration increases in the proximal area after the bifurcation of the capillary and then decreases owing to interplay of the convective effect and WSS variations.Subsequently,the motion of RBCs in a microvessel is investigated by using IB-LBM first and NO distribution inside the microvessel with multiple RBCs is computed by using immersed boundary finite difference method.Using this model,NO concentration distribution can be simulated under different RBC membrane permeability,hematocrit and deformability of RBCs’membrane.The result shows that a decrease of RBC membrane permeability leads to an increase of NO concentration in the vessel and the surrounding endothelium significantly,indicating that RBC membrane acts as a main resistance in NO transport process and helps to maintain NO concentration in microvessel.In addition,with the increasing of Hct value,NO concentration distribution in the whole vessel decreases both in the lumen and vascular wall.Finally,the thickness of CFL gradually decreases with the weakened deformability of RBCs’membrane and the NO concentration in vascular wall is reduced resulting from the thinner CFL.Furthermore,NO concentration distribution is simulated in a microvessel with a microaneurysm based on the same computational framework.The meshes with curved boundaries are generated by a pixel-based mesh generation method,and the entrance and exit of microvessel with variable sections are treated by Zou-He boundary conditions.The results show that the presence of microaneurysm leads to the occurrence of vortex inside the microaneurysm,and then the declining of NO concentration appears due to the lower NO production rate in the microaneurysm.Meanwhile,non-uniformity of NO concentration distribution along the vessel wall becomes distinguished with the vascular curvature increasing.In order to investigate the relationship among microvascular complications,NO concentration and skin blood perfusion,animal models with type 2 diabetes mellitus(T2DM)have been constructed.Parameters of red blood cell,NO concentration level,and blood skin perfusion have been measured.The evaluation of microvascular tone is based on wavelet analysis of the dorsal skin LDF signals of thermal stimulus test in the endothelial,neurogenic,and myogenic frequency ranges.The NO level in plasma is also measured as a marker of endothelial dysfunction.Changes in the microcirculation structure in the diabetic rats were evaluated by measuring the microvascular density of the choke vessels in the dorsal skin of the rats.The experimental results demonstrate that the increasing fluctuation amplitudes diminished in the endothelial frequency range in response to the thermal test,which is accompanied with abnormal NO levels in plasma of the diabetic groups as compared with healthy rats.The experimental results with respect to RBC-related parameters show decreased hematocrit and hemoglobin levels and increased standard deviation of the width of the RBC distribution in all diabetic rats.The microvascular density of the choke vessels in the dorsal skin is found to lessen in the diabetic group at the most advanced stage of diabetes in this experiment.It is thus suggested from the experiment that endothelial dysfunction occurs in almost all stages of diabetic rats and changes of the microvascular structure occurs in the later stage of diabetes mellitus.In summary,the behaviors of NO transport in microvessels are numerically explored using FEM,IB-LBM and IB-FDM and the relationship between diabetic skin blood perfusion and changes of NO concentration is investigated.The developed IBM-based computational method for transmembrane mass transfer of moving deformed particles provides a fresh idea for oxygen transport and drug transport in microcirculation as well.The results in this work not only reveal the changes of NO concentration in various vascular network and tissues,but also provide theoretical help for the development of medical devices for the early diagnosis of diabetic microcirculatory lesions.