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Modeling the effect of blood vessel bifurcation ratio on occlusive thrombus formation.

ABSTRACT: Vascular geometry is a major determinant of the hemodynamics that promote or prevent unnecessary vessel occlusion from thrombus formation. Bifurcations in the vascular geometry are repeating structures that introduce flow separation between parent and daughter vessels. We modelled the blood flow and shear rate in a bifurcation during thrombus formation and show that blood vessel bifurcation ratios determine the maximum shear rate on the surface of a growing thrombus. We built an analytical model that may aid in predicting microvascular bifurcation ratios that are prone to occlusive thrombus formation. We also observed that bifurcation ratios that adhere to Murray's law of bifurcations may be protected from occlusive thrombus formation. These results may be useful in the rational design of diagnostic microfluidic devices and microfluidic blood oxygenators.

SUBMITTER: Lakshmanan HHS

PROVIDER: S-EPMC6736679 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Modeling the effect of blood vessel bifurcation ratio on occlusive thrombus formation.

Lakshmanan Hari Hara Sudhan HHS Shatzel Joseph J JJ Olson Sven R SR McCarty Owen J T OJT Maddala Jeevan J

Computer methods in biomechanics and biomedical engineering 20190508 11

Vascular geometry is a major determinant of the hemodynamics that promote or prevent unnecessary vessel occlusion from thrombus formation. Bifurcations in the vascular geometry are repeating structures that introduce flow separation between parent and daughter vessels. We modelled the blood flow and shear rate in a bifurcation during thrombus formation and show that blood vessel bifurcation ratios determine the maximum shear rate on the surface of a growing thrombus. We built an analytical model ...[more]

PMID: 31066295

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Project description:Endothelial barrier function is known to be regulated by a number of molecular mechanisms; however, the role of biomechanical signals associated with blood flow is comparatively less explored. Biomimetic microfluidic models comprised of vessel analogues that are lined with endothelial cells (ECs) have been developed to help answer several fundamental questions in endothelial mechanobiology. However, previously described microfluidic models have been primarily restricted to single straight or two parallel vessel analogues, which do not model the bifurcating vessel networks typically present in physiology. Therefore, the effects of hemodynamic stresses that arise due to bifurcating vessel geometries on ECs are not well understood. Here, we introduce and characterize a microfluidic model that mimics both the flow conditions and the endothelial/extracellular matrix (ECM) architecture of bifurcating blood vessels to systematically monitor changes in endothelial permeability mediated by the local flow dynamics at specific locations along the bifurcating vessel structure. We show that bifurcated fluid flow (BFF) that arises only at the base of a vessel bifurcation and is characterized by stagnation pressure of ?38 dyn cm-2 and approximately zero shear stress induces significant decrease in EC permeability compared to the static control condition in a nitric oxide (NO)-dependent manner. Similarly, intravascular laminar shear stress (LSS) (3 dyn cm-2) oriented tangential to ECs located downstream of the vessel bifurcation also causes a significant decrease in permeability compared to the static control condition via the NO pathway. In contrast, co-application of transvascular flow (TVF) (?1 ?m s-1) with BFF and LSS rescues vessel permeability to the level of the static control condition, which suggests that TVF has a competing role against the stabilization effects of BFF and LSS. These findings introduce BFF at the base of vessel bifurcations as an important regulator of vessel permeability and suggest a mechanism by which local flow dynamics control vascular function in vivo.

Dataset Information

Modeling the effect of blood vessel bifurcation ratio on occlusive thrombus formation.

Publications

Modeling the effect of blood vessel bifurcation ratio on occlusive thrombus formation.

Similar Datasets

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