Abstract

Vascular corrosion casting is an established method of anatomical preparation that has recently been revived and has proven to be an excellent tool for detailed three-dimensional (3D) morphological examination of normal and pathological microcirculation. In addition, the geometry provided by vascular casts can be further used to calculate wall shear stress (WSS) in a vascular bed using computational techniques. In the first part of this study, the microvascular morphological changes associated with portal hypertension (PHT) and cirrhosis in vascular casts are described. The second part of this study consists of a quantitative analysis of the WSS in the portal vein in casts of different animal models of PHT and cirrhosis using computational fluid dynamics (CFD). Microvascular changes in the splanchnic, hepatic and pulmonary territory of portal hypertensive and cirrhotic mice are described in detail with stereomicroscopic examination and scanning electron microscopy. To our knowledge, our results are the first to report the vascular changes in the common bile duct ligation cirrhotic model. Calculating WSS using CFD methods is a feasible technique in PHT and cirrhosis, enabling the differentiation between different animal models. First, a dimensional analysis was performed, followed by a CFD calculation describing the spatial and temporal WSS distributions in the portal vein. WSS was significantly different between sham/cirrhotic/pure PHT animals with the highest values in the latter. Up till now, no techniques have been developed to quantify WSS in the portal vein in laboratory animals. This study showed for the first time that vascular casting has an important role not only in the morphological evaluation of animal models of PHT and cirrhosis, but also in defining the biological response of the portal vein wall to hemodynamic changes. CFD in 3D geometries can be used to describe the spatial and temporal variations in WSS in the portal vein and to better understand the forces affecting mechanotransduction in the endothelium.

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