Vascular corrosion casting: analyzing wall shear stress in the portal vein and vascular abnormalities in portal hypertensive and cirrhotic rodents

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.

Increased intrahepatic resistance in severe steatosis: endothelial dysfunction, vasoconstrictor overproduction and altered microvascular architecture

“…Filling of the blood vessels with a casting polymer and subsequent removal of all the surrounding tissue allows for an accurate and three-dimensional study of the vascular structures by scanning electron microscopy at high levels of magnification that cannot be achieved by angiography-based imaging techniques, which do not attain the same resolution at the microvascular level. 26,39 The casts of the animals with steatosis showed a marked alteration of liver microvascular architecture. The classical ordering of sinusoids in parallel lines and separated by regular trabeculae of hepatocytes was replaced by a completely disorganized pattern of irregular and flattened blood vessels with numerous interconnections and the presence of multiple 'blebs', that is, blind-ending rounded extensions of the sinusoids, which might represent obstructed sinusoids or leakage by disruption of the normal sinusoidal wall.…”

“…15 Vascular Corrosion Casts Vascular corrosion casting was performed as previously described. 26 After overnight fasting animals fed the MCD diet (n ¼ 5) or the control diet (n ¼ 5) were killed by means of an intraperitoneal injection of an overdose of a solution containing 0.8 ml ketamin (Anesketin, Eurovet, Heusden-Zolder, Belgium) and 0. Methoxamine and ACh were purchased from Sigma-Aldrich Chemie Gmbh, Steinheim, Germany.…”

Intussusceptive Angiogenesis: A Biologically Relevant Form of Angiogenesis

“…IA has been observed in different murine disease models, including models of liver cirrhosis, models of inflammation, and the hypoxic mouse retina [56,57,58]. In addition, IA was observed to start glomerular repair after induced Thy-1.1 nephritis in rats [59,60].…”

Closed-Loop Lumped Parameter Modeling of Hemodynamics During Cirrhogenesis in Rats

“…Geometries were Closed-loop lumped parameter modelling of hemodynamics during cirrhogenesis in rats based on CT-scans and results indicated that -in the case of cirrhosis -right-lobe atrophy was significantly influenced by the distribution of splenic venous blood. Van Steenkiste et al [11] used vascular corrosion casting (VCC) to study vascular morphological changes and CFD simulations to compute PV wall shear stresses in portal hypertensive and cirrhotic rodents. Additional to the macrocirculatory research, only few studies have focused on modelling the hepatic microcirculation of healthy and cirrhotic livers.…”