Quantitative analysis of hepatic macro‐ and microvascular alterations during cirrhogenesis in the rat

Abstract

Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions.

Combined Ultrasound and Nerve Stimulator-Guided Deep Nerve Block May Decrease the Rate of Local Anesthetics Systemic Toxicity: A Randomized Clinical Trial

“…Patients with chronic liver disease usually have vascular dysfunction, especially angiogenesis, microvascular derangements and microcirculatory dysfunction [26,27]. Cirrhosis causes numerous microscopic vessel aberrations, and these vessels may become entangled with each other, resulting in sharp bends, anomalous branching patterns, abnormal branching angles and tortuosity [28]. McAvoy et al [29] demonstrated that patients with cirrhosis had selective regional increases in blood flow in the splanchnic and hepatic circulations but diminished flow in the peripheral limbs.…”

Corrosion casting in anatomy: Visualizing the architecture of hollow structures and surface details

“…different in contrast or colour), it is highly recommended to perform the casting simultaneously. When this cannot be achieved for logistic reasons, sequential casting can also be considered, but it is then imperative that the hepatic arterial system is filled first (Peeters et al, ). Not only can the engorgement of the portal vein with casting medium hamper the swift filling of the much smaller hepatic arterial system, in some animals such as rodents, pre‐sinusoidal one‐directional shunting vessels that are able to shift content from the arterial system to the venous system are present in the liver (Kline et al, ).…”

“…Only when the portal vein is subsequently injected with uncontrasted resin, the shunted, contrasted resin is pushed further towards the liver sinusoids and hepatic veins, where a mixed (attenuated) contrast is normally expected. As the shunts work unidirectionally, uncontrasted resin cannot enter the hepatic arterial system prematurely (Kline et al, ; Peeters et al, ).…”

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

“…During the morphological analysis, two portosystemic shunts were detected in one of the cirrhotic rats (cirrhosis 2) (illustrated in [22]), shunting blood directly from the portal trunk into the caudal vena cava. In addition, previous research documented that blood flow through the splenorenal shunt was multiplied by 3.5 in the case of TAA cirrhotic rats [15].…”

“…To gather data across the entire length scale, ranging from the major blood vessels down to the smallest liverspecific capillaries (sinusoids), exponential trend lines were fitted to the geometrical attributes as a function of the generation number using a lobe-specific fitting algorithm (previously described in [16]). The total number of generations for each PV and HV lobar vascular tree was estimated by extrapolating the radius until reaching mean values representing sinusoids (reported in [22]). For 0, 6, 12, and 18-weeks intoxications, mean sinusoidal radii were measured to be 4.35 ± 0.22 µm, 4.29 ± 0.33 µm, 3.87 ± 0.38 µm, and 3.90 ± 0.45 µm, respectively.…”