A Novel Canine Model of Portal Vein Stenosis Plus Thioacetamide Administration-Induced Cirrhotic Portal Hypertension With Hypersplenism

Abstract

Current large animal models that could closely resemble the typical features of cirrhotic portal hypertension in human have not been well established. Thus, we aimed to develop and describe a reliable and reproducible canine cirrhosis model of portal hypertension. A total of 30 mongrel dogs were randomly divided into four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3 (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months modeling period, liver and spleen CT perfusion, abdominal CT scans, portal hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow, liver, and spleen histology were studied. The animals in group 2 (PVS) developed extrahepatic portosystemic collateral circulation, particularly esophageal varices, without hepatic cirrhosis and portal hypertension. Animals from group 3 (TAA) presented mild cirrhosis and portal hypertension without significant symptoms of esophageal varices and hypersplenism. In contrast, animals from group 4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis, associated with significant portal hypertension and hypersplenism. The combination of PVS and TAA represents a novel, reliable, and reproducible canine cirrhosis model of portal hypertension, which is associated with the typical characteristics of portal hypertension, including hypersplenism.

Experimental model of portal hypertension and esophagogastric varices in minipigs: pressure and endoscopic pilot study

“…After five weeks, this technique replicated the previous results, with the development of portal hypertension and formation of esophageal varices 29 . Similar results were also found in other animal species, ranging in size from small, such as rodents (with esophageal varices identified by portography), to medium, such as dogs [30][31][32][33][34] .…”

Characterization of uncommon portosystemic collateral circulations in patients with hepatic cirrhosis

“…The enrolled patients consisted of 449 cases of liver cirrhosis due to hepatitis B virus (HBV) infection, 63 cases of liver cirrhosis due to hepatitis C virus (HCV) infection, 53 cases of alcoholic cirrhosis, 41 cases of undetermined etiology, 30 cases of primary biliary cirrhosis, 24 cases of autoimmune liver cirrhosis, 13 cases of Budd-Chiari syndrome, nine cases of liver cirrhosis due to HBV/HCV coinfection, five cases of liver degeneration, four cases of drug-induced liver cirrhosis, four cases of overlap syndrome, two cases of hepatic veno-occlusive disease, two cases of portal vein spongiform degeneration and one case of cardiac cirrhosis. The liver function of the patients was classified in accordance with the Child-Pugh classification standard ( 5 ), identifying 227 cases as grade A, 302 cases as grade B and 171 cases as grade C. Written informed consent was obtained from all patients and was approved by the ethics committee of 302 Hospital of the People’s Liberation Army (Beijing, China).…”

“…Once portal hypertension develops, it dramatically alters the extrahepatic vascular beds in the splanchnic and systemic circulation, leading to arterial vasodilation and collateral circulation formation, which diverts a greater proportion of the blood flow into the portal vein. Portal hypertension is exacerbated by the increased portal blood flow, which can also be replicated in canine models ( 5 , 6 ).…”

Thioacetamide promotes osteoclast transformation of bone marrow macrophages by influencing PI3K/AKT pathways

“…TAA-induced cirrhosis has similar pathologic changes to human liver cirrhosis and can be used to reproduce the human disease [2,3] . Additionally, the effects of TAA are not limited to the liver, as profound structural and functional changes have been described in the kidney, spleen, lung, intestine, stomach, brain and bone marrow upon TAA treatment [4][5][6][7][8][9][10][11] . However, less attention has been paid to the association of TAA with bone damage.…”