Animal models of portal hypertension

Abstract

Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model, depending on the specific objectives of the study, are also discussed.

Figure 1

Summary of the pathophysiology of portal hypertension. The increase in hepatic resistance leads to an increase in portal pressure. This leads to a cascade of disturbances in the splanchnic and systemic circulation characterized by vasodilation, sodium and water retention and plasma volume expansion, that are major players in the pathogenesis of ascites and hepato-renal syndrome. Additionally, these alterations lead to an increase in portal blood inflow that contributes to maintain and aggravates portal hypertension. Another characteristic feature is the development of porto-systemic collaterals that are resposible for complications such as variceal bleeding and hepatic encephalopathy.

Figure 2

A comparison of microscopic aspect of a liver 6 wk after CBDL (A) and 12 wk after TAA (B) administration.

Figure 3

Macroscopical images of livers from CCl₄ (A) and TAA (B) models.

Figure 4

Model of portal hypertension-related bleeding. In these model a section of a first (1), second (2), third (3) or fourth order branch of the ileocolic vein is isolated and sectioned[14,25,82].