Novel rat model of repetitive portal venous embolization mimicing human non-cirrhotic idiopathic portal hypertension

Background: The non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics, and compared to human NCIPH.

Methods: Portal pressure was measured invasively and coloured microspheres were injected in the portal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization (single embolization) served as controls. After three weeks hemodynamics were investigated, hepatic fibrosis and accumulation of myofibroblasts were analysed. General characteristics, laboratory analyses and liver histology were collected in five patients with NCIPH.

Results: Weekly embolization induced hyperdynamic circulation, with increased portal pressure. The mesenteric flow and hepatic hydroxyproline was significantly higher in weekly embolized compared to single embolized rats (mesenteric flow +54.1%, hydroxyproline +41.7%). Mesenteric blood flow and shunt volume were increased, whereas splanchnic vascular resistance was decreased in the weekly embolization group. The fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats.

Discussion: This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies.