Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

PLoS One. 2016 Sep 2;11(9):e0162144. doi: 10.1371/journal.pone.0162144. eCollection 2016.

Abstract

Background: 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 it to human NCIPH.

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

Results: Weekly embolization induced a hyperdynamic circulation, with increased PP. The mesenteric flow and hepatic hydroxyproline content was significantly higher in weekly embolized compared to single embolized rats (mesenteric flow +54.1%, hydroxyproline +41.7%). Mesenteric blood flow and shunt volumes increased, whereas splanchnic vascular resistance was decreased in the weekly embolization group. 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.

MeSH terms

  • Actins / metabolism
  • Animals
  • Disease Models, Animal
  • Endoglin / metabolism
  • Hemodynamics / physiology
  • Humans
  • Hypertension, Portal / etiology*
  • Hypertension, Portal / metabolism
  • Hypertension, Portal / pathology
  • Hypertension, Portal / physiopathology
  • Liver / pathology
  • Liver Circulation / physiology*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / physiopathology
  • Male
  • Mesentery / blood supply
  • Portal Vein / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Resistance / physiology*

Substances

  • Actins
  • Endoglin
  • smooth muscle actin, rat

Grants and funding

The study was supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57 project 18), H. J. & W. Hector Foundation (M60.2), Ernst-Bertha-Grimke (6/15). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.