BACKGROUND:  Non-cirrhotic portal hypertension is a common cause of portal hypertension in developing countries. To understand its etiopathogenesis we developed an animal model by repeated portal endotoxemia induced through the gastrosplenic vein.
METHODS: Twenty-nine rabbits (1.5-2.0 kg) were divided into control (group I, n=13) and experimental (group II, n=16) groups. Heat killed E.coli were injected through an indwelling cannula into the gastrosplenic vein in pre-sensitized animals. The animals were sacrificed at 1, 3 and 6 months.
RESULTS: The mean portal pressure in group II animals was significantly (P<0.05) higher than in  group I at 1 (17.5±3.4 vs 10.4±2.2 mmHg), 3 (17.8±1.3 vs 7.2+3.6 mm Hg), and 6 (19.8±3.1 vs 10.3±4.8 mmHg) months. Similarly, the mean splenic weight in group II was significantly greater than in group I (P<0.05). Histopathologically, the  spleen showed medullary congestion, hemosidrin-laden macrophages and mild fibrosis. Histologically, the liver had normal parenchyma with mild portal lymphocytic infiltrates and kupffer cell hyperplasia. No significant anomalies were detected by liver function tests.
CONCLUSIONS: The rabbit model showed significant splenomegaly with a persistent  increase in portal pressure and mild fibrosis without hepatic parenchymal injury, quite akin to non-cirrhotic portal fibrosis as seen in humans. Recurrent intra-abdominal infection may play an important role in the pathogenesis of non-cirrhotic portal fibrosis.