Evaluation of bile duct ligation-induced portal vein hypertension in telemetered rats

P Guillaume, S Bézivin, S Rompion, M Lemaire, G Froget. Porsolt SAS, 53940, France

Portal vein pressure measurement is an important parameter for the evaluation of liver pathology since the occurrence of portal hypertension is a common consequence of human chronic liver diseases. A classic animal model for studying the effects of chronic liver disease is the rat Bile Duct Ligation (BDL) model. Usually, only terminal measures are performed. The aim of this work was to evaluate the use of telemetry for continuous measurement of portal vein pressure after BDL in the conscious freely-moving rat.

Male Wistar (Han) rats (277-305g) were implanted with telemetric devices for portal vein pressure recording and were submitted to BDL (Day 1). Telemetry recordings were then taken up to 3 weeks after BDL to compare portal vein pressure values of BDL rats (n=6) to those obtained in sham-operated rats (n=7). Daily body weights were recorded. At necropsy, organs weights (heart, liver, spleen and kidneys) were also reported. Data were analysed by comparing treated groups with control groups using unpaired Student\'s t tests.

Body weight decreased the first week following BDL (299 ± 8 g in BDL rats versus 317 ± 4 g in sham-operated rats on Day 7, i.e. -6%). Then, the body weight gain was similar between sham and BDL rats,

Weights of the liver, spleen and kidneys were significantly increased in BDL rats (liver: 5416.7 ± 518.5 versus 4072.1 ± 100.2 mg/100g body weight, i.e. +33%, p < 0.05; spleen: 689.8 ± 84.1 versus 314.1 ± 18.0 mg/100g body weight, i.e. +120%, p < 0.001; left kidney: 412.6 ± 29.9 versus 344.1 ± 9.5 mg/100g body weight, i.e. +20%, p < 0.05; right kidney: 409.8 ± 28.0 versus 352.2 ± 9.8 mg/100g body weight, i.e. +16%, NS) while the weight of the heart was significantly reduced (290.9 ± 7.7 versus 355.0 ± 13.2 mg/100g body weight, i.e. -18%, p < 0.01).

BDL induced an increase in mean portal vein pressure over the whole period of evaluation, (significantly from Day 8). The mean increase in mean portal pressure reached 7.2 ± 0.4 mmHg compared to sham rats (ranging from +5.1 mmHg to +10.4 mmHg).

These results suggest that telemetry is a valuable technique for studying the longitudinal effects of drug candidates in the rat Bile Duct Ligation-induced portal vein hypertension model.