A stable model of cirrhotic portal hypertension in the rat: thioacetamide revisited

European Journal of Clinical Investigation
W LalemanF Nevens

Abstract

Cirrhotic animal models are vital to investigate complications of chronic liver disease. We chronologically characterized the effect of thioacetamide, administrated orally and adapted weekly to weight changes, focusing on the optimal moment to obtain all typical features of portal hypertension and cirrhosis. Male Wistar rats, 200-250 g, were intoxicated for 6, 12 or 18 weeks (n = 8 per group), respectively, and compared with age-matched controls (n = 4 per group). An in-situ perfusion model was used to evaluate intrahepatic resistance and endothelial function. Splanchnic blood flow and portosystemic shunting were assessed by a perivascular flow probe. Rats intoxicated for 6 or 12 weeks had no mortality and histologically showed hepatitis and advanced fibrosis, respectively. At 18 weeks, mortality was 16% (on a total of 56 animals) and only at that moment all animals showed homogenous macronodular cirrhosis with signs of high-grade hepatocellular dysplasia. Portal hypertension was present at 12 weeks (11 +/- 0.4 vs. 5.9 +/- 0.4 mmHg, P < 0.001), but was not associated with the hyperdynamic state until 18 weeks (12.1 +/- 0.8 vs. 5.6 +/- 0.5 mmHg, P < 0.001). At this latter time-point, we also observed increased intrahepatic resis...Continue Reading

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