Restrictive Model of Compensated Carbon Tetrachloride-induced Cirrhosis in Rats

Aim: To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats.

Methods: In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachloride (CCl4) (dilution 50%) gavage to induce cirrhosis (frequency adjusted according to weight, but each subsequent dose was systematically administered) were tested, i.e. the rapid and slow protocols. Prothrombin time (PT) and total bilirubin (TB) were also evaluated. Animals from the rapid group underwent 15% hepatectomy and animals from the slow group underwent 70% hepatectomy.

Results: Rapid protocol: This corresponded to 1 gavage/4 d over 6 wk (mortality 30%). Mean PT was 35.2+/-2.8 s (normal: 14.5 s), and mean TB was 1.8+/-0.2 mg/dL (normal: 0.1 mg/dL). Slow protocol: This corresponded to 1 gavage/6 d over 9 wk (mortality 10%). Mean PT was 11.8+/-0.2 s (normal: 14.5 s), and mean TB was 0.4+/-0.04 mg/dL (normal: 0.1 mg/dL). Pathological analyses were performed in both protocols which showed persistent cirrhosis at 3 mo. Rat mortality in the rapid gavage group who underwent 15% hepatectomy and in the slow gavage group who underwent 70% hepatectomy was 50% and 70%, respectively.

Conclusion: Our modified model is a simplified method to induce cirrhosis which is rapid (6 to 9 wk), efficient and stable up to 3 mo. Using this method, "Child Pugh A" or "Child Pugh BC" cirrhotic rats were obtained. Our models of cirrhosis and hepatectomy can be used in various situations focusing on postoperative survival.