Controlled induction of cirrhosis in the rat

The production of experimental cirrhosis in the rat, most commonly by multiple doses of carbon tetrachloride (CCl4), is a difficult process with a low yield of "cirrhosis" of widely varied histology. This is due to an unpredictable variation in the response of the rat liver to CCl4, and the lack of a reliable method of monitoring the rapidly changing liver damage with each dose. A simple non-invasive method is described in which the daily body weight change of the rat in response to weekly intragastric doses of CCl4 has been shown empirically to sufficiently reflect the state of the liver as to enable each dose of CCl4 to be calibrated by the weight change of the previous dose. The death rate is markedly reduced and a critical level of liver damage can be maintained. This improved control over liver damage has made it possible to produce a high yield (72%) of a standardized decompensated micronodular cirrhosis with 8-10 doses of CCl4. Under these weight-calibrated conditions this point is determined non-invasively by using a visual grading of a critical level of ascites estimated during light halothane/oxygen anaesthesia to relax the abdominal musculature.