We undertook a study to evaluate the correlation between morphometric evaluation and cobonimetnic determination of hepatic collagen content, and to analyze the variation among animals as well as among lobes of the same liver in hepatic collagen content after CC14-induced micronodulan cirrho-sis_ The results revealed a significant correlation (r = 0.9458; p < 0.001) between the morphometric and colonimetric methods of collagen evaluation of liver specimens; both methods also significantly distinguished data obtained from controls and from cirrhotic rats (p < 0.0005). After induction of micronodular cirrhosis by chronic CCLi administration, a highly significant variation in hepatic collagen content was observed among animals (p < 00001). By contrast, Materials and Methods i Supported by grants from the Medical Research Council of Canada.

tween individual animals. It has been shown that rabbits This study documents the hepatic morphology and the that are given CHOL simultaneously with diethylstilbestrol ultrastructure of a model of hepatic fibrosis in rabbits.(DES) rapidly develop hepatic fibrosis over a period of several Rabbits were given a cholesterol-supplemented diet weeks, 6-8 but this model has not been studied in detail. The (1%), a stilbestrol diet (10 mg subcutaneously twice a present report describes the hepatic morphology, the ultraweek), or both treatments simultaneously for 7 weeks.structure, and the hepatic collagen content following this Rabbits given the combined treatment developed sinu- The treatments were given for 7 weeks, at which point the animals were killed. One D-C rabbit died before the completion of the study. Hepatic fibrosis develops in a variety of mammals that areThe liver and spleen were exposed under sodium pentobarbital anesfed a cholesterol (CHOL)-supplemented diet.1-5 However, in thesia without prior fasting, and samples were excised, diced, and most species, including the rabbit, the fibrosis is mild, re-fixed by immersion in cold 2.5% glutaraldehyde buffered with 0.1 quires many months to develop, and is highly variable be-mol/L of cacodylate at pH 7.2. This tissue was later postfixed with osmium tetroxide, embedded in Epon 812, and the sections were stained with lead citrate and uranyl acetate. The spleens were cut Abbreviations: CHOL, cholesterol; D-C, diethylstilbestrol-cholesterol; DES, diethylstilinto 5-mm slices and allowed to drain on absorbent paper before bestrol.weighing. The liver slices were fixed in buffered 4% formaldehyde,

It has been suggested that hepatocyte enlargement can lead to compression of the extracellular space (sinusoidal and interstitial) and induce portal hypertension. However, this hypothesis has never been tested by measuring the vascular and extravascular spaces in the intact liver. The aim of the present study was to investigate the effects of chronic alcohol intake on the hepatic microcirculation using Goresky's multiple-indicator dilution technique in the isolated perfused rat liver. Female rat littermates were pair-fed either ethanol (n = 7) or an isocaloric carbohydrate diet (n = 7) for 21 days. As expected, chronic alcohol intake produced a significant increase in liver/body weight ratio (+32%, p less than 0.01) and hepatocyte size (+45%, p less than 0.001), which was accompanied by a marked increase in the cellular water space (control: 3.3 +/- 0.6 ml; ethanol-fed: 4.9 +/- 0.9 ml; p less than 0.001). When expressing data per total liver, the sinusoidal space was similar in the two groups (control: 1.87 +/- 0.2; ethanol-fed: 1.95 +/- 0.2 ml; not significant), whereas the interstitial space was increased in alcohol rats compared to controls (albumin space +58%, p less than 0.01; sucrose space +51%, p less than 0.01). In alcoholic rats, the sinusoidal space was probably stretched, with an overall reduced transversal diameter, as suggested by the reduced values found when data were expressed per gm of liver weight. However, despite this finding and the enlargement of the liver and hepatocytes observed in alcoholic rats, similar values were obtained between the two groups for the portal perfusion pressure and thus the intrahepatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)