The Rat Liver Microcirculation in Alcohol–Induced Hepatomegaly

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Abstract
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 < 0.01) and hepatocyte size (+45%, p < 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 < 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 < 0.01; sucrose space +51%, p < 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. The present data show that the enlargement of the liver and hepatocytes due to chronic alcoholic intake: (i) does not develop at the expense of the total vascular space and unexpectedly increases the interstitial space, and (ii) under our experimental conditions, does not modify the overall resistance of the liver.