The Rat Liver Microcirculation in Alcohol–Induced Hepatomegaly

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 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)

HIF-1α induction suppresses excessive lipid accumulation in alcoholic fatty liver in mice

“…Prolonged hypoxia has been reported to cause mitochondrial dysfunctions through producing reactive oxygen species, impairing mitochondrial fatty acid oxidation and in turn stimulating lipid synthesis in the ethanol-treated liver [1]. These hypoxic alterations with continuous ethanol consumption accelerate fat infiltration into hepatocytes and lead to a dramatic increase in the size of hepatocytes [4]. As a consequence of impairment of hepatic microcirculation, presumably due to mechanical oppression by swollen hepatocytes and increased sinusoidal contractility of non-parenchymal cells in response to constrictors such as endothelin-1 [5], hypoxic damage processes and fat accumulation might further be exacerbated concomitantly.…”

Hepatic circulation: Potential for therapeutic intervention

“…They found an increase in total liver volume, with an increase in cellular and interstitial volumes but no significant change in sinusoidal volume. Furthermore, intrahepatic portal resistance of the perfused liver and portal pressure in vivo (Mastai et al, 1989) were not significantly modified. Finally, administration of alcohol, in CCl4-induced cirrhotic rats, did not further increase portal pressure measured in vivo in conscious animals, in spite of a significant increase in liver cell volume assessed by morphometry (Huet et al, unpublished data).…”

Even the french foie gras de canard does not induce portal hypertension

“…The main point of contention appears to center on the validity of the measurement of portal pressure using the intrahepatic pressure method that we used in our studies. This doubt is based on the study by the Montreal group previously published in Hw.4v)i.om ( 1 ). We wish to note that the findings in such a study are at variance with those reported in the literature by seven other groups (2-7, Gibson PR, HEPAWIAX;Y 1988;8: 1723, Correspondence) that, when combined, yield a mean correlation between intrahepatic and portal pressures of r = 0.91 2 0.05 (S.D.)…”

“…Blendis and Israel regarding our paper on "the rat liver microcirculation in alcohol-induced hepatomegaly" ( 1 ) .…”