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Systemic and splanchnic hemodynamics of the chronic bile duct-ligated rat were characterized by radioactive microspheres. Conscious and pentobarbital sodium-anesthetized, bile duct-ligated and sham-operated rats had cardiac output and regional organ blood flows determined. The conscious bile duct-ligated rat compared with the sham-operated showed a hyperdynamic circulation with an increased cardiac output (153.3 +/- 9.8 vs. 112.6 +/- 6.0 ml/min, P less than 0.005) and portal tributary blood flow (21.32 +/- 1.43 vs. 12.79 +/- 1.47 ml/min, P less than 0.005). Pentobarbital sodium anesthesia induced marked hemodynamic changes in both sham-operated and bile duct-ligated rats. The latter group was especially sensitive to its effects; thus, comparison of cardiac output and portal tributary blood flow between anesthetized bile duct-ligated and sham-operated rats showed no significant differences. We conclude that the rat with cirrhosis due to chronic bile duct ligation is an excellent model for hemodynamic investigations but should be studied in the conscious state, since pentobarbital sodium anesthesia eliminates the hyperdynamic circulation.

Cardiac responses to catecholamines are known to be attenuated in chronic liver disease. To elucidate the role of beta-adrenergic receptor alteration in this phenomenon, we measured heart rate responsiveness to isoprenaline and myocardial beta-adrenergic receptor-binding characteristics in three groups of rats: those that were sham operated, those that had portal vein stenosis and those that were cirrhotic because of bile duct ligation. Responsiveness to isoprenaline was evaluated in conscious rats by the dose of isoprenaline needed to increase basal heart rate by 50 beats/min and by the maximal heart rate response. beta-Receptor characteristics in heart membranes were derived from 125I-iodocyanopindolol binding data. Compared with sham-operated controls, cirrhotic rats needed a significantly higher dose of isoprenaline to raise basal heart rate by 50 beats/min (102.3 +/- 19.1 vs. 28.3 +/- 11.3 ng/kg) and lower maximal heart rate response (104 +/- 29 vs. 158 +/- 61 beats/min). In addition, myocardial beta-receptor density was significantly lower in cirrhotic rats (26.5 +/- 4.6 vs. 37.5 +/- 10.3 fmol/mg protein) and the dissociation constant was higher (31.6 +/- 17.0 vs. 14.0 +/- 2.5 pmol/L). Analysis of beta 1/beta 2 subpopulations revealed that the decreased total beta-receptor density was entirely due to selective beta 1-receptor down-regulation. beta-Receptor affinity for agonist was not altered in cirrhotic rats. Rats with portal vein stenosis showed no significant differences in either isoprenaline responsiveness or beta-receptor characteristics when compared with controls. These results indicate that beta-adrenergic receptor down-regulation may be responsible for the myocardial hyporesponsiveness to catecholamines observed in cirrhosis.

SUMMARY Systemic and splanchnic haemodynamics were studied in patients with cirrhosis who had been classified in three groups (A, B, and C) according to the degree of liver failure (modified Pugh's classification). In patients of group A, cardiac index was significantly lower than that of group C and systemic vascular resistance was higher, but not significantly so, than that of patients with liver failure. Wedged hepatic venous pressure was significantly lower in the former group than in the latter. In patients in group B, corresponding values fell between those of groups A and C. Azygos blood flow averaged 0-477±0+242 1/min (mean±SD) in group A and it was significantly lower than in groups B and C (0(642±0+224 and 1[061±0*476 1/min, respectively). In the three groups, acute administration of propranolol induced statistically significant changes in systemic and splanchnic haemodynamics. In patients of group C but not of group B, the mean value of azygos blood flow after propranolol remained significantly higher than in group A. Moreover, the fraction of azygos blood flow to cardiac output decreased in groups A and B while slightly increased in group C. This study shows that in patients with cirrhosis, the degree of liver failure may be a determinant for the haemodynamic responses to drugs acting on portal hypertension. second, to evaluate the haemodynamic effects of propranolol according to the degree of liver failure in patients with cirrhosis.

SUMMARY The endoscopic features of the gastric mucosa in patients with cirrhosis have not been systematically investigated. In these patients, we observed an endoscopic aspect, consisting of multiple small erythematous areas, outlined by a subtle yellowish network (resembling a mosaic), mainly located in the proximal part of the stomach. We tested the value of this sign by comparing two groups: 100 patients with portal hypertension due to cirrhosis, and 300 control patients without signs of liver disease or portal hypertension. This endoscopic pattern was observed in 94 of the patients with cirrhosis, whereas oesophageal varices were seen in 78 only. In contrast, only one patient of the control group had this aspect. Moreover, this sign was also found in seven of eight patients with non cirrhotic portal hypertension, but was seen neither in 100 patients with chronic alcoholism but without liver disease, nor in 10 cirrhotic patients with end-to-side portacaval shunts. These endoscopic changes might be because of mucosal and/or submucosal oedema and congestion highlighting the normal areae gastricae pattern and related to raised portal pressure. We conclude that the mosaic pattern of the gastric mucosa is a sensible and specific sign for diagnosis of portal hypertension, whatever the cause.In patients with cirrhosis, gastrointestinal bleeding related to portal hypertension may be caused by either ruptured oesophageal varices or acute gastric lesions.2 4 Oesophageal varices mucosal changes in these patients are well documented and might have pronostic value.5 In contrast, very little information is available on the gastric mucosa. We observed during upper endoscopic examination, of patients with cirrhosis, multiple erythematous areas, mainly in the fundus, rectangular or diamond-shaped (2-6 mm in diameter), outlined by a delicate white or yellowish network, resembling a mosaic (Figure). Moreover, during emergency endoscopy for upper gastrointestinal bleeding in patients with cirrhosis, we noticed multiple red spots located in the centre of these areas (Figure). The aim of the prospective study described is to determine if this sign has a true significance for the diagnosis of cirrhosis and/or portal hypertension and to test its sensitivity and specificity.

SUMMARY We report on clinical, nutritional, and hepatic histological findings in 50 non-selected obese subjects (mean overweight +74%; range +21-138%). The pathogenesis of the liver damage was assessed with the help of multidimensional analysis of a number of clinical variables. According to the severity of the hepatic lesions, the patients have been ranged in five groups: 0 (normal liver) 10%; I (fatty liver) 48%; II (fatty hepatitis) 26%; III (fatty fibrosis) 8%; IV (fatty cirrhosis) 8%. The more severe changes (groups III and IV) were constantly associated with excessive alcohol intake. The multidimensional analysis was unable to find a relationship between obesity and the development of fibrosis and cirrhosis whereas it showed that: (a) there was a highly significant correlation between the daily ethanol intake and the degree of overweight, (b) severe fatty metamorphosis was significantly associated with the degree of overweight, the existence of diabetes mellitus, and the amount of alcohol and fat intake, (c) nutritional factors, in particular deficient protein intake, have only an accessory effect in the development of mild inflammation and fibrosis, (d) the consumption of potentially hepatotoxic drugs, very high in the obese (about five drugs per day) could have a role in the development of cirrhosis. In conclusion in our study, there was no evidence that obesity per se could result in severe liver damage.Controversy exists in the literature about the incidence and nature of liver lesions in obese patients. In most studies fatty liver was the only significant abnormality,1-4 but recent reports have suggested that severe liver damage, sometimes mimicking the entire histological spectrum of alcoholic liver disease, could be found in obesity.512In most of these studies, however, information on the potential hepatotoxic factors occuring in obesity was usually lacking. Thus, we undertook a crosssectional study of the liver histology in 50 nonselected obese patients with the aims: (a) to define precisely the prevalence, the nature, and the severity of the liver lesions in obesity; (b) to determine, by the multidimensional analysis, the quantitative and/or qualitative clinical variables which were related to the observed histological abnormalities. Methods PATIENTSFifty obese patients, consecutively hospitalised in a

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