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At least 19 recordsLinked to original sources
PubMed1993

Region-selective reductions in activities of glutamine synthetase in rat brain following portacaval anastomosis.

Portacaval anastomosis in the rat results in liver atrophy, sustained hyperammonemia and mild encephalopathy. Previous studies have demonstrated region-selective alterations of glutamine and other ammonia-related amino acids in brain following portacaval anastomosis. Ammonia removal by brain relies on glutamine synthesis and the enzyme responsible, glutamine synthetase, has an almost exclusively astrocytic localization. Glutamine synthetase activities were measured using a radioenzymatic assay in homogenates of seven brain regions of rats four weeks after end-to-side portacaval anastomosis. Enzyme activities were significantly reduced in hippocampus (by 25%, p < 0.01), in cerebellum (by 29%, p < 0.01) and in cerebral cortex (by 14%, p < 0.05). Enzyme activities in other brain regions were within normal limits. Region-selective reductions of glutamine synthetase following portacaval anastomosis could result in disruption of neuron-glial metabolic interactions and in a deficit of glutamatergic synaptic regulation. Similar mechanisms could be implicated in the pathogenesis of hepatic encephalopathy accompanying chronic liver disease in humans.

Ammonia↗
PubMed1978

Neurotransmittor changes in the rat brain after portacaval anastomosis.

Portacaval anastomosis in rats elevated the brain serotonin content by about 30%, the greatest increase being noted in the brain stem. A minor increase in norepinephrine content but no change in dopamine concentration was also noted. Low dose L-dopa treatment reversed the serotonin changes but did not affect catecholamine concentrations. Protein load tended to lower most transmittor concentrations without clinically affecting the animals. The formation of 5-HT from tryptophane in vitro in rat cortical slices was reduced by about 35% whereas the formation of 5-HIAA in the same slices was increased with about 60%. This in vitro study indicates a change in the activity of serotonin neurons caused by the protacaval shunt. The findings suggest that changes in brain serotonin metabolism and brain serotonin neurons may be an explanation of hepatic encephalopathy.

Animals↗
PubMed1993

[Effect of MHS-G, an amino acids granule, on hepatic encephalopathy in portacaval anastomosis rats].

Using portacaval anastomosis (PCA) rats as a model with or without injection of ammonium acetate, we investigated the effects of MHS-G on the abnormalities of electroencephalogram (EEG) and brain amines metabolism in comparison with those of SF-1008C, a commercial nutritional preparation for hepatic failure. MHS-G (0.68 g/kg, p.o.) clearly improved both the abnormalities of EEG (such as reduction of amplitude, increasing delta wave distribution and decreasing beta wave distribution) and brain amines metabolism (such as increasing of Trp and DOPAC content) after injection of ammonium acetate. Moreover, MHS-G significantly increased branched chain amino acid concentrations and decreased aromatic amino acid concentrations in plasma and brain in comparison with water, and it significantly decreased the ammonia level in plasma in comparison with water and SF-1008C. These results suggest that MHS-G has a positive effect on abnormalities of EEG and amino acids metabolism in the plasma and brain of PCA rats.

Acetates↗
PubMed1977

Modifications of 3'-methyl-4-dimethylaminoazobenzene carcinogenesis of rat liver and carcinogen metabolism by portacaval anastomosis.

The effect of portacaval shunt on hepatocarcinogenesis was studied in rats fed 3'-methyl-4-dimethylaminoazobenzene. Portacaval anastomosis resulted in a decrease of hepatocarcinogenesis as reflected by a delay in the early peak of alpha-fetoproteins, an absence of late appearance of alpha-fetoproteins, and a significantly lower incidence of tumors than in nonshunted rats. Reduction of hepatocarcinogenesis in shunted rats was associated with a decrease of the binding of 3'-methy-4-dimethylamioazobenzene metabolites to liver proteins. This effect seemed to be related to modifications of carcinogen-metabolic pathways. While the detoxifying azoreductase activity was not affected by portal diversion, the activating pathway leading to the binding of 4-dimethylaminoazobenzene metabolites to DNA, a major step for cell carcinogenesis that is mediated by microsomal enzymes, was decreased in shunted rats to about 50 percent of control values. The decrease of liver weight that occurred in shunted rats without loss of body weight produced a very significant reduction of the total capacity of liver to activate 4-dimethylaminoazobenzene while the total capacity of detoxification remained unchanged. This could be a direct consequence of portacaval anastomosis, as has been shown for other microsomal enzymes.

Animals↗
PubMed1985

Efficient hepatic uptake of chylomicron remnant cholesterol in rats with a portacaval anastomosis.

Portacaval-shunted and sham-operated male rats, fed ad libitum and of similar weight, were studied 2-3 weeks after surgery. At this time serum cholesterol levels did not differ significantly between the two groups, whereas serum triacylglycerols and phospholipids were lower in the shunted group. These animals also showed an increased serum bile acid level and an increased serum estradiol to testosterone ratio. The metabolism of native chyle labeled with [3H]cholesterol and [14C]linoleic acid or of preformed chylomicron remnants with the same labeling was studied in the groups of rats. Ten minutes after intravenous injection of chylomicron remnants 10.6 +/- 0.5% (means +/- SEM, n = 8) of the injected [3H]cholesterol and 7.6 +/- 0.4% of the [14C]linoleic acid were found per 1 g liver in the portacaval-shunted rats; the corresponding figures in the sham-operated group (n = 8) were 6.4 +/- 0.4 and 4.9 +/- 0.3, respectively (p less than 0.001 for both 3H and 14C). Thus, despite a greater than 40% reduction of liver weight induced by the shunting procedure, the total liver uptake of chylomicron remnants was not significantly decreased. The uptake of chylomicron lipids per unit liver weight was normal in the atrophic livers of portacaval-shunted rats also when very large loads of chyle were administered.

Animals↗
PubMed1992

Prognostic factors of hepatic encephalopathy after portacaval anastomosis: a multivariate analysis in 50 patients.

Portacaval anastomosis has proved to be effective in avoiding active and recurrent hemorrhage from gastroesophageal varices in liver cirrhosis. However, hepatic encephalopathy is the most common and serious complication of this procedure. The aim of this study was to investigate by multivariate analysis the predictive factors of development of hepatic encephalopathy in 50 Child's A and B cirrhotic patients whose variceal bleeding was treated with emergency (n = 17) or elective (n = 33) portacaval anastomosis. The etiology of the cirrhosis was alcoholic in 74% of cases. The mean follow-up was 22.7 +/- 16.6 months (range 1-60 months). The 2-yr probability of suffering from at least one episode of hepatic encephalopathy in the overall group was 43%. The multivariate analyses (Cox's regression method) of 37 variables based upon clinical history, physical examination, and laboratory data disclosed that only five of these variables had independent predictive value: need for diuretic treatment in the days prior to surgery, absence of hepatomegaly, and serum levels of total bilirubin, gamma-globulin, and hemoglobin. According to the contribution of each one of these factors to the final model, a prognostic index was obtained which allowed the division of patients in two different groups of risk for developing hepatic encephalopathy (20% and 74%, respectively, after 2 yr of surgery; p = 0.0002). This index may help to better choose those candidates for portacaval anastomosis.

Adult↗
PubMed1987

Lipoprotein catabolism in rats with portacaval anastomosis on various diets.

The catabolism of lipoproteins was measured in rats with a portacaval anastomosis and in intact control rats. Radioiodinated rat high density lipoproteins or human low density lipoproteins, the major cholesterol-bearing lipoproteins in rat or man respectively, were injected intravenously into rats. More than 90% of trace amounts of these lipoproteins were removed from plasma of rats with portacaval anastomosis and controls on standard chow at closely similar rates within 24 h. Also, [125I]high density lipoproteins left the plasma at comparable rates in controls and rats with portacaval anastomosis, whether fed with a cholesterol-free chow or a carbohydrate-rich lard chow. These dietary regimens were employed to avoid artifacts through a different development of the body weight in operated and control rats. A standard laboratory chow ad libitum led to weight loss in rats with portacaval anastomosis. Pair-fed with a cholesterol-free chow both groups of rats kept the same weight, but only with a carbohydrate-rich lard chow could the natural weight gain be achieved. In all rats with portacaval anastomosis liver weights were reduced and serum cholesterol decreased by 21-31% with the major change in high density lipoproteins. The findings suggest that cholesterol concentrations are not likely to be lowered in rats with portacaval anastomosis by enhanced lipoprotein catabolism.

Animals↗
PubMed1991

The influence of portacaval anastomosis on gonadal and anterior pituitary hormones in a rat model standardized for gender, food intake, and time after surgery.

Portacaval anastomosis causes delayed growth, decreased testes and liver weights, and elevated estradiol serum levels in male rats compared with sham-operated controls. Female rats treated with portacaval anastomosis grow at a normal rate despite changes in liver weight and estradiol levels similar to those observed in the male rats. This study examined the pituitary gonadal axis in both genders in this animal model. The rats receiving portacaval anastomosis were compared with both pair-fed and sham-operated control groups. Portacaval anastomosis decreased serum testosterone and increased estradiol in the male animals, while both testosterone and estradiol were increased in the females compared with gender-matched pair-fed and sham controls. Because pair feeding lowers male testosterone to a lesser extent, impaired nutrition may partially account for the decrease in the males treated with portacaval anastomosis. The ratio of estradiol to testosterone increased following anastomosis in male rats, but it was decreased in similarly treated females. Portacaval and anastomosis decreased luteinizing hormone without changing follicle-stimulating hormone in both male and female rats compared with sham-operated controls. Growth hormone was significantly decreased in male portacaval-treated rats compared with sham- and pair-fed animals. Increased insulin levels were found in both male and female pair-fed and portacaval anastomosis-treated animals. These data suggest that following portacaval anastomosis in rats, growth, serum testosterone, estradiol to testosterone ratios, and growth hormone are altered in a gender-specific manner with gender-independent changes in insulin and luteinizing hormone levels. These gender-specific effects may protect the portacaval anastomosis-treated female rat from growth retardation.

Animals↗
PubMed1990

Hepatic haemodynamic changes after portacaval anastomosis in normal, cirrhotic and chronic prehepatic portally hypertensive rats.

Radioactive microspheres were used to determine the hepatic haemodynamic response to portacaval anastomosis in normal, cirrhotic and chronic prehepatic portally hypertensive rats 20 days after operation, and in normal rats 2 months after operation. After 20 days portacaval anastomosis caused a decrease in liver mass only in normal and cirrhotic animals, whereas hepatic arterial blood flow per unit of mass increased in normal (+488 per cent), cirrhotic (+191 per cent) and prehepatic portally hypertensive rats (+133 per cent). Despite these facts, animals with portacaval anastomosis showed a reduced hepatic total perfusion (arterial plus portal inflow) per unit of mass with respect to controls in normal (-53 per cent) and cirrhotic rats (-68 per cent), but not in those with prehepatic portal hypertension. Comparing studies carried out at 2 months with those performed 20 days after portacaval anastomosis in normal rats, some recovery of liver mass and total liver blood flow was observed. In conclusion, portacaval anastomosis produced a limited increase in hepatic arterial blood flow which was unable to preserve liver mass and its total perfusion in normal and cirrhotic animals. In contrast, portacaval anastomosis did not significantly alter liver mass or its perfusion in animals with chronic prehepatic portal hypertension, as both values were previously diminished in controls. Thus, the risk of liver failure after portacaval anastomosis is higher in normal and cirrhotic rats than in those with chronic prehepatic portal hypertension.

Animals↗
PubMed1985

[Behavior of urinary magnesium in comparison with urinary calcium and oxaluria in rats subjected to portacaval anastomosis].

Rats with a portacaval anastomosis are known to be susceptible to develop uric acid stones. The present studies were undertaken to investigate urinary Mg, Ca and oxalate excretion in such rats. We found that their Mg excretion was doubled, Ca excretion tripled, and oxaluria somewhat decreased. The Ca crystallization attributed to the increased Ca2+ in the urine is, therefore, somewhat held in check by the increased presence of Mg in the urine and by decreased oxalates.

Animals↗
PubMed1978

Blood-brain neutral amino acid transport activity is increased after portacaval anastomosis.

In rats after portacaval anastomosis (an animal model of chronic liver disease), transport of tryptophan and other members of the large neutral amino acid group from blood to brain was markedly enhanced. Increased transport activity was apparently restricted to the neutral amino acid transport system, since brain uptake of glucose, inulin, and tyramine was unaffected while blood-brain arginine transport was significantly reduced. These results strikingly confirm the hypothesis that carrier-mediated blood-brain transport is the limiting factor determining the availability of the neutral amino acids to the brain. The encephalopathy associated with cirrhosis may be the result of abnormal neurotransmitter metabolism and neurotransmission secondary to increased neutral amino acid transport activity and an increased brain content of members of the neutral amino acid group.

Amino Acids↗
PubMed1985

Cholesterol metabolism in lean and obese Zucker rats: effects of portacaval anastomosis.

The effects of portacaval anastomosis (PCA) on cholesterol biodynamics of male adult (fa/fa) Zucker rats and their lean littermates were studied with an isotopic equilibrium method. Animals were fed with a sucrose-rich semi-purified diet. Obese rats were hypercholesterolemic (2.03 +/- 0.14 vs 1.06 +/- 0.7 mg/ml), had a cholesterol-enriched liver (135.3 +/- 14.5 vs 40.0 +/- 2.6 mg/liver) and accumulated cholesterol in body pools. However no difference in the rates of cholesterol absorption, synthesis, fecal elimination or transformation into bile acids distinguished obese from lean Zucker rats. In both lean and obese rats, PCA decreased cholesterolemia by about 28 per cent and liver weight by 40 per cent while the total cholesterol content of the liver was not affected. Input of synthesized cholesterol (internal secretion) was strikingly decreased by the shunt (from 13.2 +/- 0.6 and 12.6 +/- 0.7 mg/day/rat before PCA, to 8.9 +/- 0.8 and 8.6 +/- 1.0 mg/day/rat after PCA) in lean and obese rats respectively. A similar decrease was observed in the cholesterol transformation into bile acids. Since the activity of the gut for cholesterol synthesis, as shown by the fecal external secretion (cholesterol synthesized by the gut and directly eliminated in the gut and feces) was probably not modified, the reduction of internal secretion induced by PCA resulted from decreased hepatic cholesterogenesis. It is suggested that this decrease may be one of the factors involved in the lowering effect of PCA on plasma cholesterol level.

Animals↗
PubMed1991

Postoperative course after portacaval anastomosis in rats is determined by the portacaval pressure gradient.

Variability in experimental results have led to criticism regarding the validity of the rat after portacaval anastomosis (PCA) as a model of changes induced by portal-systemic shunting (PSS). A nonsuture technique using cyanoacrylate glue has been reported to yield a better experimental preparation. To investigate if variations in splanchnic hemodynamics could explain different outcomes after the procedure, male rats received either an end-to-side PCA or sham operations (16 rats each). The PCA was constructed using the "suture" or "glue" technique (8 rats each). Beginning on postoperative day 24 under methoxyflurane and ketamine anesthesia, pressures were recorded from the portal vein, inferior vena cava, and femoral artery. Blood flow to the splanchnic organs and the percent PSS were assessed using the microsphere technique. The rate of delivery of NH3 from the portal vein to the systemic circulation and the concentration of glutamine in the cerebrospinal fluid were determined. In PCA rats, weight gain was significantly impaired, and all animals had evidence of liver atrophy (in both suture and glue groups) when compared with sham animals; a trend toward greater weight gain was seen in glue rats. Portal vein inflow, PSS, NH3 delivery, and CSF glutamine were significantly increased in both PCA-suture and PCA-glue animals compared with sham rats, although no significant differences were seen between the two PCA techniques. When PCA rats from either technique were grouped according to the pressure gradient between portal vein and inferior vena cava, striking differences between animals were now evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1984

Dietary influences on the hepatic mixed-function oxidase system in the rat after portacaval anastomosis.

Studies were undertaken to determine the influence of diet on the hepatic mixed-function oxidase system in rats after portacaval anastomosis. Male rats fed either a cereal-based or purified diet underwent portacaval anastomosis. Weight gain after surgery was highly dependent on the diet. Because rats fed the cereal-based diet weighed 50% less at 4-5 wk after portacaval shunt surgery than unoperated controls fed the same diet, pair-fed unoperated controls were also studied. Rats fed the purified diet grew normally after shunting and therefore studies with this diet did not require pair-fed controls. Shunted rats fed the cereal-based diet had lower liver weights, hepatic microsomal protein concentrations, ethylmorphine N-demethylase, aniline hydroxylase, and cytochromes P450 and b5 when compared with corresponding values in unoperated controls fed the same diet ad libitum; comparisons with pair-fed controls indicated that decreased intake of the cereal-based diet could account for part but not all of the changes seen after portacaval anastomosis. It was shown in rats fed the purified diet that sham operation had no effect on the mixed-function oxidase system, whereas portacaval anastomosis resulted in reduced liver weight, microsomal protein, ethylmorphine N-demethylase, aniline hydroxylase, and cytochrome P450. In comparing shunted rats fed the two types of diet, in contrast with the effects of these diets in normal rats, these hepatic microsomal mixed-function oxidase system components were generally lower in the shunted rats fed the cereal diet. It is concluded that although decreased mixed-function oxidase activity occurs after portacaval anastomosis in the rat, the diet can have an additional substantial influence. Dietary influences on drug oxidations may be an important consideration in drug therapy after portacaval anastomosis.

Aniline Hydroxylase↗
PubMedDate not supplied

Improvements in host immunity by partially purified interleukin 1 in rats with portacaval anastomosis and splenectomy.

Despite the high incidence and severity of bacterial infections in individuals with chronic liver disease, the relative role of host immunity and the effects of immune stimulants have not been fully investigated. To study the role of the liver and spleen in reticuloendothelial system (RES) function and the host response to infection following portacaval anastomosis, 107 Sprague Dawley CD rats received a portacaval anastomosis either with or without an additional splenectomy, or a sham procedure. Animals that had undergone portacaval anastomosis and splenectomy were also administered a nonspecific host immune stimulant, interleukin 1, or saline and the effect on blood bacterial clearance and organ uptake examined. Three to four weeks following surgery, animals that received a portacaval anastomosis had a decreased ability to clear 59Fe-labeled Pseudomonas aeruginosa from the blood and an increased uptake of bacteria in the spleen (p less than 0.01) when compared to sham-treated animals. Rats that received a portacaval anastomosis and splenectomy showed further decreases in blood clearance and increased sequestration of bacteria in the liver (p less than 0.01). Rats with a portacaval anastomosis and splenectomy that received interleukin 1 treatment prior to Pseudomonas bacteremia showed significantly improved blood bacteria clearance (p less than 0.05) and a reduced bacterial sequestration in the liver (p less than 0.001) when compared to similar animals receiving saline. These findings suggest that portacaval anastomosis and splenectomy result in impaired immune function as reflected by blood bacteria clearance and changes in organ sequestration of bacteria. Secondly, pretreatment of those immunocompromised animals with interleukin 1 improves immune function.

Animals↗
PubMed2001

Altered content and modulation of soluble guanylate cyclase in the cerebellum of rats with portacaval anastomosis.

It is shown that the glutamate-NO-cGMP pathway is impaired in cerebellum of rats with portacaval anastomosis in vivo as assessed by in vivo brain microdialysis in freely moving rats. NMDA-induced increase in extracellular cGMP in the cerebellum was significantly reduced (by 27%) in rats with portacaval anastomosis. Activation of soluble guanylate cyclase by the NO-generating agent S-nitroso-N-acetyl-penicillamine and by the NO-independent activator YC-1 was also significantly reduced (by 35-40%), indicating that portacaval anastomosis leads to remarkable alterations in the modulation of guanylate cyclase in cerebellum. Moreover, the content of soluble guanylate cyclase was increased ca. two-fold in the cerebellum of rats with portacaval anastomosis. Activation of soluble guanylate cyclase by NO was higher in lymphocytes isolated from rats with portacaval anastomosis (3.3-fold) than in lymphocytes from control rats (2.1-fold). The results reported show that the content and modulation of soluble guanylate cyclase are altered in brain of rats with hepatic failure, resulting in altered function of the glutamate-NO-cGMP pathway in the rat in vivo. This may lead to alterations in cerebral processes such as intercellular communication, circadian rhythms, including the sleep-waking cycle, long-term potentiation, and some forms of learning and memory.

Animals↗
PubMed1987

'Cuffed' portacaval anastomosis in rat.

Preparation of portacaval anastomosis (PCA) in patients suffering from portal hypertension has been an accepted procedure for reducing portal pressure. Recently, fashioning of mesocaval anastomosis has got preference. In the era of portacaval anastomoses numerous experimental works were concerned with the technique of performing them. During these experiments it was revealed that PCA produces considerable changes both in the metabolism and the circulation of the liver. Fischer et al. state that, following PCA, the weight of the liver decreased, on an average by 55%, as compared to the controls. Ossenberg et al. observed that after PCA liver perfusion was reduced by about 55-65%. Rubin et al. demonstrated that the hepatic cytochrome P 450 content was significantly decreased and the function of the microsomal drug metabolizing enzymes markedly altered subsequent to PCA. All these data indicated that, as a results of the bypassing of portal inflow from the liver, PCA significantly influences liver function and the intervention in experimental animals, i.e. rats, can be used as a model for chronic hepatic insufficiency.

Animals↗