Portacaval Shunted Rats Research Articles

Exaggerated consumption of saccharide solutions following experimental portacaval anastomosis in rats

Male Sprague-Dawley rats were subjected to end-to-side portacaval anastomosis and permitted to recover from the acute effects of this surgical procedure. Subsequently, portacaval-shunted rats consistently drank abnormally large quantities of 5% (W/V) solutions of glucose, fructose, and sucrose in 24-hr two-bottle tests with water present as the second fluid. The volume of glucose consumed was not altered when the concentration was increased from 5 to 10%. The pattern of preferences exhibited by the portacaval-shunted rats was similar to that of the sham-operated rats, even in three- to five-choice preference tests with several palatable fluids available simultaneously. However, no abnormally high consumption of either water- or quinine-adulterated sucrose solution was noted. Although exaggerated consumption of 0.1% sodium saccharin was not observed in the present study, subsequent unpublished research indicates that when portacaval-shunted rats are given a 0.06% sodium saccharin solution in a preference test, overconsumption relative to control rats occurs. Portacaval shunts were verified both by anatomical examination and by determination of hepatic and testicular atrophy at the conclusion of the investigation. The evidence suggests that over-responsiveness to a palatable taste underlies this phenomenon of exaggerated saccharide consumption.

Maze patrolling, open-field behavior and runway activity following experimental portacaval anastomosis in rats

Surgical construction of a portacaval shunt in patients with debilitating liver cirrhosis is frequently followed by the development of hepatic encephalopathy, characterized by severe cognitive and neuromuscular abnormalities. The rat with a portacaval anastomosis provides a heuristic animal model for the biochemical consequences of the portosystemic diversion of the circulation; the behavioral effects of such shunting were studied in the present investigation. The spontaneous behavior of male Sprague-Dawley rats with a chronic experimental portacaval anastomosis (end-to-side) was evaluated in a complex enclosed maze, an illuminated open field and an enclosed hexagonal runway. There was little evidence that portacaval shunted rats differed from sham operated rats in total activity, explored area, maze-center entry, or in either of two indexes of the efficiency of patrolling within a complex Dashiell-type maze over 13 successive days with three different maze configurations. Similarly, experimental and control rats did not differ in any of several responses assessed in an illuminated open field. However, rats with a portacaval shunt were hypoactive in a runway test given two months postsurgery. All experimental subjects were verified to have an open portacaval shunt and to have sustained significant liver atrophy. These results emphasize the subtle nature of the behavioral effects resulting from the surgical construction of a portacaval anastomosis in rats.

Effect of portacaval shunt on circulating free fatty acids and ketone bodies in rats

To ascertain whether portal diversion affects ketone body (KB) metabolism, fasting circulating levels of free fatty acids (FFA), acetoacetate (AcAc) and B-hydroxybutyrate (3-OH-B) were measured in portacaval shunted (PCS), sham-operated (S-O) and unoperated control (C) rats. In PCS animals blood KB concentration was clearly reduced when compared with S-O and C rats. Beta-hydroxybutyrate level was significantly lower in PCS rats, whereas AcAc concentration did not appear significantly modified in these animals. The hypothesis is proposed that hypoketonemia induced by portal diversion is due to reduced hepatic availability of fatty acids.

Hepatic ornithine aminotransferase in the rat after portacaval shunt.

L-Ornithine (2-oxoacid aminotransferase, OKT) has been determined in the livers of portacaval shunt (PCS) rats, submitted to different diets, influencing blood brain amino acid transport. OKT activity was not greatly influenced by PCS. An in vivo stimulatory effect by branched chain amino acids and arginine could not be observed or confirmed by amino acid analysis in liver tissue. However, after the addition of glucose to the diet, a significant drop of OKT activity occurred.

Cholesterol homeostasis in the rat with a portacaval anastomosis.

Studies were undertaken to determine the effect of portacaval anastomosis on cholesterol homeostasis in rats fed sucrose/lard under conditions of normal body growth. Four to 6 weeks after portacaval shunt surgery, we found decreases in plasma cholesterol and triglyceride concentrations, total liver weight, and hepatic microsomal protein concentration. Measurements oof hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) activity showed decreases in specific activity and total liver activity in portacaval shunt rats, but the enzyme diurnal rhythm remained. Decreased reductase activity in shunted rats was not due to an altered Km for D-HMG-COA, nor was an enzyme inhibitor found in the livers of the portacaval shunt animals. Sterol balance measurements in rats with shunts showed a 22% decrease in whole body cholesterol synthesis rate compared to controls. These metabolic studies, coupled with postmortem data, showed diminished bile acid synthesis, unchanged fecal neutral steroid excretion, and decreased net tissue accumulation of cholesterol during growth. The decreased whole body cholesterol synthesis rate ultimately led to a diminished total carcass cholesterol concentration in the rats with shunts.

Liver glycogen after portacaval shunt in rats

Theories to explain the metabolic effects of portacaval shunt (PCS) have frequently failed to take into account the sequelae of PCS-induced anorexia. In this study PCS rats, followed up to 42 days postoperatively, had a lower food intake than ad libitum-fed (ALC) controls and also lost 10% body wt compared to a 20% gain of ALC rats. Liver weight was significantly reduced in PCS rats compared to ALC rats, pair-fed sham-operated (S) and pair-fed normal control (PFC) rats. However, liver glycogen was equally reduced in all animals with reduced food intake (PCS, S, and PFC rats) compared to ALC rats. Plasma glucose was significantly lower in PCS rats and PCS rats had markedly elevated plasma glucagon and lower plasma insulin concentrations than ALC rats, with the result that they had a low insulin: glucagon molar ratio of 1.3:1 compared to 10.2:1 in the ALC rats. The pair-fed control groups had intermediate I:G ratios and plasma glucose concentrations, thus an inverse relationship between mean plasma glucose and mean I:G ratio for each group was found, suggesting that the blood glucose concentration was the primary event determining the I:G ratio for each group. These controlled experiments indicate that hepatic atrophy after PCS appears to be directly related to the shunting of portal blood away from the liver, while reduced liver glycogen is related to decreased food intake. Reduction in total body weight, relative hypoglycemia, and elevated I:G ratios appear to be due to a combination of factors.

Portacaval shunt in the rat: An animal model for evaluation of uricase activity

Summary End-to-side portacaval shunts were prepared in mature male rats and their uricemia was measured 7,14,21 and 30 days after the surgery. Due to hepatic uricase exclusion, a sustained increase in serum uric acid over preoperative levels was found between 7 and 21 days after operation. After that, uric acid levels slowly declined, probably as a consequence of the formation of adhesions between the portal circulation and the liver. The hyperuricemic portacaval-shunted rat is a suitable animal model for assaying exogenously administered uricase, and may help also in research studies in the area of hyperuricemic syndromes.

The effect of acute and subacute ammonia intoxication on regional cerebral acetylcholine levels in rats

Cerebral regional concentrations of acetylcholine (ACh) were measured in two acute (with or without portacaval shunt) and one subacute (average 3 days) models of ammonia-induced coma in rats. The animals were sacrificed by total-body or head-focused microwave irradiation which, respectively, decreases or essentially eliminates post mortem degradation of ACh. In the two acute models of coma, normal levels of ACh were found in cortex, midbrain, and brainstem. A small decrease in striatal ACh was noted in rats without portacaval shunt given ammonia, but not in the other acutely intoxicated group. By contrast, in the subacute model (portacaval shunted rat given ammoniated resin by gavage) ACh fell by 14, 20, 33 and 39%, respectively, in the cortex, corpus striatum, midbrain, and brainstem. It is suggested that this decrease in brain ACh is a concomitant finding and not the cause of the coma.

Enzymes of Ammonia Detoxication after Portacaval Shunt in the Rat

At high systemic blood concentrations ammonia may be partially deviated into the pathway of pyrimidine synthesis, as has been observed in different genetic defects of the urea cycle. The portacaval shunt (PCS) rat presents an animal model to study ammonia detoxication without an underlying enzyme defect in the urea cycle. Since ammonia may induce a deviation into the pyrimidine pathway by influencing enzymatic reactions involved in this pathway, the activity of carbamylphosphate synthetase and aspartate transcarbamylase in liver as well as the excretion of orotic acid in the urine were measured in rats 10, 20 and 30 days after PCS. The results suggest that in this experimental model ammonia may be channeled into the pyrimidine pathway leading to a stimulation of the first enzymatic step and to an increased excretion of orotic acid.

THE LIVER AND IMMUNE RESPONSES

Regional lymph node response in F1 hybrid rats in injection of parental adult liver cells was investigated. More than a 10-fold increase in node weight over the uninjected control node was observed on day 11 following injection of 60 X10(6) parental liver cells. The node weight gain was both dose and time dependent although 10 times more liver cells were required than the lymphocyte. Injection of either irradiated (600 rads) or cultured (30 days) liver cells did not reduce the reactivity. The liver cells prepared from 18-day-old fetuses, 70% hepatectomized or portacaval shunted rats were all shown to be reactive, the latter being far superior. This phenomenon is immunological since only parental (semi-allogeneic) but not syngeneic liver cells gave the reaction although a hybrid resistance cannot be denied. Possible mechanisms underlying this phenomenon are discussed.

Effects of antrectomy or porta‐caval shunting on the histamine‐storing endocrine‐like cells in oxyntic mucosa of rat stomach. A fluorescence histochemical, electron microscopic and chemical study.

1. The argyrophil (enterochromaffin-like) cells in the oxyntic gland area of the rat stomach contain histamine, which can be demonstrated fluorescence microscopically after exposure to gaseous OPT. After administration of L-dopa (or L-5-hydroxytryptophan), these cells produce and temporarily store dopamine (or 5-hydroxytryptamine), demonstrable by its characteristic formaldehyde-induced fluorescence. Ultrastructurally, the enterochromaffin-like cells, which have the appearance of polypeptide hormone-secreting cells, comprise two main cell types, the most predominant one having vesicular type granules (EGL cells), the second most predominant one having smaller, uniformly electron dense granules (A-like cells). 2. Rats were subjected to the following surgical treatments: antrectomy; porta-caval shunting; antrectomy+porta-caval shunting; or sham-operation. Three to eight weeks after surgery the histamine-storing cells (enterochromaffin-like cells) of the oxyntic mucosa were analysed by fluorescence histochemistry, light and (quantitative) electron microscopy, and fluorometric determination of amines. 3. After antrectomy, fluorescence histochemistry and silver staining revealed a reduced number of enterochromaffin-like cells. The histamine content in the oxyntic mucosa was reduced by about 50%. As in unoperated injection of pentagastrin seemed to mobilize histamine. Feeding or injection of insulin failed to do so in antrectomized as opposed to control rats. Ultrastructurally, the cytoplasmic granules of both endocrine-like cell types were less numerous than in the unoperated rats. The reduction in cell number and granularity was particularly conspicuous with regard to the EGL cells. 4. After porta-caval shunting the number of enterochromaffin-like cells increased markedly. Chemical determination revealed a twofold increase in the histamine concentration of the oxyntic mucosa. Feeding or injection of insulin or pentagastrin lowered the histamine concentration. As judged by electron microscopy, the proliferation of endocrine-like cells induced by porta-caval shunting was restricted to the ECL cell type. Besides occurring in greater number, these cells were larger than those in unoperated controls, and their cytoplasm was densely packed with granules that were increased in size. 5. Following antrectomy of the porta-caval shunted rats the number of enterochromaffin-like cells and the oxyntic histamine concentration was reduced. 6. The results support the idea that gastrin exerts trophic as well as excitatory effects on oxyntic endocrine-like cells.

The Effects of Nutritional and Hormonal Factors on the Fatty Acid Synthetase Level of Rat Liver

Abstract The rise in fatty acid synthesizing capacity of the liver which is observed on realimentation of fasting rats with a fat-free diet has been studied. The rise to supranormal levels has been shown unequivocally to be the result of adaptive enzyme synthesis. Proof of this was obtained through the demonstration that 14C-leucine is readily incorporated in vivo into the purified fatty acid synthetase complex formed during refeeding. In addition, measurements of the absolute levels of the enzyme in the livers of fasting and refed rats showed drastic changes in the content of this protein complex with changes in nutritional status. Similarly, alloxan diabetic and portacaval-shunted rats exhibited lowered levels of fatty acid synthetase in liver; and insulin treatment of alloxan diabetic animals caused a return of the level of this enzyme toward the normal range. The characteristics of the fatty acid synthetase isolated from the livers of rats refed for varying periods of time after fasting have been investigated. Differences in homogeneity and variation in specific enzyme activity of these preparations were found which correlated with the length of time of refeeding. The significance of these variations is discussed.

Effect of alloxan and portacaval shunt on the synthesis of fatty acids and sterols by rat liver

Experiments are presented which show the diminished capability with time of rat liver homogenates to synthesize nonsaponifiable compounds from mevalonic-2- 14C acid and fatty acids from acetyl-1- 14C-CoA and malonyl-2- 14C-CoA after induction of diabetes by alloxan injection. Insulin treatment partially repairs this defect. Portacaval shunted rats were also used to show a similar decline with time of lipogenesis after the shunting operation. This decreased production is not due to activators or inhibitors present in the liver homogenate, nor is it due to a limiting supply of NADPH; the suggestion is made that it reflects a decreased level of enzymes concerned with the biosynthesis of fatty acids and nonsaponifiable compounds in the liver.