Plasma levels of zinc, copper, magnesium and calcium in rats after partial hepatectomy.
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Animals↗
Biomedical subjects
B Jeppsson
Publications and source records attributed to B Jeppsson.
Hepatic dearterialization in cancer: new perspectives.
Attempts have been made over the last 20 years, without notable success, to improve the prognosis of hepatic tumors by interfering with the blood supply from the hepatic artery. We review the background and history of this technique and offer a hypothesis as to its mechanism via free radicals. The ways in which this modality of treatment could be improved to optimize damage to the tumour are outlined.
Antineoplastic Agents↗
Hepatotrophic effect of portal blood during hepatic arterial recirculation.
Portal branch ligation (PBL) is known to induce a rapid and progressive atrophy in the liver parenchyma without portal blood flow and compensatory hyperplasia in the segments receiving the whole portal flow. In this study, the hepatotrophic effect of portal blood was studied in rats with PBL and after this procedure was combined with different portosystemic shunts. After 2 weeks, the most severe atrophy was found in ligated lobes of rats with PBL alone. In shunted animals, the atrophy was significantly inhibited and in relation to the magnitude of portal flow bypassed the liver. This suggests that in shunted rats, the portal-bone hepatotrophic factors undergo systemic recirculation and affect the liver by way of the hepatic artery. Simultaneously, in PBL + shunt rats, the rate of atrophy normally induced by a shunt was also dependent on the amount of portal blood available to this part of the liver. By a balance between these 2 processes, the total liver mass was maintained at the level found in sham PBL + shunt control rats.
Animals↗
Major liver resection: perioperative course and management.
This report investigates the perioperative course in 81 consecutive major liver resections, performed mainly because of primary liver cancer or colorectal liver secondaries. The liver was resected transabdominally with or without prior ligation of hilar structures. Intravenous nutrition consisted of 10% dextrose alone and was started preoperatively. Albumin or plasma was used rarely and only in conjunction with massive intraoperative transfusion of blood. Major complications, including four operative deaths (4.9%), consisted of bleeding and/or infection in eight (10%) patients and overt liver failure in two patients (2%) and occurred only after right and extended right lobectomies. Intraoperative blood loss was significantly larger in patients with postoperative complications than in patients with an uneventful postoperative course. The direct parenchymal approach was associated with a shorter operative time and an unchanged intraoperative bleeding. Coagulopathy and hypoalbuminemia did not cause any problems. Blood glucose levels were stable, and no patient suffered from hypoglycemia. It is concluded that major liver resection should be based on prevention of intraoperative bleeding and that preresection ligation of hilar structures offers no advantage in this respect. Infusion of hypocaloric glucose solutions should be started the day before operation, and routine administration of other nutrients does not seem necessary.
Adenoma, Bile Duct↗
Portal branch ligation in the rat. Reevaluation of a model.
The effects of portal occlusion on the liver have been differently reported in different studies. The authors therefore reevaluated a model of portal branch ligation (PBL) in the rat. Histologic appearance, DNA synthetic activity, labeling count, and mitotic index were serially evaluated in both ligated and nonligated parts of the liver after interruption of the portal flow to one fourth, one third, and two thirds of the liver mass. The authors confirmed the presence of compensatory hyperplasia induced in the nonligated liver lobe(s) by PBL, and its intensity was roughly proportional to the amount of liver tissue devoid of portal perfusion. Portal-deprived liver tissue underwent a rapid and progressive atrophy, and, by the end of the first week, the weight of this part had decreased 10-fold. By a balance between atrophy and compensatory growth, the total liver weight was maintained at the level of sham-operated animals throughout the experiment. PBL invariably resulted in early centrilobular necrosis, which occupied 15-24% of the ligated lobe(s). However, already after 4 days it was almost totally resorbed and did not appear de novo. PBL was not followed by local collateralization.
Animals↗
Brain monoamine metabolism and behavior in portacaval-shunted rats.
Animals with a portacaval shunt exhibit several biochemical abnormalities in plasma and brain similar to patients with portal-systemic encephalopathy, i.e., hyperammonemia, amino acid imbalance, and neurotransmitter disturbances. We investigated behavior and brain monoamine metabolism in operated, sham-operated, and nonoperated rats 1 day and 2, 4, and 6 weeks after operation. In order to quantitate the turnover in the brain indoleamine and catecholamine systems, 5-hydroxytryptophan (5-HTP) and dihydroxyphenylalanine were measured after decarboxylase inhibition with NSD 1015. The brains were dissected into five regions. All rats with the shunt had high plasma ammonia concentrations. Behavioral tests revealed a reduction in spontaneous locomotion 2, 4, and 6 weeks after portacaval shunt and reduced exploratory behavior compared with control rats. These changes coincided with profound alterations of the indoleaminergic system. As early as 1 day after surgery, rats with the shunt showed a marked increase in the accumulation of 5-HTP in all brain regions, indicating an enhanced tryptophan hydroxylase activity. The changes in indoleamine synthesis were most profound in the cortex and the midbrain. Only minor alterations of the catecholaminergic system could be detected. The alterations in behavior and indoleamine neurotransmitter metabolism may be pathophysiologically interrelated and may serve as the basis for experimental studies of portal-systemic encephalopathy.
Animals↗
Stimulation of DNA synthesis in the rat liver during compensatory renal growth.
The stimulatory effect of a growing kidney upon the liver was studied in rats with renoportal anastomosis (RPA) and contralateral nephrectomy. DNA synthesis, mitotic activity, and index of growth in the renoprival kidneys were independent of the shunt. Hepatic uptake of [Me-3H]thymidine was increased in both RPA-nephrectomized and sham-RPA-nephrectomized rats; however, in the latter group of animals the response was significantly greater. Results of the study suggest that stimulatory substance of renal origin is carried in the venous blood of a growing kidney. A nonspecific interaction between the renotropic and portal-borne hepatotrophic factors seemed to be responsible for stimulation of hepatic DNA synthesis. The study supports the view that mechanisms humoral in nature but not common promote reparative growth in different organs such as the liver and kidney.
Animals↗
Alterations in trace element and plasma amino-acid profile in experimental gram-negative septicaemia.
Infection can produce changes in the levels of trace metals such as copper, iron and zinc and several amino acids. These trace metals are involved in many metabolic reactions as well as in the host defence response. In the present study we have induced septicaemia in male Sprague-Dawley rats. The rats were made septic by surgical insertion of a gelatine capsule containing known amounts of E. coli (1.25 x 10(7) bact/ml) and Bacteroides fragiles (2.5 x 10(7) bact/ml) along with sterile rat faeces as an adjuvant (50% vol/vol), and barium sulphate (10% weight/weight) as an irritant into the abdomen. Blood samples were collected at 36, 60 and 72 h to study alterations in the pattern of copper, zinc, calcium and magnesium and plasma amino acids. Liver samples were taken after sacrifice at 72 h for inorganic element analysis. Sepsis produced a significant increase in copper and magnesium and a significant decrease in zinc and calcium levels of plasma. Trace element content of the livers the septic rats did not differ appreciably from control rats. Septic rats also had a lowered concentration of branched chain amino acids. These changes especially those of copper and zinc could be expected to have a role in the progress of the disease. The changes observed in the present study might be caused through the release of Interleukin-I or related substances from the phagocytic cells.
Journal Article↗
Tumor growth in liver atrophy and growth. An experimental study in rats.
Despite vast knowledge on liver regeneration, little is known about the effect of active liver atrophy and regeneration on tumor growth. Ligation of a branch of the portal vein to the one or two anterior lobes was performed in inbred Wistar rats. This induces acute atrophy of the anterior and regeneration of the other lobes. During the same operation a tumor cell suspension (NGW1--adenocarcinoma) was inoculated in liver lobes undergoing atrophy and regeneration. Tumor volume and weight were measured and the histologic appearance was assessed. During the early and active phases the tumor growth was significantly accelerated in regenerating lobes and partially inhibited in rapidly atrophied segments. After the regeneration and atrophy was completed the normal pattern of growth was re-established in both parts of the liver. The results suggest that tumor growth is affected in proportion to regenerative response. They further suggest that portal branch ligation is of limited value in surgical palliation of liver tumors. The risk for further induction of growth of clinically undetected tumor foci in the remaining liver tissue appears to be small, although a significant, but short-lasting, stimulatory response was found.
Animals↗
Relationship of brain glutamine and brain neutral amino acid concentrations after portacaval anastomosis in rats.
Evidence from several sources suggest that blood-brain transport of the large neutral amino acids (NAA) is abnormal in animals with a portacaval anastomosis (PCA) and in patients with liver cirrhosis and portal-systemic shunting and encephalopathy, but the underlying mechanisms are unknown. After PCA, the concentration of glutamine (Gln) in brain is markedly increased as a by-product of cerebral ammonia detoxification, and the rate of efflux of Gln from brain is also increased. The following studies were undertaken to clarify the relationships among plasma and brain concentrations of NAA after PCA in rats and to examine the relationship of brain Gln concentration to plasma and brain NAA concentrations. After PCA plasma phenylalanine, tyrosine and histidine were elevated and leucine, isoleucine and valine were lowered. In brain, phenylalanine, tyrosine, histidine and methionine were markedly elevated after PCA and their concentrations in brain far exceeded the concentrations in plasma. Analyses of single, partial and multiple correlations of plasma NAA ratios expressed as plasma competitor function (PCF), brain NAA and brain Gln showed significant correlations between PCF nd brain NAA in shunted rats. A better correlation was found between brain NAA and brain Gln. Correlation coefficients obtained from multiple correlation analysis equalled or exceeded those obtained in the partial correlation or in the single correlation, suggesting that the effects of PCF and brain Gln on brain NAA were separate and additive. Gln was shown to compete with other NAA for blood brain transport by inhibiting brain 14C phenylalanine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Standardized intraabdominal abscess formation with generalized sepsis: pathophysiology in the rat.
Gelatine capsules containing Escherichia coli and Bacteroides fragilis in a standardized mixture with rat colonic content and barium sulfate were implanted intraabdominally into rats. Capsules of 0.75 g gave approximately 50% mortality whereas 0.35 and 1.10 g caused no or 100% mortality, respectively. In subsequent experiments, using the 0.75 g capsule, all animals became ill with signs of tachypnea, piloerection, low physical activity and hypersecretion of saliva 6-8 h after the implantation. The animals reduced their water and food intake substantially and the body weight decreased. A significant reduction in blood pressure, glucose and leukocyte and platelet counts was found 12 h after challenge. Blood cultures obtained at 12, 24, 48 and 60 h all grew E. coli but none B. fragilis. Succumbed animals revealed diffuse peritonitis with growth of E. coli and B. fragilis at autopsy, whereas surviving animals showed abscess formation at investigation on day 8 after challenge. It was concluded that the model closely resembled intraabdominal abscess formation with sepsis in man.
Abdomen↗
Increased bleeding during liver resection after sympathetic block in normal rats.
The effect of sympathetic block on hemostasis after standardized liver resection was studied in the rat. Sympathetic block was undertaken by paravertebral block or surgical sympathectomy. Blood loss was significantly increased, but the bleeding time was not prolonged after paravertebral block. Surgical sympathectomy also increased blood loss as compared to controls, but there was no difference when compared with sham operation. Adenosine diphosphate and collagen induced platelet aggregation was not inhibited in all animals as compared to controls. The results indicate that primary hemostasis was not seriously affected, but that hepatic blood flow was augmented after sympathetic block.
Anesthesia, Epidural↗
Acute portal vein stenosis. An experimental study on portal circulation and hepatosplenic function.
Portal hypertension was mechanically induced in rats by acute constriction of the portal vein. Using a new "button" technique, a stricture 0.9 mm in diameter was found to be compatible with life in more than 90% of the rats. Angiographic and anatomic studies of portosystemic collaterals confirmed observations in earlier experiments. Oesophageal varices were not seen, despite sustained elevation of portal venous pressure during the four weeks following induction of portal hypertension. Development of paraportal veins bridging the obstacle is suggested to be responsible for maintenance of normal liver structure and for recovery from the transient hepatic dysfunction. Increase of phagocytosis in the germinal centres of the enlarged spleens was found after four weeks, suggesting immunologic changes caused by portal hypertension and/or portosystemic shunt circulation.
Animals↗
Hepatotrophic factors in liver growth and atrophy.
The hepatotrophic effect of portal blood was studied in rats with portal branch ligation (PBL) simultaneously subjected to mesocaval shunt or total hepatic arterialization. A direct supply of the nonligated liver lobes with pancreatic effluent did not improve DNA synthesis or mitotic response compared to arterialized rats, in which the portal-borne hepatotrophic factors reached the same lobes after systemic recirculation. A comparison with shunted but Sham-PBL rats showed that restorative capacity of the liver was not seriously impaired. In rats with PBL alone the lobes with portal occlusion showed extensive necrosis. In contrast, in PBL + shunt rats necrosis was significantly inhibited, indicating a hepatoprotective role of portal blood during hepatic arterial recirculation. Thus, the study suggests that quality of hepatic blood supply is of vital importance in maintenance of hepatocellular integrity. Hemodynamical factors seem to be of importance, but more in a sense of increased or decreased accessibility of humoral hepatotrophic factors in the blood.
Animals↗
Blood supply of experimental liver tumors after intraarterial embolization with gelfoam powder and absolute ethanol.
Twenty rats with implanted liver tumor were studied. Following baseline angiography, the hepatic artery was embolized with Gelfoam powder or ethanol (n = 12) while the controls (n = 8) did not undergo embolization. Postmortem Microfil perfusion was performed in all livers. Filling of tumor lakes from the portal vein was seen more often in embolized animals than in controls, indicating the potential role of the portal venous system in the supply of dearterialized hepatic tumors. We discuss the possible clinical implication of our results.
Animals↗
Methionine sulfoximine prevents the accumulation of large neutral amino acids in brain of hyperammonemic rats.
Accumulation of neutral amino acids in the brain due to altered transport across the blood-brain barrier appears to be a consequence of portal-systemic shunting and hyperammonemia. It has been suggested that high brain concentrations of glutamine, a product of cerebral ammonia detoxification, accelerates the transport of other neutral amino acids from blood to brain. To test this hypothesis, normal rats were infused with ammonium salts with or without pretreatment with L-methionine-dl-sulfoximine (MSO), an inhibitor of glutamine synthesis. Pretreatment with MSO prevented most ammonium salt-induced changes in the concentrations of the neutral amino acids in brain, suggesting that hyperammonemia alters the transport of neutral amino acids across the blood-brain barrier by causing the brain glutamine level to rise.
Amino Acids↗
Spontaneous motor activity increases after portacaval anastomosis in rats.
Spontaneous motor activity was monitored in rats at various times, up to 14 weeks, after portacaval anastomosis (PCA) or sham operation. Total 24 hour activity scores rose significantly after PCA and remained significantly higher than those of sham operated rats for twelve weeks. After PCA, activity during the twelve hour lighted period was greatly increased, whereas dark period activity was unchanged. Increased activity in the light period was found to be well correlated with the degree of elevation in brain concentrations of tryptophan, tyrosine, phenylalanine and glutamine. These results are consistent with previously reported EEG studies and suggest that motor-activity measurement may facilitate the correlation of biochemical changes with behaviour in rats with portal systemic shunting.
Amino Acids↗
Cytoprotective effect of 16,16-dimethyl prostaglandin (PGE2) on ischemic splanchnic injuries in the rat.
Cytoprotective effect of 16,16-dimethyl prostaglandin E2 (PGE2) was studied on splanchnic ischemia in rats. The superior mesenteric artery or the vascular pedicle to the isolated right hepatic lobe was occluded for 30 min, respectively, 1 or 2 h. Groups of rats were pretreated with PGE2 in a dose of 5 micrograms/kg b.w. 30 min before induction of ischemia. Ischemic damage was assessed by release of the lysosomal enzyme beta-glucuronidase and ALAT into circulation, the enzyme content in ischemic bowel and histology. Small bowel ischemia induced a marked enzyme release, a decrease of enzyme and protein content in the ischemic mucosa and typical histologic alterations. These findings were abolished in rats pretreated with PGE2. Occlusion of the vascular pedicle of the right hepatic lobe also caused enzyme release and histologic changes, but these were not affected by pretreatment with PGE2. PGE2 has a protective effect on small bowel ischemia and the observations support the concept that PGE2 may act by stabilization of cellular cytomembranes. No effect was observed on ischemic liver cell injury and this type of cell injury may be caused by other disturbances of cell function besides altered membrane function.
16,16-Dimethylprostaglandin E2↗