Intravenous ursodeoxycholic acid reduces cholestasis in parenterally fed newborn piglets

BACKGROUND & AIMS: Cholestasis complicates total parenteral nutrition (TPN) in preterm infants. Ursodeoxycholic acid (UDCA) is used for several cholestatic problems. The hypothesis of this study was that intravenous UDCA prevents TPN-induced cholestasis by (1) maintaining normal basal and stimulated bile flow, (2) altering bile composition, and (3) changing hepatocyte membrane composition and Na+,K(+)-adenosine triphosphatase (ATPase) activity. METHODS: Three groups of piglets were studied: group 1 received sow's milk, groups 2 and 3 received TPN, and group 3 also received 100 mumol.kg-1.day-1 UDCA intravenously. After 3 weeks, basal and stimulated bile flow were measured. Cholesterol, bile acids, phospholipids, and phospholipid fatty acids were analyzed in bile, and fluidity, phospholipid fatty acid composition, and Na+,K(+)-ATPase were analyzed in hepatocyte membranes. RESULTS: Bile acid secretion and basal and stimulated bile flow were similar in control and UDCA-treated animals but reduced to < 50% in the TPN group. Bile acid-dependent and -independent bile flow were lower in the TPN group. UDCA did not normalize abnormalities in TPN-induced bile composition. Sinusoidal but not canalicular membrane fluidity was different in TPN than in control and UDCA-treated animals. UDCA also increased Na+,K(+)-ATPase activity. Bile and membrane phospholipid fatty acids reflected dietary fatty acids. CONCLUSIONS: Intravenous UDCA improves bile flow and reduces bilirubin levels in the serum and liver in piglets with TPN-induced cholestasis.     

The effects of oral diazepam pretreatment on the biliary excretion of sulfobromophthalein in rats

Studies were performed with rats to examine the effects of single, as well as repetitive oral diazepam (DZP) pretreatment on biliary sulfobromophthalein (BSP) excretion rates and on bile flow parameters. One-hour pretreatment of male rats with 150 mg/kg of DZP resulted in about a one-third reduction in the peak biliary excretion rate of BSP (60 mg/kg, iv) and this was associated with a decrease in relative proportions of conjugated BSP in bile. The biliary excretion of preconjugated BSP was unaffected. BSP hepatic uptake and storage were apparently unaffected. In vitro DZP markedly inhibited BSP conjugating activity. In contrast to the above results, when BSP excretion was examined 1 h after the last of five daily oral doses of DZP (150 mg kg-1 day-1), no change in the peak elimination rate of this dye was evident. However, bile flow rates were higher in DZP-treated rats than in controls. When rats were examined 24 h after the last of five daily oral doses of DZP (150 mg/kg), the choleretic response persisted. Further studies showed that the repetitive DZP pretreatment enhanced the bile salt-independent mechanisms of bile formation.     

Protracted diarrhea and malnutrition in infancy: Changes in intestinal morphology and disaccharidase activities during treatment with total intravenous nutrition or oral elemental diets

Two therapeutic regimens were compared in 16 infants with protracted diarrhea and malnutrition. Eight patients were treated with total parenteral nutrition given via a central vein (group A); the remaining eight patients received a combination of dilute parenteral nutrients given in a peripheral vein plus continuous enteral feedings of an elemental diet (group B). All patients recovered although two infants in group B were switched to TPN treatment after a poor response to the elemental diet. Intestinal biopsies were performed: (1) before treatment; (2) after 2 to 3 weeks of TPN or elemental diet; and (3) after 2 to 3 weeks of Nutramigen feedings. Before treatment, all patients had atrophic changes in the jejunal epithelium and deficient disaccharidase and trypsin activities. The second biopsy showed morphologic recovery in all patients, incomplete recovery of lactase and trypsin in both treatment groups, and complete recovery of sucrase and maltase activities only in group B patients. The third biopsy showed normal morphology and complete recovery of all enzymes measured. The mean number of hospital days was 46 +/- 4.8 for group A and 34 +/- 1.6 for group B (p less than 0.05) suggesting that patients given enteral feedings early tended to have a more rapid return of intestinal function and of some intestinal enzymes.     

Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition

OBJECTIVE: The authors characterize the recovery of parenteral nutrition-induced changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract immunity with enteral nutrition and provide further information defining the effects of enteral feeding on mucosal immunity. SUMMARY BACKGROUND DATA: The small intestine plays a prominent role in development and maintenance of mucosal immunity, both intestinal and extraintestinal, primarily through immunoglobulin A (IgA)-mediated mechanisms. Prior research has shown that mice fed total parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible for IgA production, as well as impaired upper respiratory tract immunity to viral challenge of previously immunized animals. The recovery of TPN-induced changes in GALT and upper respiratory tract immunity after enteral refeeding is studied. METHODS: Male institute of Cancer Research mice received 5 days of TPN followed by 0 to 4 days of chow. Small intestinal GALT was characterized by flow cytometry. In a second experiment, animals were immunized intranasally with moused-adapted influenza virus. Three weeks later, one group received a 5-day course of TPN followed by enteral refeeding for 5 days. A second group received TPN alone. Both groups were challenged with intranasal virus and killed 40 hours postchallenge to determine viral shedding from the upper respiratory tract. RESULTS: Animals fed TPN only had significantly fewer GALT lymphocytes compared with those chow-fed control subjects. Peyer's patch counts increased after a single day of refeeding, returning to normal levels by 48 hours. Lamina propria counts remained significantly depressed after 24 hours of refeeding, but also returned to normal after 48 hours of refeeding. The T-cell and B-cell populations mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal only after 72 hours of refeeding. None of the 9 animals refed enterally for 5 days were positive for viral shedding, compared with 8 of 12 matched TPN-fed animals. CONCLUSIONS: Enteral refeeding after TPN is associated with rapid repletion of GALT cellularity, initially within Peyer's patches and subsequently within the lamina propria. Refeeding corrects the impairment of IgA-mediated upper respiratory tract antiviral immunity occurring with TPN administration. This work further enhances the authors' knowledge of the underlying immunologic differences influenced by routes of nutrition.     

Pentoxifylline and thalidomide fail to reduce hepatic steatosis during total parenteral nutrition and bowel rest in the rat

BACKGROUND: We suggested that the continuous translocation of endotoxin from Gram-negative bacterial overgrowth during bowel rest and total parenteral nutrition (TPN) causes the release of tumor necrosis factor (TNF), resulting in liver damage and hepatic dysfunction. Because TPN-induced hepatic steatosis was significantly reduced by the monoclonal antibodies against TNF, we attempted a more clinically applicable approach using pentoxifylline and thalidomide. METHODS: A control group (group I) fed rat chow and four groups of rats receiving TPN were studied. Group II received TPN only; group III, TPN and 100 mg/kg/d pentoxifylline; group IV, TPN and 200 mg/kg/d pentoxifylline; and group V, TPN and 5 mg/kg/d thalidomide. On day 7, total liver fat was determined. RESULTS: Bowel rest and TPN resulted in a significant (p < .0005) increase in liver fat content that was unaltered by either pentoxifylline or thalidomide. CONCLUSIONS: Our results show no role for pentoxifylline or thalidomide in reducing TPN-associated hepatic steatosis.     

The clinical significance of type 1 fiber predominance

Having recently demonstrated that taurine supplementation prevents total parenteral nutrition (TPN)-induced cholestasis, we chose to use this model to examine plasma membrane composition in relation to bile formation. Male guinea pigs received daily a mixture of glucose and of the amino acid solution Travasol with or without added taurine (1.2 mM). After 3 days, bile was collected and liver plasma membrane fractions enriched in sinusoidal lateral membrane and bile canalicular membrane domains were isolated. In animals receiving TPN alone, bile flow and biliary secretory rate of bile acid and bicarbonate decreased significantly compared with controls. Although membrane ATPases (Na+K+ and Mg+) were unchanged, TPN induced an increase in the lipid to protein ratio and a decrease of polyunsaturated fatty acids, in conjunction with a higher content of diene conjugates in sinusoidal lateral membrane fractions. Taurine corrected these changes and, in addition, reduced significantly the cholesterol to phospholipid ratio in both membrane fractions. The data show that changes in liver cell membranes occur in TPN-induced cholestasis and suggest that free radical injury may play a role. As taurine prevented cholestasis as well as membrane changes, it is suggested that taurine should be added to amino acid solutions used for parenteral nutrition.     

Tissue manganese concentrations and antioxidant enzyme activities in rats given total parenteral nutrition with and without supplemental manganese

BACKGROUND: Manganese is an essential but potentially toxic mineral. Parenteral administration of manganese via total parenteral nutrition (TPN) bypasses homeostatic mechanisms (intestinal absorption and presystemic hepatic elimination). Our objective in this study was to determine the effect of supplemental manganese in TPN solutions on manganese status in a rat model. METHODS: Male Sprague-Dawley rats underwent jugular catheterization and were given 61.0 +/- 0.4 g/d TPN solution providing 0.5 +/- 0.2 nmol manganese/g (Mn-; n = 6) or 16 +/- 3 nmol manganese/g (Mn+; n = 7) for 7 days. Reference rats (RF; n = 8) were fed a purified diet containing 1.3 mmol manganese/g. RESULTS: Liver manganese decreased in both TPN groups, but tibia, spleen, and pancreas manganese concentrations were greater in Mn+ rats than in Mn- or RF rats. Although no treatment differences were seen in heart or liver manganese superoxide dismutase activity, heart copper-zinc superoxide dismutase activity was lower in the Mn+ rats than in Mn- or RF rats (p < .05). Glutathione peroxidase activity was depressed in livers of both Mn- and Mn+ rats relative to RF rats (p < .0001), which was not due to selenium deficiency. CONCLUSIONS: Supplemental parenteral manganese is taken up to a greater extent by peripheral tissues than the liver. In this first report of antioxidant enzyme activities in animals maintained with TPN, we found that TPN as well as supplemental manganese can influence antioxidant enzyme activities. We conclude that it is generally unnecessary and potentially toxic to supplement TPN solutions with manganese during short-term usage.     

Clinical evaluation of anticancer effect of methionine-depleting total parenteral nutrition with 5-fluorouracil and/or mitomycin C

Methionine-depleting total parenteral nutrition (Met-deplete TPN), infusing AO-90 amino acid solution (lacking both L-methionine and L-cysteine) as a sole nitrogen source, showed synergistic effects with several antineoplastics including 5-fluorouracil (5-FU). In the recent multi-center, randomized, controlled study, advanced gastric cancer patients were randomly allocated to RT group and Control group. RT group received AO-90 amino acid solution, while Control group infused Amiparen (commercial methionine and cysteine containing amino acid solution) as protein source for 14 days' TPN with 5-FU and mitomycin C (MMC). The over all clinical response rate (PR+CR) in RT and Control groups were 26.3% and 8.1%, respectively, with significant statistical difference in both values at p = 0.015. Fourteen advanced gastric cancer patients allocated to RT and Control group randomly and received each amino acid as protein source for 7 days TPN with 5-FU administration. All cases were performed gastrectomy without waiting period, and resected material was examined the histological response. In the 7 cases of RT group, grade 2 was seen in 4 cases, grade 1-b in 1, grade 1-a in 1 and grade 0 in 1. In the 7 of Control, 3 cases were grade 1-a and the remaining 4 were grade 0. There were significant differences in both degree and incidence of the histological response at p = 0.016. A stage IV gastric cancer patient with marked liver metastasis received 2 times RT therapy with 5-FU and MMC for 14 days and undertaken gastrectomy after 22 day, waiting period. Resected gastric cancer showed grade 2 to 3 histological response, and the liver metastasis showed marked effect as PR to CR.     

The effect of intestinal transit time on bacterial translocation

Increase in intraluminal bacterial count, disruption of the mucosal integrity, changes in intestinal immunity and transit time are the factors involved in bacterial translocation. The relationship between intestinal transit time, intra luminal bacterial count and translocation rate were investigated in 40 Wistar-albino rats. The study was conducted in 4 groups with 10 animals in each. Group I (controls): saline + laboratory chow, Group II: saline + oral total parenteral nutrition (TPN) solution, Group III: morphine sulfate (MS) + oral TPN solution, Group IV: neostigmine bromide (NB) + oral TPN solution. Intestinal transit time was measured by using Indium111-labeled diethylene triamine pentaacetic acid (DTPA). It was prolonged in the MS-treated group and shortened in the NB-treated group (p < 0.01). The frequency of bacterial translocation was 60% in the oral TPN solution group, 100% in the MS-treated group, 20% in the NB-treated group and 10% in controls. Bacterial counts in duodenum, jejunum, ileum and caecum were significantly increased (p < 0.001) in the MS-treated group and decreased (p < 0.05) in the NB-treated group in comparison with the control group. In conclusion, the prolongation of intestinal transit time increased the intraluminal bacterial count and augmented bacterial translocation. The decrease in intestinal transit time had a converse effect.     

Pharmacokinetics and concentration-effect relationship after propofol infusion

This report summarizes data obtained via a mailed questionnaire from 129 Department of Veterans Affairs (VA) hospitals regarding current practices in the care of central venous catheters (CVCs) used for total parenteral nutrition (TPN). The size of VA hospitals' acute medical-surgical beds ranged from 14 to 1320 (median 168) beds. Over 6000 patients annually received CVCs for TPN. Hospitals reported using triple-lumen catheters most frequently as their CVC for TPN (80.3%). A povidone-iodine scrub was used to prepare the skin for CVC insertion by 72.6% of reporting hospitals. Sixty percent of hospitals used transparent polyurethane dressings. Care of CVCs varied among hospitals. Catheter-related infection and sepsis rates were within the national average, although < 50% of responding hospitals provided data on these outcomes. The results of this survey point to the need for a national standardized database relative to patients receiving TPN via a CVC.     

Delivery of total parenteral nutrition (TPN) via umbilical catheterization: development of a piglet model to investigate therapies to improve gastrointestinal structure and enzyme activity during TPN

Nutritional support of preterm infants by total parental nutrition (TPN) is common; however, TPN compromises intestinal structure and enzyme activity. Our goal was to develop a piglet model to assess the effect of limited enteral stimulation with formula and insulin-like growth factor-I (IGF-I) on intestinal morphology and enzyme activity. A nutritionally complete TPN solution was infused for 7 days and piglets were gavaged twice daily with 4 ml sterile water, formula, or formula containing 1,000 micrograms/l IGF-I. Litter mate piglets fed formula served as orally fed controls. On day 7, body weights and plasma hormone profiles of TPN and orally fed piglets were similar. However, intestinal weight, jejunal and ileal villus height and surface area, and mucosal lactase and sucrase activity of TPN piglets was reduced by approximately 50%. No effect of limited enteral stimulation or IGF-I was observed likely due to the small volume of formula administered enterally, which resulted in a low dose of IGF-I (4.3 micrograms IGF-I/kg/day).     

Studies on the regulation of food intake using rat total parenteral nutrition as a model

Total parenteral nutrition (TPN) is essential for maintaining the nutritional status of patients who are unable to eat sufficiently to meet their metabolic needs. However, TPN suppresses appetite and ultimately diminishes food intake. Theories concerning the role(s) of peripheral metabolites as signals, acting via the liver and the hypothalamus, for the metabolic control of food intake, have been put forward to explain the anorectic effect of TPN. In addition, it is postulated that changes in peripheral metabolites during TPN may be translated into changes in the levels of brain neurotransmitters known to decrease food intake. This review summarizes studies concerning the effect of TPN on food intake. These studies have involved: (1) characterizing the changes in feeding activity due to TPN; (2) investigating the involvement of the central nervous system; and (3) investigating the role of the periphery and its metabolites in the regulation of food intake during TPN. Some insight into the mechanism of action of TPN on food intake is provided.     

A compartmental model for hepatic transport of taurocholic acid in isolated perfused rat liver

In order to characterize the transport of bile acids through the liver and to study the influence of drugs on these processes, a kinetic model for hepatobiliary transport of taurocholic acid (TC) using the isolated perfused liver was developed. After the system was brought to a steady state by infusing TC at a constant rate, a tracer dose of 14C-TC was injected into the medium. The medium disappearance of 14C-TC followed a first-order kinetic with a single rate constant. The plot of the biliary secretion rate of radioactivity versus time revealed a curve composed of at least three exponential components. From the described results and the present knowledge of hepatobiliary transport of bile acids we proposed a three compartment model, composed of a perfusion medium compartment and two liver compartments. Parameters calculated from the model constants agreed well with model-independent estimations. The influence of bromosulfophthalein (BSP) on the kinetic parameters was studied to compare the result with the known effect of BSP on hepatic transport of taurocholic acid. BSP decreased the constant describing the fractional transfer of taurocholic acid from medium into the liver, which is in agreement with the inhibition of hepatic uptake of taurocholic acid by BSP. Thus a three compartment model may adequately define the hepatobiliary transport of taurocholic acid in the isolated perfused rat liver.     

Expression of the transcriptional regulator Egr-1 in experimental glomerulonephritis: requirement for mesangial cell proliferation

BACKGROUND/AIMS: The hepatic transport of bile salts can be regulated by changes in bile salt pool size and/or in the flux of bile salts through the liver. Prolonged bile salt pool depletion is associated with down-regulation of maximum taurocholate transport and decreased canalicular membrane specific bile salt binding sites. This study was undertaken to investigate: a) whether adaptive down-regulation of maximum hepatic bile salt transport occurs to the same extent for bile acids of different hydrophobicity; and b) the role of microtubule-dependent vesicular pathway in the adaptive changes of bile salt transport capacity. METHODS: Male rats were subjected to 24-h or 48-h external biliary diversion to induce bile salt pool depletion. Basal bile flow, bile salt secretion and lipid secretion, maximum secretory rate of three bile salts of different hydrophobicity (tauroursodeoxycholate, taurocholate and taurochenodeoxycholate) and changes in the biliary excretion of two markers of the microtubule-dependent vesicular pathway (horseradish peroxidase and polyethyleneglycol molecular weight-900) were measured in control and bile salt-depleted rats. Taurocholate-stimulated horseradish peroxidase biliary excretion was also assessed in order to define whether the restoration of bile salt flux across the hepatocytes increased the excretion of this marker in bile salt-depleted rats. RESULTS: The reduction in the maximum secretory rate of the three bile salts under study observed after prolonged biliary diversion was clearly related to their hydrophobicity, with greater reduction for taurochenodeoxycholate and smaller reduction for tauroursodeoxycholate, compared with taurocholate. The biliary excretion of vesicular transport markers was significantly reduced in bile salt-depleted rats. However, when stimulated by taurocholate, biliary excretion of horseradish peroxidase was similar to controls. CONCLUSIONS: The magnitude of the decrease of the hepatic bile salt maximum transport capacity seen after bile salt pool depletion is directly related to the hydrophobicity of the bile salt infused. A functionally depressed vesicular transport pathway appears to be also a contributing factor to this phenomenon.     

Accumulation of orally given cadmium in Long-Evans Cinnamon (LEC) rats with an inherently abnormal copper metabolism

An inherent defect of biliary Cu excretion and subsequent Cu deposition in the liver have been found in Long-Evans Cinnamon (LEC) rats, which are promising models of Wilson disease. LEC and Fischer rats were given water containing Cd (CdCl2) at a level of 5 ppm for 30 days. Regardless of drinking Cd water, LEC rats showed a very high concentration of Cu (200 to 250 microgram/g) and Cu-metallothionein (Cu-MT) (18 mg/g) in the liver. There was no difference of Cd accumulation in the liver between the two strains exposed to Cd (2.6 and 2.7 microgram/g in the Fischer and LEC groups, respectively). However, the renal Cd concentration was slightly but significantly higher in LEC rats (3.5 microgram/g) than in Fischer rats (2.0 microgram/g). The ratio of renal Cd contents to the sum of renal and hepatic Cd contents was significantly higher in LEC rats (0.25) than in Fischer rats (0.15). The serum Cd concentration in Cd-treated LEC rats increased threefold compared to Cd-treated Fischer rats. It seems likely that Cd from the liver is transported into the kidney in the form of Cd, Cu-MT. There was no difference in uptake of Cd in the hepatic MT fraction between the two strains. Although biliary Cu excretion in LEC rats was significantly lower than that in Fischer rats, reduced excretion of Cd into bile was not found in LEC rats. The gross amounts of Cu and Cu-MT influenced the accumulation of Cd in the kidney rather than in the liver when Cd was given orally at a low level to LEC rats. Our results suggest tht Cu and Cd do not share the same sites of hepatobiliary excretion in rats, although the main route of their excretion is via bile.     

Effect of lipid-free total parenteral nutrition on hepatic drug conjugation in rats

The effect of total parenteral nutrition (TPN) on drug conjugation in male Sprague-Dawley rats was examined using a nutrition solution composed of amino acids and glucose. The overall disposition of acetaminophen including the formation kinetics of the sulfate and glucuronide metabolites was used as an in vivo probe. Selected drug metabolizing enzyme activities also were examined in vitro. TPN, 200 kcal/kg/day, was administered by continuous i.v. infusion for 14 days and changes elicited were compared to control animals allowed free access to rat chow. TPN decreased the total clearance of acetaminophen by 34% and the formation clearance to acetaminophen sulfate by 47%. The formation clearance of acetaminophen to acetaminophen glucuronide was unaffected by TPN. Cytochrome P450 concentration and oxidative demethylase activity toward p-nitroanisole were decreased in parallel, 47 and 53%, respectively, and UDP-glucuronosyltransferase activity with p-nitrophenol and acetaminophen as the acceptor aglycones was decreased 44 and 25%, respectively in the animals receiving TPN. Sulfotransferase activity toward both p-nitrophenol and acetaminophen decreased 28% in animals receiving TPN vs. ad libitum rat chow. Administration of the parenteral nutrition solution as a continuous enteral infusion via a doudenal catheter slightly decreased p-nitroanisole demethylase activity (26%), but had no other significant effects on either cytochrome P450 concentration or on drug conjugating enzyme activities determined in vitro. These results show that parenteral nutrition administered i.v. depresses drug conjugation and suggest that alterations in both hepatic oxidative and conjugative biotransformation arising from total parenteral nutrition are largely attributable to bypassing the intestinal route for nutrient intake.     

Pediatric orthopedics at the Stuttgart Olga Hospital: the variety of disorders makes high demands on nursing]

Total parenteral nutrition (TPN) is associated with an increased incidence of bacterial translocation (BT) compared with enteral nutrition because of the disuse atrophy of the intestine. In this study, we assessed the effect of adding medium-chain triacylglycerols (MCT) to TPN for the prevention of mucosal atrophy in the intestine. Rats were subjected to either fat-free TPN, TPN with long-chain triacylglycerols (LCT), or TPN with MCT for 5 d and nutrition parameters were evaluated. In another set of rats receiving the same TPN regimen, 0.8 or 0.05 mg/kg endotoxin was administered on day 4. Survival was evaluated and BT to the mesenteric lymph nodes, liver, and systemic blood was measured 24 h later. The mucosal heights of the jejunum and ileum were evaluated concurrently. The survival rate was significantly improved in the MCT group (P < 0.05) at the endotoxin dose of 0.8 mg/kg. The nutrition condition presented by phospholipid, total cholesterol, and total ketone body levels was the best in the MCT group compared to the other groups. The intestinal villous height in the ileum was significantly greater in the MCT group. However, the improvement of BT in MCT group was not statistically significant. In this endotoxin-challenged rat model, survival rate was improved by the supplementation of MCT. This effect may be presented in some part by the improvement in nutrition condition and by the prevention of mucosal atrophy in the intestine.     

Hexachlorophene metabolism in rats: the hepatic route

The terminal elimination rate of radioactivity from the bile of bile-duct cannulated rats, that had received hexachlorophene-14C via the hepatic portal vein, had an apparent first-order half-life of about 10 hr. Tissue distribution studies in these rats indicated that 35-47% of the carbon-14 of the dose was eliminated through the bile within 24 hr. Significant amounts of radioactivity were also found in the liver and carcass at that time; the brain was the only tissue that did not consistently have much higher concentrations of carbon-14 than the blood. The rate limiting step in the disposition of hexachlorophene may be excretion into the bile. A bile-feeding technique demonstrated enterohepatic circulation.     

Nutritional support through percutaneous transhepatic internal drainage route in common bile duct cancer

A 69 year old female with a duodenal bulb obstruction due to direct invasion of common bile duct cancer who received total enteral nutrition through the route of percutaneous transhepatic internal drainage (PTID) was presented. The tip of PTID tube was placed over the duodeno-jejunal flexure. Jejunal infusion of all nutrients and the bile juice through this route kept her in good nutritional condition until the terminal stage of primary disease. This procedure did not cause the infection of the biliary system. Major problems, tube obstruction and diarrhoea, were easily resolved with the selection of an appropriate infusion schedule and nutrient concentration. We conclude that nutritional support through the PTID route is a beneficial means for compromised patients without laparotomy or hospitalization.     

Role of glutathione in hepatic bile formation during reperfusion after cold ischemia of the rat liver

BACKGROUND/AIMS: Liver reperfusion following cold ischemia is frequently associated with diminished bile flow in patients undergoing liver transplantation. Glutathione is a major determinant of bile-acid independent bile flow, and the effects of cold ischemia on biliary glutathione excretion are unknown. METHODS: We examined the effects of cold ischemia (University of Wisconsin solution (4 degrees C), 24 h) with subsequent reperfusion (100 min) on biliary glutathione excretion in a recirculating system. Since glutathione might represent an important antioxidant within the biliary tract and oxidative stress in the biliary tract during reperfusion could contribute to the pathogenesis of bile duct injury after liver transplantation, we also assessed bile duct morphology in reperfused livers of mutant TR- -rats, in whom biliary excretion of glutathione is already impaired. RESULTS: Hepatic bile formation was diminished in reperfused Wistar rat livers after cold ischemia. Biliary glutathione concentrations and output were significantly decreased and correlated with postischemic changes in bile secretion. An increased biliary oxidized glutathione/glutathione ratio, indicating oxidative stress, was detected only immediately after the onset of reperfusion. Basal bile flow rates in TR- -rat livers which were already markedly reduced in control-perfused livers, decreased further during the early but not the later reperfusion period. Reperfusion of both Wistar and TR- -rat livers was not associated with electron microscopic evidence of bile duct damage. CONCLUSIONS: We conclude that impaired biliary excretion of glutathione contributes to decreased bile flow after cold ischemia. The absence of biliary glutathione does not appear to promote ultrastructural evidence of bile duct injury during reperfusion in the isolated perfused rat liver.