Search

Dienoic eicosanoids derived from phospholipid arachidonic acid (AA) in lung and liver macrophages promote leukosequestration, thrombosis, and tissue injury. Current enteral diets (diet A) are enriched with linoleic acid (LA), a precursor of AA. Novel diets low in LA and containing eicosapentaenoic acid (EPA) and y-linolenic acid (GLA) foster formation of less inflammatory eicosanoids. The study objective was to assess the rapidity and extent of LA and AA displacement in vivo from alveolar macrophage (AMO, lung, and liver Kupffer and endothelial (KE) cell phospholipids in rats fed enterally with diets enriched with 5.3% (by wt) EPA and either 1.2% or 4.6% GLA (diets B and C, respectively). After surgical placement of catheters, the rats were fed enterally and co-infused intravenously with either endotoxin or vehicle continuously for 3 or 6 d. Rats given either diet B or C had significantly lower (P < 0.01) relative percentages of AA and LA within the AM[phi], lung, and KE cell phospholipids, and concomitantly higher percentages of EPA compared with rats infused with diet A after 3 d of enteral feeding irrespective of endotoxin co-infusion. Incorporation of dihomo-[gamma]-linolenic acid (DHGLA), the metabolite of GLA, into lung and KE phospholipids was significant in rats given diet C. Most of the changes in fatty acid composition occurred by day 3. The polyunsaturated fatty acid composition of AM[phi], lung, and KE cell phospholipids can be rapidly modified by continuous short-term enteral feeding with EPA- and GLA-enriched diets irrespective of concurrent endotoxemia.

Therapeutic modalities that downregulate macrophage and endothelial production of eicosanoid mediators by displacing membrane arachidonic acid (20:4[omega]6) may benefit patients at increased risk of septic complications. The objective of this study in rats was to assess the incorporation of fish or olive oil fatty acids into hepatic Kupffer and endothelial (K&E) cell phospholipids after 4 d of continuous enteral feeding during endotoxemia. Either endotoxin (ETX) (0.5-1 [mg.sup.-1][multiplied by][kg.sup.-1][multiplied by][day. or vehicle was infused intravenously during the last 72 h. Dietary fish and olive oil fatty acids were rapidly incorporated into both K&E and plasma phospholipids irrespective of ETX cotreatment. Rats infused with the fish oil-enriched diet had a significantly lower relative percent of both K&E linoleic acid (18:2[omega]6) and 20:4[omega]6, whereas rats infused with the olive oil-enriched diet only had a lower relative percent of 18:2[omega]6 compared with control rats receiving corn oil. Provision of specific dietary lipids by continuous enteral infusion may prove efficacious for the rapid modulation of hepatic sinusoidal cell membrane fatty acids under either normal or endotoxemic conditions. Am J Clin Nutr 1993;57:643-9.

The study objective was to assess hepatic utilization of exogenous adenosine or adenine to enhance ATP recovery in rat liver after cold ischemia. ATP was measured noninvasively by [P.sup.31] nuclear magnetic resonance (NMR) in perfused livers before and after 18 h of cold ischemia. The hepatocellular concentration of ATP during the initial postischemic reperfusion without adenosine or adenine coinfusion was 60% of that in fresh liver. The ATP increased significantly (P < 0.001) to 139% and 82% of baseline in postischemic livers coinfused for 90 min with adenosine or adenine final concentration, 1 mmol/L), respectively. Less than 0.5% of the excess adenosine was catabolized to uric acid. In conclusion, adenosine and, to a lesser extent, adenine are salvaged by liver after extended cold ischemia to enhance ATP restoration. Provision of these ATP precursors, as components of an enteral formulation may facilitate the repletion of liver ATP and foster early resumption of liver function after an ischemic insult.

Carnitine is a substance that body cells need in order to produce energy from certain types of fat. The liver synthesizes carnitine; consequently severe liver disease disrupts carnitine metabolism throughout the body. This study evaluated the carnitine levels of patients with liver disease before and after liver transplantation. Carnitine was measured in two parts of the blood, blood plasma and red blood cells. Recent research has demonstrated that carnitine distributes itself into two pools or partitions, one being plasma and the other red blood cells. The partitioning factor is simply the ratio of red cell carnitine to plasma carnitine; this ratio was assessed as well. Twenty-eight patients with end-stage (advanced) liver disease who received a liver transplant were included. Before transplantation, red cell and plasma carnitine were both significantly higher than in a normal control group and the partitioning factor was four times normal. Six months after transplantation, plasma and red cell carnitine levels had decreased toward normal but the partitioning factor favored red blood cells 2.3 times over plasma compared to 1.2 in the normal group. This suggested that excess carnitine was being stored in the red cells of patients with liver disease. The authors hypothesize that elevated blood carnitine in liver disease may result from inadequate uptake of carnitine by the liver or excessive leakage of carnitine from the liver and other tissues. Muscle contains large amounts of carnitine. These patients may release carnitine from muscle because they have protein malnutrition, which involves muscle breakdown. The authors conclude that patients with severe liver disease do not show evidence of carnitine deficiency.

The efficacy of various total parenteral nutrition regimens administered for 72 h in supporting the rat after portacaval anastomosis was evaluated. All animals that received amino acid-containing formulas had significantly improved nitrogen balance (p < 0.05), albumin synthetic rates (p < 0.05), and serum albumin concentration (p < 0.05) compared with animals receiving dextrose only. Rats that received the mixed-fuel system containing amino acids, dextrose, and lipid had significantly improved leucine flux and whole body protein synthesis (p < 0.05) compared with animals that received dextrose only, or amino acids and dextrose. Diets composed of dextrose only, amino acids and dextrose, or amino acids and dextrose with the addition of currently available long-chain triglyceride lipid emulsion induced abnormal morphologic changes in the liver. No hepatic morphologic changes were evident in rats that received an isocaloric mixedfuel regimen containing medium- and long-chain triglycerides. The results suggest that mixed-fuel systems containing amino acids and dextrose with lipids are superior to formulas containing dextrose only, or dextrose with amino acids. The improved liver morphology observed in animals given the lipid emulsion system containing medium- and long-chain triglycerides suggests that medium-chain triglycerides may provide an additional benefit in supporting the patient with liver dysfunction.

Correlation of hepatocellular adenine nucleotides in donor liver with clinical posttransplant outcome has recently been reported. Our earlier work with rats has shown that pretreatment of donors with glucose effectively retards hepatocellular ATP losses in livers pre served in Collins' II solution through potentiation of their glycolytic capacity. The primary substrate—i.e., endogenous or exogenous glucose—was not identified.

Recent studies of human donor livers indicate an association between ex vivo hepatocellular adenosine triphosphate and posttransplant graft function. To test the hypothesis that prior glucose loading of donor liver would optimize its adenosine triphosphate production and adenylate energy charge during ex vivo organ preservation, adult male rats were randomized to receive either intravenous dextrose or saline for 44 h. After this infusion, a liver lobe was exposed and freeze-clamped (time 0). The remaining liver was quickly flushed, excised, and stored in Collins' II solution at 2 °C for 8 h. Additional lobes were freeze-clamped at 1, 4, and 8 h. Liver adenosine triphosphate, total nucleoside triphosphates, and energy charge losses were significantly reduced in the dextrose-treated rats in comparison with saline-treated rats during the first 4 h of preservation. Although the livers from rats receiving intravenous dextrose were able to generate lactate, their glycogen stores were not utilized appreciably, suggesting that exogenous glucose served as a substrate for anaerobic glycolysis. Unesterified choline levels of the fasted rat livers were significantly higher than those from the rats receiving intravenous dextrose by the first hour, indicative of increased membrane breakdown. These results indicate that prior infusion of glucose enhances the capacity of the ex vivo liver, presumably through the induction and stabilization of key glycolytic enzymes, to anaerobically generate adenosine triphosphate. Administration of glucose to liver donors before organ procurement may improve posttransplant graft function by reducing the loss of hepatocellular energy, retarding membrane damage, and fostering glycogen storage for use in the early postoperative period.

1. To determine whether the alterations in amino acid metabolism after injury were a result of changes in protein synthesis, whole body tyrosine and individual tissue protein kinetics were estimated 24 h after three different forms of stress in rats. 2. in addition, injured rats were either starved or infused with 180 mg of nitrogen/day (as branched chain amino acids or l-alanine) to ascertain whether the mechanism and degree of nitrogen sparing were unique to branched chain amino acid administration or whether they could be attributed to the infusion of α-amino nitrogen. 3. in the more catabolic types of injury, increased nitrogen loss during starvation appeared to be due to both an increased plasma amino acid appearance and a greater percentage being oxidized. Rates of tyrosine incorporation into whole body protein were also enhanced and could be explained in part by increases in the fractional synthesis rate of hepatic non-secretory protein. 4. Both branched chain amino acid and l-alanine administration reduced endogenous tyrosine oxidation and improved nitrogen balance. However, branched chain amino acid administration significantly increased amino acid incorporation into whole body protein and fractional synthetic rates of skeletal muscle, kidney and hepatic non-secretory protein. 5. It is concluded that the catabolic response to severe injury is consistent with increased rates of plasma amino acid appearance and branched chain amino acid administration spares body protein by improving amino acid utilization for whole body protein synthesis.

The effects of end-stage liver disease and orthotopic liver transplantation on components that modulate cholesterol esterification in plasma were assessed. In comparison with healthy controls, patients with end-stage liver disease had significantly decreased concentrations of lecithin-cholesterol acyltransferase mass, apolipoprotein A-1, total phospholipids, and both total and esterified cholesterol. Elevated phosphatidylcholine and reduced lysophosphatidylcholine fractions indicated impairment of cholesterol esterification by lecithin-cholesterol acyltransferase. Constituent fatty acids of the patients' phospholipids and cholesterol esters manifested increased saturation and a concomitant reduction of polyunsaturated fatty acids, indicative of impaired hepatic elongation and desaturation of essential fatty acids. By the third month after hepatic replacement, the plasma concentrations of total cholesterol, phospholipids, lecithin-cholesterol acyltransferase, and apolipoprotein A-1 were comparable to those of the healthy subjects. Despite the improvement in cholesterol esterification and the rapid normalization of the enzyme and cofactor involved in this process, the percentage of phosphatidylcholine remained significantly higher and the percentages of lysophosphatidylcholine and esterified cholesterol remained significantly lower than in the healthy subjects at 6 mo. Phospholipid and cholesterol ester fatty acid patterns attained normalcy by the sixth month after transplant. We conclude that hepatic transplantation effectively restores cholesterol and essential fatty acid metabolism in patients with end-stage liver disease.

• During the first five days following gastric bypass surgery, 15 patients received near isotonic amino acid solutions that varied in their branched-chain amino acid (BCAA) content and amino acid profiles (15.6%, 50%, or 100% BCAA solutions). Plasma valine concentrations were elevated in patients receiving 50% and 100% BCAA solutions. Plasma alanine concentrations were highest in patients receiving 50% BCAA. Plasma free fatty acids and blood lactate concentrations were unchanged by either the operation or BCAA administration. Serum glucose concentration was unaffected by the different amino acid administrations and followed the pattern induced by stress initially and later by starvation. β-Hydroxybutyrate concentrations increased as starvation proceeded and were highest in patients receiving the 15.6% BCAA solution. Branched-chain amino acid—enriched solutions without additional energy may be administered safely to patients recovering from operative trauma. Plasma amino acid concentrations and fuel substrate profiles appear to follow metabolic patterns determined by the physiologic response to stress and starvation and can be affected by large quantities of BCAAs.(Arch Surg 1987;122:760-764)