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P.44 Glycogen degradation during acute liver disease and following orthotopic liver transplantation
Results: The mean content of muscle glycogen in the 29 patients was 4.2 +_ 2.0mg/g muscle. A significant correlation was found between the body mass index and muscle glycogen content. The patients were divided into two groups according to their muscle glycogen contents. Group A was comprised of the 6 patients whose glycogen contents were less than mean _+ 1SD. The remaining 23 patients formed Group B. One patient in Group A died with multiorgan failure resulting from initial poor graft function. Two patients in Group A who survived had a reversible initial poor graft function. The mean content of their old-liver glycogen was 14.5 _+ 12.0mg/g.liver. There was no significant difference in the liver glycogen content between the two groups. No significant correlation was found between the glycogen content of muscle and old liver. In the patients with depleted muscle glycogen content, the plasma concentration of interleukin-6 increased markedly soon after operation, and was associated with an increased endotoxin concentration. This cytokine response was preceded by an increased lactate/pyruvate ratio and followed by increased concentrations of hepatocyte growth factor and hyaluronic acid, and other factors that reflected graft viability. Conclusions: The nutritional status of the recipient may be relevant to the increased concentrations of cytokines and endotoxin during liver transplantation. The metabolic derangement indicated by the persistence of high lactate levels may also be relevant to the exaggerated responses of cytokine and endotoxin. The striking cytokine response observed together with endotoxemia in the glycogendepleted recipients may affect the graft viability or liver regeneration. The preoperative nutritional status of patients awaiting liver transplantation may be one of the factors affecting graft viability following liver transplantation.
started TPN at 13.4 + 4.9 vs 11.5 + 3.0 days, respectively. We did not observe differences in A, PA, T, and RBP during the study. For groups G and WP, at day 14 A was 3.6 _+0.5 vs 3.6 + 0.4g/dl, T 159 _+9 vs 154 _+ 30 mg/dl, PA 15.5 _+2.2 vs 16.0 + 5.2 mg/dl and RBP 2.6 + 1.0 vs 3.6 + 0.6 mg/dl. Conclusions: In this first interim report, oral gluatmine does not improve the effects of whole protein supplements on GI toxicity of Qx, use of TPN or serum protein concentrations in autologous hemopoietic transplant patients. The definition of an eventually more effective dose of G or WP merits further research.
P,42 Muscle glycogen content of liver transplant recipients and its relation to post-operative cytokine response and subsequent graft liver function C. Miki, K. Iriyama and P. McMaster Department of Surgery II, Mie University Medical School, Japan. Liver Unit, Queen Elizabeth Hospital, Birmingham, UK. Background: Malnutrition is a risk factor for mortality and morbidity after liver transplantation. The purpose of this study was to clarify the pathophysiologic mechanism underlying impaired outcome in malnourished recipients. Patients: Twenty-nine consecutive liver transplant recipients. Methods: Glycogen contents of patient's abdominal muscle and old liver were measured for the assessment of nutritional status. Arterial blood samples were obtained during and after surgery, and the plasma concentrations of tumour necrosis factor-cq interleukin-l~, interleukin-6, endotoxin, lactate, pyruvate, hepatocyte growth factor and hyaluronic acid were determined.
Session 1 -TOPIC
7: LIVER, K I D N E Y
P.44 Glycogen degradation during acute liver disease and following orthotopic liver transplantation M. D. Patel 1, S. M. Gabe2'3, R. Taylor2, A. Baker 2, V. R. Preedy2, D. Pryot2, D. B. A. Silk3, R. Williams 2 and G. K. Grimble t 1Roehampton Institute, London SW15, 2Kings College Hospital, London SE5, 3Central Middlesex Hospital, London NW10.
P,43 The effects of short term parenteral nutrition on human liver protein metabolism H. Barle*, B. Nyberg**, P. Essen*, K. Andersson*, M. McNurlan***, J. Wemerman* and R Garlick*** * Dept of Anesthesiology and Intensive Care and ** Dept of Surgery, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden and ***Dept of Surgery Stony Brook Medical Center, State University of New York at Stony Brook, USA. Background and aim: The knowledge of the effects of nutrition on liver
We have developed a novel HPLC assay for urinary glucosyltetrasaccharide (GIc4), a characteristic fragment of glycogen which is an index of breakdown. We wished to determine the history of perioperative glycogen metabolism in patients with fulminant liver failure undergoing liver transplantation. Desalted urine samples were analysed by anion-exchange HPLC with pulsed amperometric detection using a linear gradient of CHsCOONa (0-500 mmol/I) in 60 mmol/I NaOH at 0.8 ml/min on a PAl00 column. The assay is linear from 100 ~g/I to 5 mg/I whilst inter-assay variance was 7.31%. 24 hour urine samples were taken from 5 adults (5M, age 17-35yrs) and 5 children (4M, 1F, age 2-11 yrs). Data are expressed as mg GIc4/mmol creatinine (mean _+SEM).
protein metabolism emanates merely from animal studies. The aims of this study were to characterize the effects of short time parenteral nutrition on two main parameters of human liver protein metabolism, namely the hepatic free amino acid concentrations and the fractional synthesis rate of total liver protein. Method: 30 patients undergoing elective laparoscopic cholecystectomy were randomized into two groups; controls (no treatment, n = 16) and TPN group (n = 14). The patients in the TPN group received parenteral nutrition for 8.6 __.1.0 hours, with the following composition: 17.5 kcal/kg body weight, 50% fat, 50% carbohydrates, 0.1 N/kg). In the beginning of the operation a liver biopsy specimen was taken, for the analysis of liver amino acid concentrations, employing ion exchange chromatography. In 16 of the patients, a flooding dose of L[2H5]phenylalanine was administered over 10 minutes and a second liver biopsy specimen was taken at 31 _+4 minutes later. Stable isotope enrichments of plasma free phenylalanine and total liver protein were analysed employing gas chromatography mass spectrometry (GC-MS), for the calculation of fractional synthesis rate (FSR) of total liver protein.
Pre-transpL (days1-3) Days1-4 Days5-7
1.13-+0.23" 1.21-+0.31 2.32-+0.19" 2.72-+1.14 2.44-+0.28* 0.83-+0.28 * P< 0.05, Student'st-test. Comparative data for children on days 1-4 and days 5-7 post-transplant were, 20.81 _+4.61 and 17.32 + 10.75 mg/mmol, respectively, indicating higher GIc4 excretion per unit of lean body mass. This reflects relative organ sizes during growth and development. Acute liver failure reduced hepatic glycogen and unsurprisingly these data show that transplantation restores this as judged from the increase in its breakdown product. It is significant, however, that liver failure did not completely suppress GIc4 excretion, and that residual excretion indicates the significance of muscle glycogen breakdown.
Results: FSR, total liver protein (%/d) Alanine (mmol/kg ww liver) Essential aa (mmol/kg ww liver) Total aa (mmol/kg ww liver)
Controls
TPN group
P
17.7 -+3.8 1.09 -+0.53 1.08 -+0.23 23.4 _+4.5
15.2 -+4.7 1.61 -+0.61 1.59 -+0.40 26.1 _+2.4
NS <0.05 <0.001 NS
Posttransplantation Days8-12 Days13-23 Days24-37
P.45 Small intestinal ammonia production is a major determinant of post-feeding hyperammonemia in liver cirrhosis M. Plauth, A.-E. Roske, E. Roth*, D. Stockheim**, R. Ziebig***, P. Romaniuk**, U. Wruck & H. Lochs Medizinische Klinik, Institute f. **Rdntgendiag. and ***Kiln. Biochem. & Pathobiochem., CharitY, Berlin, Germany, and *Chirurgische Forschungslaboratorien, AKH, Wien, Austria.
Conclusion: In conclusion, short term total parenteral nutrition induced specific changes of the free hepatic amino acid concentrations, whereas total liver protein synthesis remained unaffected by TPN.
In cirrhotic patients, kinetics of intestinal ammonia (AMM) production and 34
started TPN at 13.4 + 4.9 vs 11.5 + 3.0 days, respectively. We did not observe differences in A, PA, T, and RBP during the study. For groups G and WP, at day 14 A was 3.6 _+0.5 vs 3.6 + 0.4g/dl, T 159 _+9 vs 154 _+ 30 mg/dl, PA 15.5 _+2.2 vs 16.0 + 5.2 mg/dl and RBP 2.6 + 1.0 vs 3.6 + 0.6 mg/dl. Conclusions: In this first interim report, oral gluatmine does not improve the effects of whole protein supplements on GI toxicity of Qx, use of TPN or serum protein concentrations in autologous hemopoietic transplant patients. The definition of an eventually more effective dose of G or WP merits further research.
P,42 Muscle glycogen content of liver transplant recipients and its relation to post-operative cytokine response and subsequent graft liver function C. Miki, K. Iriyama and P. McMaster Department of Surgery II, Mie University Medical School, Japan. Liver Unit, Queen Elizabeth Hospital, Birmingham, UK. Background: Malnutrition is a risk factor for mortality and morbidity after liver transplantation. The purpose of this study was to clarify the pathophysiologic mechanism underlying impaired outcome in malnourished recipients. Patients: Twenty-nine consecutive liver transplant recipients. Methods: Glycogen contents of patient's abdominal muscle and old liver were measured for the assessment of nutritional status. Arterial blood samples were obtained during and after surgery, and the plasma concentrations of tumour necrosis factor-cq interleukin-l~, interleukin-6, endotoxin, lactate, pyruvate, hepatocyte growth factor and hyaluronic acid were determined.
Session 1 -TOPIC
7: LIVER, K I D N E Y
P.44 Glycogen degradation during acute liver disease and following orthotopic liver transplantation M. D. Patel 1, S. M. Gabe2'3, R. Taylor2, A. Baker 2, V. R. Preedy2, D. Pryot2, D. B. A. Silk3, R. Williams 2 and G. K. Grimble t 1Roehampton Institute, London SW15, 2Kings College Hospital, London SE5, 3Central Middlesex Hospital, London NW10.
P,43 The effects of short term parenteral nutrition on human liver protein metabolism H. Barle*, B. Nyberg**, P. Essen*, K. Andersson*, M. McNurlan***, J. Wemerman* and R Garlick*** * Dept of Anesthesiology and Intensive Care and ** Dept of Surgery, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden and ***Dept of Surgery Stony Brook Medical Center, State University of New York at Stony Brook, USA. Background and aim: The knowledge of the effects of nutrition on liver
We have developed a novel HPLC assay for urinary glucosyltetrasaccharide (GIc4), a characteristic fragment of glycogen which is an index of breakdown. We wished to determine the history of perioperative glycogen metabolism in patients with fulminant liver failure undergoing liver transplantation. Desalted urine samples were analysed by anion-exchange HPLC with pulsed amperometric detection using a linear gradient of CHsCOONa (0-500 mmol/I) in 60 mmol/I NaOH at 0.8 ml/min on a PAl00 column. The assay is linear from 100 ~g/I to 5 mg/I whilst inter-assay variance was 7.31%. 24 hour urine samples were taken from 5 adults (5M, age 17-35yrs) and 5 children (4M, 1F, age 2-11 yrs). Data are expressed as mg GIc4/mmol creatinine (mean _+SEM).
protein metabolism emanates merely from animal studies. The aims of this study were to characterize the effects of short time parenteral nutrition on two main parameters of human liver protein metabolism, namely the hepatic free amino acid concentrations and the fractional synthesis rate of total liver protein. Method: 30 patients undergoing elective laparoscopic cholecystectomy were randomized into two groups; controls (no treatment, n = 16) and TPN group (n = 14). The patients in the TPN group received parenteral nutrition for 8.6 __.1.0 hours, with the following composition: 17.5 kcal/kg body weight, 50% fat, 50% carbohydrates, 0.1 N/kg). In the beginning of the operation a liver biopsy specimen was taken, for the analysis of liver amino acid concentrations, employing ion exchange chromatography. In 16 of the patients, a flooding dose of L[2H5]phenylalanine was administered over 10 minutes and a second liver biopsy specimen was taken at 31 _+4 minutes later. Stable isotope enrichments of plasma free phenylalanine and total liver protein were analysed employing gas chromatography mass spectrometry (GC-MS), for the calculation of fractional synthesis rate (FSR) of total liver protein.
Pre-transpL (days1-3) Days1-4 Days5-7
1.13-+0.23" 1.21-+0.31 2.32-+0.19" 2.72-+1.14 2.44-+0.28* 0.83-+0.28 * P< 0.05, Student'st-test. Comparative data for children on days 1-4 and days 5-7 post-transplant were, 20.81 _+4.61 and 17.32 + 10.75 mg/mmol, respectively, indicating higher GIc4 excretion per unit of lean body mass. This reflects relative organ sizes during growth and development. Acute liver failure reduced hepatic glycogen and unsurprisingly these data show that transplantation restores this as judged from the increase in its breakdown product. It is significant, however, that liver failure did not completely suppress GIc4 excretion, and that residual excretion indicates the significance of muscle glycogen breakdown.
Results: FSR, total liver protein (%/d) Alanine (mmol/kg ww liver) Essential aa (mmol/kg ww liver) Total aa (mmol/kg ww liver)
Controls
TPN group
P
17.7 -+3.8 1.09 -+0.53 1.08 -+0.23 23.4 _+4.5
15.2 -+4.7 1.61 -+0.61 1.59 -+0.40 26.1 _+2.4
NS <0.05 <0.001 NS
Posttransplantation Days8-12 Days13-23 Days24-37
P.45 Small intestinal ammonia production is a major determinant of post-feeding hyperammonemia in liver cirrhosis M. Plauth, A.-E. Roske, E. Roth*, D. Stockheim**, R. Ziebig***, P. Romaniuk**, U. Wruck & H. Lochs Medizinische Klinik, Institute f. **Rdntgendiag. and ***Kiln. Biochem. & Pathobiochem., CharitY, Berlin, Germany, and *Chirurgische Forschungslaboratorien, AKH, Wien, Austria.
Conclusion: In conclusion, short term total parenteral nutrition induced specific changes of the free hepatic amino acid concentrations, whereas total liver protein synthesis remained unaffected by TPN.
In cirrhotic patients, kinetics of intestinal ammonia (AMM) production and 34