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Increase in lipid peroxidation measured by breath pentane output in alcoholic cirrhotic patients
LIVER
Conclusion: Although no changes in the total levels of cytochrome P450 were found future studies have to be performed to estimate possible effects due to changes in specific cytochrome P450 isoenzymes.
0.78 Defective gIucose storage as a cause of insulin resistance in lii ciwhosis M.J.Mlilisr,H.U.Laufz,0. Se&q, 0. Wi//~?~fl, A. Riege~ A. Fenk, H. Can&fat@ F. W. Schmkn Medizinische Hochschu~ Hannover, Abt. Gastroenferologe fologie. Hannover, FRG
und Hepa-
0.80 Increase in lipid peroxidation measured by breath pentane output in alcoholic cirrhotic patients
Insulin resistance is a characteristic feature of liver cirrhosis but its site and cause is still a matter of debate. To get further insight we performed a sequential clamp protocol (0-2h: 1 mu/kg x min t euglycemia, 2-4h: 4mUlkg x min insulin t hyperglycemia of about 165 mg/dl) in 26 patients with liver cirrhosis (10 EtDH-Ci, 8 PBCi and 8 postnecrotic Ci) differing with respect to their clinical (12 CHILD A, 14 CHILD B) and nutritional state (16 BCM higher than 28.5% bw, 10 lower than 28%). Patients were compared with ten age and sex matched controls. Energy expenditure and substrate oxidation rates were determined by indirect calorimetry (DATEX Metabolic monitor). Liver cirrhosis decreased insulin-induced glucose disposal by 44.9% (O-2 h) and 60.1% (2-4h), respectively. This defect was independent of the aetiolcgy of cirrhosis, the duration of the disease, the clinical chemical parameters of liver function, the clinical as well the nutritional state, i.e. muscle mass. Liver cirrhosis did not affect insulin-induced accumulation of plasma lactate, glucose oxidation, carbohydrate-induced lipogenesis and inhibition of lipolysis. By contrast, liver cirrhosis markedly decreased glucose storage (0-2h: -82%; 2-4h: -47%). This defect could not be normalized by matching the glucose disposal to control values (i.e. by increasing plasma insulin), where patients with liver cirrhosis disproportionally increased lactate production as well as lipogenesis. Despite reduced glucosestorage liver cirrhosis increased glucose-induced thermogenesis by +52%, which was most pronounced in patients with a poor nutritional state. We conclude that insulin resistance in liver cirrhosis differs from type 2 diabetic patients and is exclusively due to a defect in muscle glucose storage. This defect is independent of liver function and the clinical as well as the nutritional state and could not be normalized by insulin. Increased glucose-induced thermogenesis contributes to the unfavourable energy balance in patients with liver cirrhosis.
A.VanGoswm,J. Decuyper, M. Cremer and H.A. Ooms Departments of Gasfroenterology and Medical Chemistry, Hbpital Erasme, Brussels, Belgium
0.79 The influenceof diierent fat emulsionson cytochrome P450 in rat liver
The determination of n-pentane in exhaled air is considered to be a good index of lipid peroxidation magnitude. However, because n-pantane is mostly metabolised by the liver, this last assertion has been cautioned in case of hepatic insufficiency and especially in case of decreased microsomial function. Thus, we decided to measure n-pentane excretion in cirrhotic patients and to correlate it to “‘Caminopyrine breath test which is a reliable reflect of the hepatic microsomial function. Patients: 10 heaithy volunteers (3 females, 7 males; mean age: 34~) and 9 patients (1 female, 8 males; mean age: 51 y) wlh alcoholic cirrhosis proven by hepatic biopsy. The cirrhosis were classified as Child B for 7 patients and Child C for 2 patients. Results are expressed in rmddl of exhated air. Methods: Breath pentane measurement. After a washout period of 4 minutes, expired air was collected into a Tedlar bag. An aliquot was analyzed by gas chromatography (Hewlett-Packard 5890 equipped with a Poraplot Q column from Chrompack) with a thermo-desorption cryo-focusing technique for the injection (TCT from Chrompack). “‘C-aminopyrine Breath Test: the samples were obtained 2 hours after oral administration of “C-aminopyrine. The results are expressed as percentage of administered “C-aminopyrine. The results are expressed as percentage of administered 14C excreted in 14C02 over 2 hours. Results: The excretion of pentane in control subjects (5.56 + 2.3) was significantly lower than in cirrhotic subjects (10.06 ? 3.6); p < 0.004). The values of “C-aminopyrine breath test (1.44 i 0.98) were well below the normal range of our laboratory (from 5.0 to 7.0). There was no correlation between n-pentane excretion and “C-aminopyrine breath test. Thus in cirrhotic patients with severely impaired liver function, the increased excretion of pentane is not correlated with liver microsomial function. These data suggest that lipid peroxidation is really increased in alcoholic cirrhotic patients who are known to be deficient in antioxydant system.
R. Wnonssonand 1. Johansson Vifrum lnstitufe for Human Nutrition, Stockholm, Sweden
0.81 Portal ammonia loadinghas no effect on hepatic amino acid fluxes
The aim of this study was to investigate the possible effect of intravenous infusion of a long-chain triglyceride (LCT) emulsion or MCFAILCFA-containing structured triglyceride (STG) emulsion on the liver cytochrome P450 levels in the rat. Methods: Rats were given a intravenous infusion during 20 hours/day for a period of 13 days. The dose was 90 ml/kg body weight/day of a 20% emulsion (leg fat/kg BW/day), corresponding to an energy intake of 0.78 and 0.71 MJ/ko BW/dav from the LCT and the STG fat emulsions, respectively. Control rats received no infusion. All rats were given standard diet and water ad libitum. The animals were sacrificed by heart puncture under anaesthesia, the liver was removed and microsomes were prepared using standard methods. Cytochrome P450 was measured by CO-diierence spectra. Protein content was determined by nitrogen analysis. Resutt~ The animals showed no adverse effects in any group. No significant influence of either LCT or STG fat emulsions on the total levels of cytochrome P450 were found.
P.L.M.Reijven, N.E.P. Deutz and P.B. Soeters Dept. Surg., Univ. Limburg, Maastricht, The Netherlands Although the liver is the main ammonia (Amm) detoxificating organ, regulatory mechanisms in vivo are not completely understood. We studi the in vivo effects of a portal Amm-acetate (AmmAc) load on hepatic Amm, Ureaand Amino acid fluxes in female pigs (20-24kg, n = 7). In 1620 h fasted Pigs AmmAc (156mM) was infused in the portal vein for 3h with an initial rate of 80 mi/h, increased 60 ml/h every 30 min. Results: At t = 3 h arterial Amm was increased from 23 + 7 to 184 ? 47 p.M (p
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a-AminoN FE.Amn
Conclusion: Although no changes in the total levels of cytochrome P450 were found future studies have to be performed to estimate possible effects due to changes in specific cytochrome P450 isoenzymes.
0.78 Defective gIucose storage as a cause of insulin resistance in lii ciwhosis M.J.Mlilisr,H.U.Laufz,0. Se&q, 0. Wi//~?~fl, A. Riege~ A. Fenk, H. Can&fat@ F. W. Schmkn Medizinische Hochschu~ Hannover, Abt. Gastroenferologe fologie. Hannover, FRG
und Hepa-
0.80 Increase in lipid peroxidation measured by breath pentane output in alcoholic cirrhotic patients
Insulin resistance is a characteristic feature of liver cirrhosis but its site and cause is still a matter of debate. To get further insight we performed a sequential clamp protocol (0-2h: 1 mu/kg x min t euglycemia, 2-4h: 4mUlkg x min insulin t hyperglycemia of about 165 mg/dl) in 26 patients with liver cirrhosis (10 EtDH-Ci, 8 PBCi and 8 postnecrotic Ci) differing with respect to their clinical (12 CHILD A, 14 CHILD B) and nutritional state (16 BCM higher than 28.5% bw, 10 lower than 28%). Patients were compared with ten age and sex matched controls. Energy expenditure and substrate oxidation rates were determined by indirect calorimetry (DATEX Metabolic monitor). Liver cirrhosis decreased insulin-induced glucose disposal by 44.9% (O-2 h) and 60.1% (2-4h), respectively. This defect was independent of the aetiolcgy of cirrhosis, the duration of the disease, the clinical chemical parameters of liver function, the clinical as well the nutritional state, i.e. muscle mass. Liver cirrhosis did not affect insulin-induced accumulation of plasma lactate, glucose oxidation, carbohydrate-induced lipogenesis and inhibition of lipolysis. By contrast, liver cirrhosis markedly decreased glucose storage (0-2h: -82%; 2-4h: -47%). This defect could not be normalized by matching the glucose disposal to control values (i.e. by increasing plasma insulin), where patients with liver cirrhosis disproportionally increased lactate production as well as lipogenesis. Despite reduced glucosestorage liver cirrhosis increased glucose-induced thermogenesis by +52%, which was most pronounced in patients with a poor nutritional state. We conclude that insulin resistance in liver cirrhosis differs from type 2 diabetic patients and is exclusively due to a defect in muscle glucose storage. This defect is independent of liver function and the clinical as well as the nutritional state and could not be normalized by insulin. Increased glucose-induced thermogenesis contributes to the unfavourable energy balance in patients with liver cirrhosis.
A.VanGoswm,J. Decuyper, M. Cremer and H.A. Ooms Departments of Gasfroenterology and Medical Chemistry, Hbpital Erasme, Brussels, Belgium
0.79 The influenceof diierent fat emulsionson cytochrome P450 in rat liver
The determination of n-pentane in exhaled air is considered to be a good index of lipid peroxidation magnitude. However, because n-pantane is mostly metabolised by the liver, this last assertion has been cautioned in case of hepatic insufficiency and especially in case of decreased microsomial function. Thus, we decided to measure n-pentane excretion in cirrhotic patients and to correlate it to “‘Caminopyrine breath test which is a reliable reflect of the hepatic microsomial function. Patients: 10 heaithy volunteers (3 females, 7 males; mean age: 34~) and 9 patients (1 female, 8 males; mean age: 51 y) wlh alcoholic cirrhosis proven by hepatic biopsy. The cirrhosis were classified as Child B for 7 patients and Child C for 2 patients. Results are expressed in rmddl of exhated air. Methods: Breath pentane measurement. After a washout period of 4 minutes, expired air was collected into a Tedlar bag. An aliquot was analyzed by gas chromatography (Hewlett-Packard 5890 equipped with a Poraplot Q column from Chrompack) with a thermo-desorption cryo-focusing technique for the injection (TCT from Chrompack). “‘C-aminopyrine Breath Test: the samples were obtained 2 hours after oral administration of “C-aminopyrine. The results are expressed as percentage of administered “C-aminopyrine. The results are expressed as percentage of administered 14C excreted in 14C02 over 2 hours. Results: The excretion of pentane in control subjects (5.56 + 2.3) was significantly lower than in cirrhotic subjects (10.06 ? 3.6); p < 0.004). The values of “C-aminopyrine breath test (1.44 i 0.98) were well below the normal range of our laboratory (from 5.0 to 7.0). There was no correlation between n-pentane excretion and “C-aminopyrine breath test. Thus in cirrhotic patients with severely impaired liver function, the increased excretion of pentane is not correlated with liver microsomial function. These data suggest that lipid peroxidation is really increased in alcoholic cirrhotic patients who are known to be deficient in antioxydant system.
R. Wnonssonand 1. Johansson Vifrum lnstitufe for Human Nutrition, Stockholm, Sweden
0.81 Portal ammonia loadinghas no effect on hepatic amino acid fluxes
The aim of this study was to investigate the possible effect of intravenous infusion of a long-chain triglyceride (LCT) emulsion or MCFAILCFA-containing structured triglyceride (STG) emulsion on the liver cytochrome P450 levels in the rat. Methods: Rats were given a intravenous infusion during 20 hours/day for a period of 13 days. The dose was 90 ml/kg body weight/day of a 20% emulsion (leg fat/kg BW/day), corresponding to an energy intake of 0.78 and 0.71 MJ/ko BW/dav from the LCT and the STG fat emulsions, respectively. Control rats received no infusion. All rats were given standard diet and water ad libitum. The animals were sacrificed by heart puncture under anaesthesia, the liver was removed and microsomes were prepared using standard methods. Cytochrome P450 was measured by CO-diierence spectra. Protein content was determined by nitrogen analysis. Resutt~ The animals showed no adverse effects in any group. No significant influence of either LCT or STG fat emulsions on the total levels of cytochrome P450 were found.
P.L.M.Reijven, N.E.P. Deutz and P.B. Soeters Dept. Surg., Univ. Limburg, Maastricht, The Netherlands Although the liver is the main ammonia (Amm) detoxificating organ, regulatory mechanisms in vivo are not completely understood. We studi the in vivo effects of a portal Amm-acetate (AmmAc) load on hepatic Amm, Ureaand Amino acid fluxes in female pigs (20-24kg, n = 7). In 1620 h fasted Pigs AmmAc (156mM) was infused in the portal vein for 3h with an initial rate of 80 mi/h, increased 60 ml/h every 30 min. Results: At t = 3 h arterial Amm was increased from 23 + 7 to 184 ? 47 p.M (p
AlTWt”
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CN
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-6.2t4.2
62+6
1w
-16Ot58
-0.9m3
4.6tl 2
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-23.5~21.1
73m3
130
-3DOi40
-1,il.l
78214
33.1+11 6
-3.4t2.7
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2 00
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3 00
-48.Ok94
-4.a+2.4
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442i102
-6 1t2.2
69t17
ANOVAf=Or3h.'p<005."p
25
a-AminoN FE.Amn