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K Träger

Publications and source records attributed to K Träger.

29 records · Page 2Linked to original sources
PubMed1997

Metabolic and calorigenic effects of dopexamine in healthy volunteers.

OBJECTIVE: To evaluate metabolic and calorigenic effects of dopexamine in healthy volunteers. DESIGN: Prospective, randomized trial. SETTING: Laboratory of the University Department of Anesthesiology. SUBJECTS: Eight volunteers. INTERVENTIONS: After a control period, dopexamine was administered using four infusion rates (0.75, 1.5, 3.0, and 6.0 microg/kg/min). MEASUREMENTS AND MAIN RESULTS: Blood pressure, heart rate, oxygen consumption (VO2), and the plasma concentration of potassium, glucose, lactate, and norepinephrine were measured. Typical hemodynamic responses were seen. VO2 increased from 122 +/- 11 (SD) to 150 +/- 9 mL/min/m2 during the highest dopexamine infusion rate. Plasma potassium concentration decreased only during the highest infusion rate. Plasma glucose concentration increased during infusion rates of 3 and 6 microg/kg/min of dopexamine, from 90 +/- 5 to 99 +/- 5 mg/dL (5.0 +/- 0.3 to 5.5 +/- 0.3 mmol/L), and from 87 +/- 7 to 103 +/- 11 mg/dL (4.8 +/- 0.4 to 5.7 +/- 0.6 mmol/L), respectively. Lactate did not increase during dopexamine infusion. Plasma norepinephrine concentration increased during all four infusion rates. CONCLUSION: It was not possible to differentiate the adrenergic receptor subtype responsible for the calorigenic and metabolic effects, since the putative beta2 adrenergic-receptor agonist, dopexamine, caused an increase in the plasma concentration of the beta1 adrenergic-receptor agonist, norepinephrine. Since beta2 adrenergic receptor-mediated effects such as hypokalemia were found only at infusion rates > or = 3 microg/kg/min, the effects of dopexamine at infusion rates < 3 microg/kg/min may be mainly mediated by stimulation of dopaminergic receptors and the indirect sympathomimetic action.

Adrenergic beta-Agonists↗
PubMed1996

The effect of human growth hormone therapy on L-(methyl-2H3)-leucine turnover and urinary pseudouridine concentration in patients with Ullrich-Turner syndrome.

UNLABELLED: The effect of daily human growth hormone (hGH) injections (3 I.U./m2/day) on tissue anabolism was determined in six patients with Ullrich-Turner syndrome (XO) (8.7-19 years of age) using novel techniques such as whole body leucine kinetics during continuous infusion of L-(Methyl-2H3)-leucine and urinary pseudouridine (5-ribosyluracil) excretion on the one hand and traditional methods like serum urea and amino acid concentrations on the other. Pseudouridine is only found in ribonucleic acid (RNA) and is neither reincorporated nor catabolically broken down and is therefore considered an ideal index of whole body RNA turnover. The mean L-(Methyl-2H3)-leucine turnover of the six XO patients before hGH was 1.90 +/- 0.15 mumoles/kg per minute. After 3 months of hGH-treatment it had increased in three patients, whereas it had decreased in the other three. The results obtained with the stable isotope technique were correlated with the urinary pseudouridine concentrations (r = 0.68; P < 0.01). The growth rates were positively correlated with leucine turnover (r = 0.63; P < 0.02) and urinary pseudouridine concentration (r = 0.73; P < 0.006) as well as negatively correlated with the serum urea concentrations r = -0.62; P < 0.03). The decrease in the individual serum urea concentrations were tightly correlated with the hGH induced change in growth rate (r = -0.90; P < 0.01). The individual bone ages were negatively correlated with the hGH induced changes in leucine turnover (r = -0.77; P < 0.003) as well as with the urinary pseudouridine concentrations (r = -0.87; P < 0.0002). The hGH effect on leucine and RNA turnover, showing effectiveness only until a developmental age between 11 and 12 years, leads the discussion of the ideal moment of oestrogen supplementation when girls with Ullrich-Turner syndrome are treated with hGH in early adolescence. CONCLUSION: The protein metabolism of patients with Ullrich-Turner syndrome is influenced by hGH in an age dependent manner. In a clinical setting, pseudouridine, an easily determined derivative of ribonucleic acids, may be able to replace the tedious work with expensive stable isotopes when questions related to tissue anabolism are to be answered.

Adolescent↗
PubMed1996

[Changes in various metabolic parameters following bloodletting].

OBJECTIVE: We investigated hypovolaemia induced by bloodletting, accompanied by statistically significant, but clinically irrelevant increase of heart rate together with unchanged blood pressure, with regard to hepatic glucose production as well as alanine and glycerol turnover rates. METHODS: Healthy male volunteers (n = 18) were bled 15 ml/kg body weight over 20 min and remained hypovolaemic for 60 minutes. Heart rate was recorded by ECG and blood pressure by an oscillometric device. Before and after bloodletting hepatic glucose production as well as alanine and glycerol turnover rates were determined using the stable isotopes 6.6-D2-glucose, 15N-alanine and D5-glycerol as tracers. Simultaneously, the blood concentrations of adrenaline, noradrenaline, free fatty acids and glycerol were measured. RESULTS: Bleeding did not change the mean arterial blood pressure, but increased the heart rate significantly from 61 +/- 9 to 70 +/- 13 1/ min. Noradrenaline levels increased significantly from 1.16 +/- 0.41 to 2.15 +/- 0.69 nmol/l. Hepatic glucose production (HGP) as well as alanine (AlaTO) and glycerol turnover (GlyTO) decreased significantly during hypovolaemia. HGP fell from 2.72 +/- 0.29 to 2.56 +/- 0.28 mg/kg/min, AlaTO from 0.71 +/- 0.27 to 0.53 +/- 0.25 mg/kg/min and GlyTO from 4.9 +/- 2.1 to 3.8 +/- 1.4 mumol/kg/min, respectively. The blood levels of adrenaline, free fatty acids and glycerol did not change during the study. DISCUSSION: In respect of clinical signs, the cardiovascular status of the volunteers was stable after bleeding. In contrast, the decrease of HGP as well as the drop in alanine and glycerol turnover rates might be interpreted as a sign of an altered functional status of single organs, induced by changes of regional perfusion.

Adult↗
PubMed1995

Effects of PEEP ventilation on liver metabolism.

OBJECTIVE: To study the influence of positive endexpiratory pressure (PEEP) ventilation on metabolic parameters with specific regard to liver metabolism. DESIGN: Prospective experimental study on the effects of PEEP ventilation on hemodynamic and gas exchange as well as metabolic parameters, i.e. hepatic glucose production, arterial, hepatic and portal venous insulin, glucagon, free fatty acid (FFA), glycerol, beta-hydroxybutyrate and lactate concentrations. SETTING: Experimental Laboratory Unit of the University Hospital. ANIMALS: 10 Labrador Beagle dogs (18-22 kg) were studied. INTERVENTIONS: Animals were ventilated with PEEP of 0, 7.5, 15, and 0 mm Hg, each level lasting 2 h. RESULTS: PEEP 15 significantly increased heart rate from 110(70) to 220(55) beats/min and decreased cardiac output from 2.5 (2.0) to 1.5 (0.8) l/min. This was associated with significant increases in mean pulmonary artery pressure, pulmonary artery occlusion pressure, portal and hepatic venous pressure, whereas mean systemic pressure did not change. While whole-body oxygen consumption and respiratory quotient remained constant, whole-body oxygen delivery significantly decreased from 456(266) to 294(168) ml/min during PEEP 15 concomitant to augmented whole-body oxygen extraction (from 27(34) to 51(33)%). Oxygen extraction from the splanchnic organs increased from 41(31) to 81(30)%. Hepatic venous oxygen tension (PhvO2) and hemoglobin oxygen saturation (ShvO2) during PEEP 15 decreased from 41(18) to 28(47) mm Hg and from 60(31) to 18(66)%, respectively. Hepatic glucose production was significantly stimulated from 3.44(1.44) to 3.92(1.83) mg/kg/min at PEEP 15. Arterial and portalvenous glucagon/insulin ratios did not change. FFA and glycerol concentrations depending on PEEP levels were significantly higher in the hepatic artery and portal vein than in the hepatic vein. Compared to portal venous and arterial hepatic concentrations, hepatic venous beta-hydroxybutyrate significantly increased with rising PEEP levels. CONCLUSIONS: Low values of PhvO2 and ShvO2 during PEEP 15 gave evidence for hypoxia of the liver. This was associated with a stimulated hepatic glucose production rate accompanied by enhanced hepatic uptake and utilization of FFA serving as fuel substrates. As the rate of gluconeogenesis is a major determinant of hepatic oxygen consumption these metabolic effects of PEEP ventilation have to be considered during states of critical illness.

Animals↗
PubMed1994

Glucose and urea production and leucine, ketoisocaproate and alanine fluxes at supraphysiological plasma adrenaline concentrations in volunteers.

OBJECTIVE: To determine the magnitude and time course of adrenergic effects on metabolism in volunteers and possible implications for the use of sympathomimetics in the critically ill. DESIGN: Descriptive laboratory investigation. SUBJECTS: 7 volunteers. INTERVENTION: Primed continuous infusions of stable isotope tracers ([15N2]-urea, [6,6-D2]-glucose, [methyl-D3]-L-leucine, [15N]-L-alanine) were used. After isotopic steady state had been reached an infusion of adrenaline (0.1 microgram/kg/min) was administered (4 h). Isotopic enrichment was measured using gas chromatography-mass spectrometry and the corresponding rates of appearance were calculated. MEASUREMENTS AND MAIN RESULTS: Glucose production increased from 14.1 +/- 1.2 to 21.5 +/- 2.0 mumol/kg/min (p < 0.05) after 80 min of adrenergic stimulation and then decreased again to 17.9 +/- 1.2 mumol/kg/min after 240 min. Leucine and ketoisocaproate (KIC) fluxes were 2.3 +/- 0.2 and 2.6 +/- 0.2 mumol/kg/min, respectively, at baseline and gradually decreased to 1.8 +/- 0.2 and 2.2 +/- 0.1 mumol/kg/min, respectively, after 240 min of adrenaline infusion (both p < 0.05). Alanine flux increased from 3.7 +/- 0.5 to 6.9 +/- 0.9 mumol/kg/min (p < 0.05) after 80 min of adrenergic stimulation. Urea production slightly decreased from 4.8 +/- 0.9 to 4.3 +/- 0.8 mumol/kg/min during adrenaline (p < 0.05). CONCLUSIONS: Adrenaline induced an increase in glucose production lasting for longer than 240 min. The decrease in leucine and KIC flux suggests a reduction in proteolysis, which was supported by the decrease in urea production. The increase in alanine flux is therefore most likely due to an increase in de-novo synthesis. The ammonia donor for alanine synthesis in peripheral tissues and the target for ammonia after alanine deamination in the liver remain to be investigated. These results indicate that adrenaline infusion most probably will not promote already enhanced proteolysis in critically ill patients. Gluconeogenesis is an energy consuming process and an increase may deteriorate hepatic oxygen balance in patients.

Adult↗
PubMed1993

Evidence for inverse regulation of high and low affinity binding sites for (-)125iodocyanopindolol in human mononuclear leucocytes during epinephrine infusion.

As we have shown earlier (-)125Iodocyanopindolol (125ICYP) binding to beta-adrenoceptors (beta-AR) in human mononuclear leucocytes (MNL) yields evidence for the existence of high affinity (Bhiaff) and low affinity (Bloaff) binding sites. We studied the regulation of these 2 classes of binding sites during 240 min of (-)-epinephrine (EPI) infusion (0.1 microgram/kg/min) (n = 8) in male healthy volunteers. Saturation experiments were performed on MNL membranes with 125ICYP over a large concentration range (1-550 pmol/l). Binding parameters were calculated by computer analysis assuming 2 classes of binding sites. We found a preinfusion value of 830 +/- 50 [sites/cell] (KD = 1.5 +/- 0.2 pmol/l) of Bhiaff binding sites and 5210 +/- 510 [sites/cell] (KD = 420 +/- 80 pmol/l) of Bloaff. During EPI infusion we observed biphasic modulation of the Bhiaff and an inverse modulation of the Bloaff. After 40 min of EPI Bhiaff increased to 1970 +/- 280 [sites/cell] (KD = 4.2 +/- 0.8 pmol/l), whereas Bloaff decreased to 2720 +/- 280 [sites/cell] (KD = 140 +/- 70 pmol/l); despite constant plasma epinephrine concentration (PEC) after 240 min of EPI Bhiaff changed to 1310 +/- 240 [sites/cell] (KD = 2.8 +/- 1.0 pmol/l) vs. 4370 +/- 760 [sites/cell] (KD = 190 +/- 100 pmol/l) Bloaff. These results suggest an interdependent inverse modulation of the 2 classes of binding sites for 125ICYP on MNL during EPI infusion.

Binding, Competitive↗
PubMed1993

Effects of xylitol on carbohydrate and protein metabolism after trauma and during sepsis.

INTRODUCTION: Total parenteral nutrition (TPN) after trauma and during sepsis has two major goals. One is the reduction of increased protein catabolism, the second is to avoid hyperglycemia and enhanced hepatic gluconeogenesis. Glucose and xylitol differ in their utilization rates after trauma and during sepsis. Whole-body glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects on hepatic glucose production and protein sparing, we conducted two animal and two clinical studies. METHODS: For the analysis of glucose and protein turnover radioactive and stable isotope techniques were applied. In burned rats primed constant infusions of 6-[3H]-glucose, 1-[14C]-alanine, 3-[14C]-alanine and U-[14C]-acetate were used to determine whole body glucose turnover, gluconeogenesis from C3-precursors and alanine flux. In septic rats nitrogen balance was calculated after determination of 24-hour-urine nitrogen content measured by micro-Kjeldahl digestion. 24-hour urinary 3-methyl-histidine excretion was analysed by amino acid autoanalyser. In human studies hepatic glucose production and urea synthesis rates were measured using primed continuous infusions of [6,6-d2]-glucose and [2-N15]-urea, respectively. RESULTS: In the first trauma model we demonstrated that hypocaloric xylitol in contrast to glucose significantly reduced hepatic glucose production and gluconeogenesis from C3-carbons. In the septic rat exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated nitrogen retention and lower 3-methyl-histidine excretion. In two studies on surgical intensive care patients we were able to confirm these nitrogen sparing properties of xylitol. Hepatic glucose production and urea synthesis rates were significantly reduced during xylitol infusion after trauma, whereas equicaloric glucose had no effects. In septic patients xylitol led to significant lower lactate concentrations and gluconeogenesis rates than isocaloric glucose. DISCUSSION: In animal as well as in human studies hypocaloric xylitol and the mixture of glucose/xylitol (1:1) were more efficient in preserving body protein than glucose alone. Hepatic gluconeogenesis was significantly reduced when compared to isocaloric glucose. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg BW/d by xylitol. During long-term TPN a glucose/xylitol mixture (1:1) in a dosage of 6 g/kg BW/d is recommended together with amino acids and, if necessary, lipids.

Animals↗
PubMed1993

[New aspects of parenteral nutrition of septic patients].

A major goal of this review article is to show that nutritional physiology in normal man is rather different from patients bearing an inflammatory response. Known nutrients and a variety of energy sources reveal pharmacological actions during such metabolic circumstances. An understand of the pathophysiologic state of sepsis is essential for adequate nutritional support especially in this patient population.

Energy Metabolism↗
PubMed1991

[Artificial feeding].

An infusion rate above 3 g/kg BW per day glucose leads to a reduction of oxidative metabolism of the energy sources glucose, free fatty acids, and exogenous triglycerides. Simultaneously splanchnic lipogenesis is stimulated and visceral protein utilization inhibited. During the 1st to 4th day after trauma Xylitol (3 g/kg BW per day) is superior to glucose with regard to oxidative metabolism of energy sources and stimulation of visceral protein synthesis. A comparable metabolic effect can be achieved by a glucose/xylitol mixture (1:1); (6 g/kg BW per day) during long-term nutrition.

Blood Glucose↗
PubMed1991

[The mechanism of the reduction of protein catabolism following trauma and during sepsis using xylitol].

Total parenteral nutrition (TPN) after trauma and sepsis has two major goals. One is the reduction of enhanced protein catabolism; the second is the avoidance of enhancement of whole-body glucose turnover. Glucose and xylitol differ in their quantitative utilization rate after trauma and sepsis. Maximal glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects with regard to whole-body glucose turnover rate of gluconeogenesis and protein sparing, we conducted two studies using animal models and two clinical studies. METHODS. For the determination of glucose and protein turnover, radioactive and stable isotope techniques were applied. In an animal model a primed constant infusion of 3-H-6-glucose, 14-C-1-alanine and 13-C-3-alanine and 14-C-U-acetate was used to determine total glucose appearance, gluconeogenesis from 3-C-precursors and alanine flux. In the human studies hepatic glucose production was determined by using a primed constant infusion of 6.6-D-2-glucose and urea synthesis rate was determined by a primed constant infusion of 2-N-15-urea. RESULTS. In the first rat model we were able to show that hypocaloric xylitol compared to glucose significantly reduced whole-body glucose turnover from 1741 +/- 232 mumol/h during glucose infusion to 449 +/- 49 mumol/h during xylitol infusion and gluconeogenesis from C-3 carbons form 382 +/- 24 mumol/h during glucose infusion to 155 +/- 39 mumol/h during xylitol infusion after a burn trauma. In a second septic rat model the exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated N-balance from +144 +/- 90 mgN/kg body weight per day during glucose infusion to +699 +/- 80 mgN/kg body weight per day during glucose-xylitol infusion and a reduced 3-methyl-histidine excretion from 7.14 +/- 0.61 mumol/kg body wt. per day during glucose infusion to 4.10 +/- 0.56 mumol/kg per day during glucose-xylitol infusion, respectively. In two studies with surgical intensive care patients we were able to confirm the nitrogen-sparing properties of xylitol infusion, together with amino acids during hypocaloric feeding or during TPN with a glucose/xylitol mixture in a proportion of 1:1. From a basal urea production rate of 9.2 +/- 1.6 mumol/kg min. xylitol led to a significant reduction with 6.4 +/- 1.5 mumol/kg per min. Hepatic glucose production was significantly reduced during xylitol infusion from basal 4.8 +/- 0.6 mg/kg per min to 3.1 +/- 0.7 mg/kg per min, respectively. Equicaloric glucose in a dosage of 3 g/kg per day had no effect. During TPN glucose/xylitol, in a proportion of 1:1 at a total dosage of 0.24 g/kg per h, significantly reduced whole-body glucose turnover, endogenous glucose production and lactate concentrations compared to an isocaloric glucose infusion. DISCUSSION. In animal as well as in human studies hypocaloric xylitol as well as a glucose-xylitol mixture were more efficient in preserving body protein than glucose alone. Whole-body glucose turnover was significantly reduced during hypocaloric xylitol or glucose-xylitol infusion compared to isocaloric glucose infusion. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg body wt. per day using xylitol. During long-term TPN, a glucose-xylitol mixture in a proportion of 1:1 in a dosage of 3 g/kg body wt. per day each is recommended as energy source, together with amino acids and, if necessary, lipids.

Animals↗