title: Glucose and urea production and leucine, ketoisocaproate and alanine fluxes at supraphysiological plasma adrenaline concentrations in volunteers.
abstract: 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.
  
  
  METHODS
  Descriptive laboratory investigation.
  
  
  METHODS
  7 volunteers.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Universitätsklinik für Anästhesiologie, Ulm, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Ensinger
authors.forename: K
authors.initials: K
authors.lastname: Träger
authors.forename: W
authors.initials: W
authors.lastname: Geisser
authors.forename: T
authors.initials: T
authors.lastname: Anhäupl
authors.forename: F W
authors.initials: FW
authors.lastname: Ahnefeld
authors.forename: J
authors.initials: J
authors.lastname: Vogt
authors.forename: M
authors.initials: M
authors.lastname: Georgieff
mesh_terms: D000328:Adult; D000409:Alanine / Q000187:drug effects* / Q000378:metabolism*; D000596:Amino Acids / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D002208:Caproates / Q000378:metabolism*; D016638:Critical Illness; D004837:Epinephrine / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007651:Keto Acids / Q000378:metabolism*; D007930:Leucine / Q000187:drug effects* / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D010101:Oxygen Consumption / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D013997:Time Factors; D014508:Urea / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D002096:C-Peptide; D002208:Caproates; D007328:Insulin; D007651:Keto Acids; D011506:Proteins; C013082:alpha-ketoisocaproic acid; D014508:Urea; D005934:Glucagon; D007930:Leucine; D000409:Alanine; D004837:Epinephrine