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 ef fects on metabolism in volunteers and possible implications for the us e of sympathomimetics in the critically ill. Design: Descriptive labor atory investigation. Subjects: 7 volunteers. Intervention: Primed cont inuous infusions of stable isotope tracers ([N-15(2)]-urea, [6,6-D2]-g lucose, [methyl-D3]-L-leucine, [N-15]-L-alanine) were used. After isot opic steady state had been reached an infusion of adrenaline (0.1 mug/ kg/min) was administered (4 h). Isotopic enrichment was measured using gas chromatography-mass spectrometry and the corresponding rates of a ppearance were calculated. Measurements and main results: Glucose prod uction 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 t o 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, respectiv ely, 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 (bo th p < 0.05). Alanine flux increased from 3.7 +/- 0.5 to 6.9 +/- 0.9 m umol/kg/min (p < 0.05) after 80 min of adrenergic stimulation. Urea pr oduction slightly decreased from 4.8 +/- 0.9 to 4.3 +/- 0.8 mumol/kg/m in during adrenaline (p < 0.05). Conclusions. Adrenaline induced an in crease in glucose production lasting for longer than 240 min. The decr ease in leucine and KIC flux suggests a reduction in proteolysis, whic h was supported by the decrease in urea production. The increase in al anine flux is therefore most likely due to an increase in de-novo synt hesis. The ammonia donor for alanine synthesis in peripheral tissues a nd the target for ammonia after alanine deamination in the liver remai n to be investigated. These results indicate that adrenaline infusion most probably will not promote already enhanced proteolysis in critica lly ill patients. Gluconeogenesis is an energy consuming process and a n increase may deteriorate hepatic oxygen balance in patients.