Protein metabolism in leg muscle following an endotoxin injection in healthy volunteers

Rokhsareh F. Vesali , Norbert Cibicek , Towe Jakobsson , Maria Klaude , Jan Wernerman , Olav Rooyackers (1)

1 Anaesthesiology and Intensive Care

The human endotoxin model has been used to study the early phase of sepsis. The aim of the present study was to assess leg muscle protein kinetics after an endotoxin challenge given to healthy human volunteers. Six healthy male subjects were studied in the post-absorptive state before and during 4 hours following an intravenous endotoxin bolus (4 ng / kg body weight). Primed continuous infusion of [2H5]phenylalanine and [2H3]3-methylhistidine in combination with sampling from artery, femoral vein and muscle tissue were used to assess leg muscle protein kinetics. Both 2 and 3-compartment models were used to calculate protein kinetics. In addition 26S proteasome activity and protein ubiquitination were assessed. Results showed an increased net release of phenylalanine from the leg following the endotoxin challenge. However, this phenylalanine originates from the free intracellular pool and not from protein. Net protein balance was unchanged, whereas both protein synthesis and breakdown were decreased. Degradation rates of contractile proteins were not affected by endotoxin as indicated by an unchanged rate of appearance of 3-methylhistidine from leg muscle. Also proteasome activity and protein ubiquitination were unaffected by endotoxemia. Intravenous endotoxin administration to healthy volunteers resulted in an increased release of free phenylalanine from skeletal muscle whereas protein balance was unaffected. Both protein synthesis and breakdown were decreased to a similar extent.

Mots clés: Medicine

Rokhsareh F. Vesali, Norbert Cibicek, Towe Jakobsson, Maria Klaude, Jan Wernerman, et al.. Protein metabolism in leg muscle following an endotoxin injection in healthy volunteers. Clinical Science, 2009, 118 (6), pp.421-427. ⟨10.1042/CS20090332⟩. ⟨hal-00546865⟩