Sequential changes in in vivo muscle and liver protein synthesis and plasma and tissue glutamine levels in sepsis in the rat

We have investigated sequential changes in skeletal muscle and hepatic prot ein synthesis following sepsis, and their relationship to changes in circul ating and tissue glutamine concentrations. Male Wistar rats underwent caeca l ligation and puncture (CLP) or sham operation, with starvation, and were killed 24, 72 or 96 h later. A group of non-operated animals were killed at the time of surgery. Protein synthesis was determined using a flooding dos e of L-[4-H-3] phenylalanine, and glutamine concentrations were measured by an enzymic fluorimetric assay. Protein synthesis in gastrocnemius muscle f ell in all groups. Gastrocnemius total protein content was reduced after CL P and at 72 and 96 h after sham operation. After CLP, protein synthesis was lower at 24 h, and total protein content was lower at 72 and 96 h, than in sham-operated animals. CLP was associated with increased liver protein syn thesis at all time points, whereas there was no change after sham operation . Liver protein content did not change after CLP, but was lower at 72 and 9 6 h after sham operation than in non-operated animals. Plasma glutamine con centrations were reduced at 24 h after sham operation, and at 72 and 96 h a fter CLP. Muscle glutamine concentrations were reduced in all groups, with the decrease being greater following CLP than after sham operation. In the liver, glutamine concentrations were unchanged after CLP, but increased aft er sham operation. In rats with sepsis, decreases in muscle protein synthes is and content are associated with markedly reduced muscle glutamine concen trations. Plasma glutamine concentrations are initially maintained, but fal l later. In liver, protein synthesis is increased, while glutamine concentr ations are preserved. These results support a peripheral-to-splanchnic glut amine flux in sepsis.