Inhibition of jejunal protein synthesis and breakdown in Pseudomonas aeruginosa-induced sepsis pig model

Abstract

Maintenance of gut integrity has long been rec-ognized as crucial for survival in sepsis, but alterations in protein metabolism have not previously been documented. Therefore, in the present study, we measured in a Pseudomonas aeruginosa-induced porcine sepsis model fractional protein synthesis (FSR) and breakdown rates (FBR) in jejunal mucosa in a fasted, conscious state. FSR was measured by the incorporation rate of stable tracer amino acid (L-[ring-13C6]phenylalanine) into tissue protein. FBR was determined using the relation between blood arterial enrichment and intracellular enrichment of phenylalanine in consecutive mucosal biopsies after a pulse of L-[15N]phenylalanine. Additionally, we determined the FSR in jejunum, ileum, liver, muscle, and lung tissue. We found in this sham-controlled acute sepsis pig model (control: n = 9; sepsis: n = 13) that jejunal mucosal protein turnover is reduced with both decreased FSR (control: 3.29 ± 0.22; sepsis: 2.32 ± 0.12%/h, P = 0.0008) and FBR (control: 0.72 ± 0.12; sepsis: 0.34 ± 0.04%/h, P = 0.006). We also found that FSR was unchanged in ileum and muscle, whereas it was higher in the liver (control: 0.87 ± 0.05; sepsis: 1.05 ± 0.06%/h, P = 0.041). Our data, obtained with a translational acute sepsis model, suggest that jejunal mucosal protein metabolism is diminished in acute sepsis. Comparison with other tissues indicates that the most serious acute metabolic changes in sepsis occur in the jejunum rather than the muscle. NEW & NOTEWORTHY In a highly translational acute sepsis model, presented data suggest that jejunal mucosal protein metabolism is diminished in acute sepsis, even if the origin of the sepsis is not located in the gut. Comparison with other tissues indicates that the most serious acute changes in the protein synthesis rates in sepsis occur in the gut rather than the muscle. Therefore, we hypothesize that preventing a compromised gut is critical to maintain gut function during sepsis.