Glutathione (GSH) Absolute Synthesis Rates (ASR) of Multiple Organs in a Pseudomonas aeroginosa (PM) induced Hyperdynamic Sepsis Pig Model Conference Paper uri icon

abstract

  • RationaleSepsis is characterized by a severe redox imbalance. GSH plays a major role in the cellular defense against oxidative and nitrosative stress. It remains unclear whether the GSH defense capacity of tissues is affected differently at an early stage of severe sepsis. Therefore we measured the early response in GSH synthesis of the gut, muscle, liver, and lung in an acute live bacteria (PM) induced hyperdynamic severe sepsis catheterized pig model.MethodWe studied GSHASR in 13 pigs (25 kg) with intravenous PM induced hyperdynamic sepsis and 9 healthy controls, using primed, constant and continuous infusion of Glycine (113C) stable isotope in a conscious postabsorptive state. Between 14 and 18 hours after start of the sepsis induction, we collected jejunal mucosa biopsies and erythrocytes, and at eighteen hours we obtained jejunum, jejunal mucosa scraping, ileum, liver, muscle and lung tissue. Enrichments of precursor pools and incorporated glycine in GSH were analyzed by LCMS/MS. Data are mean (SE) (in mol/kg/h); ANOVA and unpaired ttests were done by GraphPad Prism.ResultsWe found decreased values for GSHASR 14 to18h after sepsis induction in jejunal mucosa biopsies (p=0.032) but not in erythrocytes. At t=18 h, we found lower ASR in sepsis in jejunum (37.3 (5.5) vs 23.7 (2.6), p=0.021) and jejunal mucosa scrapings (45.0 (6.2) vs. 28.9 (3.9), p=0.033). No changes in GSHASR in ileum, liver and muscle were found but GSHASR tended to be higher in the lung (20.2 (3.0) vs 26.9 (2.2), p=0.086).ConclusionIn acute severe sepsis in the pig, the early defense capacity for oxidative stress is compromised in the mucosa of the jejunum, but not in the muscle, liver, lung, ileum and erythrocytes. We hypothesize that restoring the jejunal GSH defense capacity will attenuate the early sepsis induced gut dysfunction.Support or Funding InformationThis study was supported by NIH R01GM084447 and S10RR027047

published proceedings

  • FASEB JOURNAL

author list (cited authors)

  • Ten Have, G. A., Engelen, M. P., Wolfe, R. R., & Deutz, N. E.

citation count

  • 0

complete list of authors

  • Ten Have, Gabriella A||Engelen, Marielle P||Wolfe, Robert R||Deutz, Nicolaas E

publication date

  • April 2016

publisher