Pneumonia-induced sepsis and gut injury: Effects of a poly-(ADP-ribose) polymerase inhibitor

Suzana M. Lobo, Susana R.Perez Orrico, Márcio M. Queiroz, Geni S. Cunrath, Gisela S.A. Chibeni, Ligia M. Contrin, Patricia M. Cury, Emanuel De Almeida Burdmann, Antonia M. De Oliveira Machado, Paulo Togni, Daniel De Backer, Jean Charles Preiser, Czaba Szabó, Jean Louis Vincent

    Research output: Contribution to journalArticle

    19 Scopus citations

    Abstract

    Background. Pseudomonas aeruginosa is commonly associated with nosocomial pneumonia. Ileal mucosal injury may be induced by severe lung infection. During septic shock, peroxynitrite-mediated DNA strand-breaks activate the enzyme poly-(ADP)-ribose polymerase (PARP) resulting in cellular energetic suppression and cell dysfunction. The aim of this study was to determine whether gut injury could be demonstrated in sepsis induced by P. aeruginosa and the effects of a PARP inhibitor (PJ34) on the associated gut injury. Materials and Methods. After baseline measurements, 20 rabbits were randomized into three groups: Sham (n = 5): transtracheally inoculated (TI) with 2 ml of phosphate buffer solution (PBS); P. aeruginosa + saline (n = 8), TI with 4 × 1012 CFU/ml of P. aeruginosa in 2 ml/kg of PBS + i.v. saline; and P. aeruginosa + PJ34 (n = 7), TI with 4 × 1012 CFU/ml of P. aeruginosa and i.v. treatment with PJ34. Results. P. aeruginosa caused a hyperdynamic response with increased blood flow also in the superior mesenteric artery. No significant differences were found in luminal gut lactate concentrations or PCO2-gap between groups. Histological specimens showed moderate or diffuse alveolar infiltrate in the P. aeruginosa + saline group (6/8) and in the P. aeruginosa + PJ34 group (6/7). Gut wet-to-dry weight ratio was significantly higher in the P. aeruginosa + saline group than in Shams (7.5 ± 0.8 versus 6.4 ± 0.7, P < 0.05) and significantly lower in the P. aeruginosa + PJ34 group (6.1 + 0.5, P < 0.05 versus the other groups). Blood cultures were positive in 1/5 (Sham), 8/8 (P. aeruginosa + saline group) and 4/7 (P. aeruginosa + PJ34 group) (RR 0.57 CI 95% 0.30+1.08). Conclusions. Pharmacological inhibition of PARP reduces gut inflammation and may limit bacterial translocation.

    Original languageEnglish (US)
    Pages (from-to)292-297
    Number of pages6
    JournalJournal of Surgical Research
    Volume129
    Issue number2
    DOIs
    StatePublished - Dec 1 2005

    Keywords

    • Bacterial translocation
    • Gut inflammation
    • Pseudomonas aeruginosa

    ASJC Scopus subject areas

    • Surgery

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  • Cite this

    Lobo, S. M., Orrico, S. R. P., Queiroz, M. M., Cunrath, G. S., Chibeni, G. S. A., Contrin, L. M., Cury, P. M., De Almeida Burdmann, E., De Oliveira Machado, A. M., Togni, P., De Backer, D., Preiser, J. C., Szabó, C., & Vincent, J. L. (2005). Pneumonia-induced sepsis and gut injury: Effects of a poly-(ADP-ribose) polymerase inhibitor. Journal of Surgical Research, 129(2), 292-297. https://doi.org/10.1016/j.jss.2005.05.018