TY - JOUR
T1 - Pneumonia-induced sepsis and gut injury
T2 - Effects of a poly-(ADP-ribose) polymerase inhibitor
AU - Lobo, Suzana M.
AU - Orrico, Susana R.Perez
AU - Queiroz, Márcio M.
AU - Cunrath, Geni S.
AU - Chibeni, Gisela S.A.
AU - Contrin, Ligia M.
AU - Cury, Patricia M.
AU - De Almeida Burdmann, Emanuel
AU - De Oliveira Machado, Antonia M.
AU - Togni, Paulo
AU - De Backer, Daniel
AU - Preiser, Jean Charles
AU - Szabó, Czaba
AU - Vincent, Jean Louis
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
KW - Bacterial translocation
KW - Gut inflammation
KW - Pseudomonas aeruginosa
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U2 - 10.1016/j.jss.2005.05.018
DO - 10.1016/j.jss.2005.05.018
M3 - Article
C2 - 16139303
AN - SCOPUS:29144480267
SN - 0022-4804
VL - 129
SP - 292
EP - 297
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -