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, Csaba Szabo, Jean Louis Vincent

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 2005
Externally publishedYes

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Pseudomonas aeruginosa
Sepsis
Pneumonia
Wounds and Injuries
Poly(ADP-ribose) Polymerases
Poly(ADP-ribose) Polymerase Inhibitors
Buffers
Phosphates
Bacterial Translocation
Peroxynitrous Acid
DNA Breaks
Superior Mesenteric Artery
Septic Shock
Sodium Chloride
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
Lactic Acid
Pharmacology
Rabbits
Inflammation
Weights and Measures

Keywords

  • Bacterial translocation
  • Gut inflammation
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Surgery

Cite this

Lobo, S. M., Orrico, S. R. P., Queiroz, M. M., Cunrath, G. S., Chibeni, G. S. A., Contrin, L. M., ... 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

Pneumonia-induced sepsis and gut injury : Effects of a poly-(ADP-ribose) polymerase inhibitor. / Lobo, Suzana M.; Orrico, Susana R Perez; Queiroz, Márcio M.; Cunrath, Geni S.; Chibeni, Gisela S A; Contrin, Ligia M.; Cury, Patricia M.; De Almeida Burdmann, Emanuel; De Oliveira Machado, Antonia M.; Togni, Paulo; De Backer, Daniel; Preiser, Jean Charles; Szabo, Csaba; Vincent, Jean Louis.

In: Journal of Surgical Research, Vol. 129, No. 2, 12.2005, p. 292-297.

Research output: Contribution to journalArticle

Lobo, SM, Orrico, SRP, Queiroz, MM, Cunrath, GS, Chibeni, GSA, Contrin, LM, Cury, PM, De Almeida Burdmann, E, De Oliveira Machado, AM, Togni, P, De Backer, D, Preiser, JC, Szabo, C & Vincent, JL 2005, 'Pneumonia-induced sepsis and gut injury: Effects of a poly-(ADP-ribose) polymerase inhibitor', Journal of Surgical Research, vol. 129, no. 2, pp. 292-297. https://doi.org/10.1016/j.jss.2005.05.018
Lobo, Suzana M. ; Orrico, Susana R Perez ; Queiroz, Márcio M. ; Cunrath, Geni S. ; Chibeni, Gisela S A ; Contrin, Ligia M. ; Cury, Patricia M. ; De Almeida Burdmann, Emanuel ; De Oliveira Machado, Antonia M. ; Togni, Paulo ; De Backer, Daniel ; Preiser, Jean Charles ; Szabo, Csaba ; Vincent, Jean Louis. / Pneumonia-induced sepsis and gut injury : Effects of a poly-(ADP-ribose) polymerase inhibitor. In: Journal of Surgical Research. 2005 ; Vol. 129, No. 2. pp. 292-297.
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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.",
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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 - Szabo, Csaba

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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