Pneumonia-Induced Sepsis and Gut Injury: Effects of a Poly-(ADP-Ribose) Polymerase Inhibitor

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...

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Published in:	The Journal of surgical research Vol. 129; no. 2; pp. 292 - 297
Main Authors:	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, Szabó, Czaba, Vincent, Jean-Louis
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-12-2005 Elsevier
Subjects:	Animals Aorta Bacterial diseases Bacterial sepsis bacterial translocation Biological and medical sciences Blood Pressure Enteritis - drug therapy Enteritis - microbiology Enzyme Inhibitors - pharmacology General aspects gut inflammation Human bacterial diseases Infectious diseases Intestines - blood supply Intestines - microbiology Intestines - pathology Medical sciences Mesenteric Artery, Superior Phenanthrenes - pharmacology Pneumonia, Bacterial - complications Pneumonia, Bacterial - drug therapy Pneumonia, Bacterial - microbiology Poly(ADP-ribose) Polymerase Inhibitors Pseudomonas aeruginosa Pseudomonas aeruginosa - isolation & purification Pseudomonas Infections - drug therapy Pseudomonas Infections - etiology Rabbits Regional Blood Flow Sepsis - drug therapy Sepsis - microbiology Specific Pathogen-Free Organisms Trachea Pseudomonas aeruginosa bacterial translocation gut inflammation Chromosomal aberration Pseudomonadales Pneumonia ADP Sepsis syndrome Ribose Surgery Bacteria Pseudomonadaceae Chromosome translocation Lung disease Respiratory disease Gut Inflammation Bacteremia Infection Medicine Treatment Bacteriosis Cytogenetics Abnormal chromosome Inhibitor Lesion
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Summary:	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. 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 × 10 12 CFU/ml of P. aeruginosa in 2 ml/kg of PBS + i.v. saline; and P. aeruginosa + PJ34 ( n = 7), TI with 4 × 10 12 CFU/ml of P. aeruginosa and i.v. treatment with PJ34. 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 PCO 2-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). Pharmacological inhibition of PARP reduces gut inflammation and may limit bacterial translocation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-4804 1095-8673
DOI:	10.1016/j.jss.2005.05.018