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

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 x 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 x 10(12) 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 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).

CONCLUSIONS

Pharmacological inhibition of PARP reduces gut inflammation and may limit bacterial translocation.