Pre-exposure to mechanical ventilation and endotoxemia increases Pseudomonas aeruginosa growth in lung tissue during experimental porcine pneumonia

BACKGROUND: Immune system suppression during critical care contributes to the risk of acquired bacterial infections with Pseudomonas (P.) aeruginosa. Repeated exposure to endotoxin can attenuate systemic inflammatory cytokine responses. Mechanical ventilation affects the systemic inflammatory response to various stimuli. AIM: To study the effect of pre-exposure to mechanical ventilation with and without endotoxin-induced systemic inflammation on P. aeruginosa growth and wet-to-dry weight measurements on lung tissue and plasma and bronchoalveolar lavage levels of tumor necrosis factor alpha, interleukins 6 and 10. METHODS: Two groups of pigs were exposed to mechanical ventilation for 24 hours before bacterial inoculation and six h of experimental pneumonia (total experimental time 30 h): A(30h+Etx) (n = 6, endotoxin 0.063 μg x kg(-1) x h(-1)) and B(30h) (n = 6, saline). A third group, C(6h) (n = 8), started the experiment at the bacterial inoculation unexposed to endotoxin or mechanical ventilation (total experimental time 6 h). Bacterial inoculation was performed by tracheal instillation of 1x10(11) colony-forming units of P. aeruginosa. Bacterial cultures and wet-to-dry weight ratio analyses were done on lung tissue samples postmortem. Separate group comparisons were done between A(30h+Etx) vs.B(30h) (Inflammation) and B(30h) vs. C(6h) (Ventilation Time) during the bacterial phase of 6 h. RESULTS: P. aeruginosa growth was highest in A(30h+Etx), and lowest in C(6h) (Inflammation and Ventilation Time both p<0.05). Lung wet-to-dry weight ratios were highest in A(30h+Etx) and lowest in B(30h) (Inflammation p<0.01, Ventilation Time p<0.05). C(6h) had the highest TNF-α levels in plasma (Ventilation Time p<0.01). No differences in bronchoalveolar lavage variables between the groups were observed. CONCLUSIONS: Mechanical ventilation and systemic inflammation before the onset of pneumonia increase the growth of P. aeruginosa in lung tissue. The attenuated growth of P. aeruginosa in the non-pre-exposed animals (C(6h)) was associated with a higher systemic TNF-α production elicited from the bacterial challenge.