A new experimental approach to Ventilator-associated Pneumonia: Susceptibility of mice to Pseudomonas Aeruginosa Pneumonia is influenced by Ventilator-Induced Lung Injury

Introduction Ventilator-associated pneumonia (VAP) is one of the most frequently diagnosed nosocomial infections in intensive care units (ICU) and a major cause of patient morbidity and mortality. Pseudomonas aeruginosa (PsA) is a common pathogen causing VAP in patients undergoing mechanical ventilation (MV). MV, normally a life-saving intervention, may exacerbate pre-existing lung injury, a process termed ventilator-induced lung injury (VILI), which is characterized by pulmonary and systemic hyperinflammation as well as increased pulmonary permeability. Whether MV and the associated inflammation have an impact on the development of VAP is not clear, and little is known about the underlying pathomechanisms, which might be partially explained by the lack of suitable experimental models.

Methods We established a new murine model of VAP to explore the influence of MV on the development of PsA pneumonia. Sedated female C57Bl/6J mice were subjected to MV. VILI was induced by high tidal volume ventilation (HVt: 34 ml/kg), and protectively ventilated (LVt; low Vt: 9 ml/kg) animals were used as control. After 4 h, mice were detached from the ventilator and PsA was instilled via the ventilation tube. After infection, sedation was antagonized and the animals were extubated and breathed spontaneously for 24 h. Respiratory function was tested at the start and the end of MV. Lung permeability, inflammatory responses, and bacterial load (CFU – colony forming units) in lung, blood, liver and spleen were analyzed 24 h post infection.

Results HVt MV led to an increased mean airway pressure (Pao) and decreased lung compliance after 4 h of MV. HVt ventilated mice infected with PsA showed enhanced alveolar-capillary permeability, and increased lung and blood leukocyte counts compared to infected LVt ventilated mice. Interestingly the pulmonary and extrapulmonary CFU counts were significantly higher in HVt ventilated animals than in the LVt controls.

Conclusion Mice subjected to VILI (HVt MV) before PsA infection were more compromised by ensuing pneumonia than protectively (LVt) ventilated control mice. This novel murine model of PsA-induced VAP helps to differentiate between effects of preceding as compared to ongoing MV in the development of pneumonia and may thus enable for investigations on the pathophysiology of VAP.