Ventilator-Induced Lung Injury Increases Systemic Inflammation in Murine Pseudomonas Aeruginosa Pneumonia
European Respiratory Journal(2019)
摘要
Introduction: Ventilator-associated pneumonia (VAP) is a major cause of nosocomial infections in intensive care units (ICU), leading to increased patient morbidity and mortality. Due to the lack of suitable experimental models, little is known about pathomechanisms of VAP. Methods: We established a new murine model of VAP with Pseudomonas aeruginosa (PsA) to explore the influence of MV on the development of PsA pneumonia. C57Bl/6J mice were subjected to MV. VILI was induced by high tidal volume ventilation (HVt: 34ml/kg), and protectively ventilated (LVt; low Vt: 9ml/kg) animals were used as control. After 4h, mice were detached from the ventilator and PsA was instilled via the ventilation tube. After infection, sedation was antagonized and the animals were extubated, breathing spontaneously for 24h. Respiratory function was tested at the start and the end of MV. Lung permeability, inflammatory responses, histology and bacterial load in lung, blood, liver and spleen were analyzed 24h post infection. Results: HVt MV led to an increased mean airway pressure (Pao) and decreased lung compliance after 4h 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 may enable for investigations on the pathophysiology of VAP.
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