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Ventilator-Induced Lung Injury Increases the Susceptibility of Mice to Pseudomonas Aeruginosa Pneumonia
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A5129 - Ventilator-Induced Lung Injury Increases the Susceptibility of Mice to Pseudomonas Aeruginosa Pneumonia
Author Block: M. Felten, E. Letsiou, H. C. Muller-Redetzky, N. W. Suttorp, M. Witzenrath; Department of Infectious Diseases and Pulmonary Medicine, Charite, Berlin, Germany.
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 generally little is known about the underlying pathomechanisms of VAP, 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 (8-12 weeks) 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 and breathed spontaneously for 24h. 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 24h post infection.
Results. HVt MV led to a significantly 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 LVt ventilated mice. The pulmonary bacterial load in the HVt group was higher (2,5x105CFUs/lung) than in the LVt group (2x102CFUs/lung), but the difference was not significant. Interestingly, extrapulmonary CFU counts were significantly higher in HVt ventilated animals.
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.
Author Block: M. Felten, E. Letsiou, H. C. Muller-Redetzky, N. W. Suttorp, M. Witzenrath; Department of Infectious Diseases and Pulmonary Medicine, Charite, Berlin, Germany.
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 generally little is known about the underlying pathomechanisms of VAP, 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 (8-12 weeks) 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 and breathed spontaneously for 24h. 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 24h post infection.
Results. HVt MV led to a significantly 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 LVt ventilated mice. The pulmonary bacterial load in the HVt group was higher (2,5x105CFUs/lung) than in the LVt group (2x102CFUs/lung), but the difference was not significant. Interestingly, extrapulmonary CFU counts were significantly higher in HVt ventilated animals.
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.
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