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DOI: 10.1055/s-0032-1302605
Ventilator-induced lung injury in severe pneumococcal pneumonia: protection by Adrenomedullin
Ventilator-induced lung injury (VILI) contributes to mortality in ARDS. Particularly preinjured lungs may be susceptible to VILI despite lung protective ventilation. We previously observed protection against VILI by therapeutic use of the endogenous peptide Adrenomedullin (AM) in addition to lung protective ventilation in mice. The current study analyzed the impact of mechanical ventilation (MV) on lung injury, pulmonary and systemic inflammation and bacterial burden in established pneumonia. Further, AM was used therapeutically to limit VILI in a clinically relevant murine model.
S. pneumoniae infected individuals were subjected to MV 24h after infection. Mice were ventilated with a tidal volume of 12ml/kg for 6h. AM was continuously infused starting with the onset of MV. Pulmonary permeability, oxygenation, lung mechanics, cytokines in lung and plasma, lung and blood leukocytes, and bacterial burden in lung, blood and spleen were assessed. Pulmonary expression of AM and its receptor complexes of CRLR and RAMP 1–3 were studied by immunoflourescence and qPCR analyses.
In severe pneumonia, MV aggravated lung injury indicated by increased pulmonary vascular permeability, oxygenation failure and worsening of lung mechanics. MV dramatically increased lung and blood cytokine levels in pneumonia, while lung leukocyte counts in pneumonia were not affected by MV. In infected mice MV induced leukocytopenia. Lung and blood bacterial burden was not affected by MV. MV and pneumonia increased lung AM expression. RAMP 1–3 were upregulated in pneumonia but MV reduced its expression. Exogenous AM protected against MV induced pulmonary hyperpermeability and deterioration of lung mechanics in pneumonia. AM did not alter inflammation.
In conclusion, MV aggravated lung injury in pneumococcal pneumonia. MV may pave the way for progression of pneumonia towards sepsis. AM may be a promising adjuvant therapy to limit VILI in pneumonia induced lung injury.
Supported by SFB/TR84 -C6+Z2, PROGRESS