1. Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin
- Author
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Michael D. Menger, Norbert Weissmann, Olivia Kershaw, Thomas Tschernig, Stefan Hippenstiel, Martin Witzenrath, Wolfgang Kummer, Daniel Will, Uwe Pfeil, Holger Müller-Redetzky, Achim D. Gruber, Norbert Suttorp, Renate Paddenberg, and Katherina Hellwig
- Subjects
medicine.medical_specialty ,ARDS ,medicine.medical_treatment ,Ventilator-Induced Lung Injury ,Lung injury ,Critical Care and Intensive Care Medicine ,Gastroenterology ,Sepsis ,Mice ,Adrenomedullin ,Leukocytopenia ,Internal medicine ,medicine ,Animals ,Mechanical ventilation ,Lung ,business.industry ,Research ,respiratory system ,Pneumonia, Pneumococcal ,medicine.disease ,Respiration, Artificial ,respiratory tract diseases ,Bronchodilator Agents ,Mice, Inbred C57BL ,Pneumonia ,medicine.anatomical_structure ,Anesthesia ,Pneumococcal pneumonia ,Commentary ,Female ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Introduction Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. Methods We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. Results In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1–3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p
- Published
- 2014