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Original article
Adrenomedullin attenuates ventilator-induced lung injury in mice
  1. Holger Christian Müller1,
  2. Martin Witzenrath1,
  3. Thomas Tschernig2,
  4. Birgitt Gutbier1,
  5. Stefan Hippenstiel1,
  6. Ansgar Santel3,
  7. Norbert Suttorp1,
  8. Simone Rosseau1
  1. 1Charité-Universitätsmedizin Berlin, Department of Infectious Diseases and Pulmonary Medicine, Berlin, Germany
  2. 2Saarland University Faculty of Medicine, Institute of Anatomy, Germany
  3. 3Silence Therapeutics AG, Berlin, Germany
  1. Correspondence to Holger C Müller, Charité-Universitätsmedizin Berlin, Department of Infectious Diseases and Pulmonary Medicine, Charitéplatz 1, D-10117 Berlin, Germany; holger.mueller{at}charite.de

Abstract

Background Mechanical ventilation (MV) is a life-saving intervention in acute respiratory failure without any alternative. However, even protective ventilation strategies applying minimal mechanical stress may evoke ventilator-induced lung injury (VILI). Adjuvant pharmacological strategies in addition to lung-protective ventilation to attenuate VILI are lacking. Adrenomedullin exhibited endothelial barrier-stabilising properties in vitro and in vivo.

Methods In untreated mice (female C57/Bl6 mice, 11–15 weeks old) and animals treated with adrenomedullin, lung permeability, local and systemic inflammation and markers of distal organ function were assessed following 2 or 6 h of mechanical ventilation with 100% oxygen and protective or moderately injurious ventilator settings, respectively.

Results Adrenomedullin dramatically reduced lung permeability in VILI in mice, leading to improved oxygenation. Adrenomedullin treatment reduced myosin light chain phosphorylation, attenuated the accumulation of leucocytes in the lung and prevented the increase in lactate and creatinine levels in mice ventilated with high tidal volumes. Moreover, adrenomedullin protected against VILI even when treatment was initiated 2 h after the beginning of mechanical ventilation in a 6 h VILI mouse model.

Conclusion Adjuvant treatment with adrenomedullin may be a promising new pharmacological approach to attenuate VILI.

  • Ventilator-induced lung injury
  • adrenomedullin
  • acute lung injury
  • permeability
  • myosin light chain
  • renal failure
  • microcirculation
  • ARDS
  • pulmonary oedema
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Footnotes

  • Funding Supported in part by grants from the German Research Foundation to MW (OP 86/7-1 and SFB/TR 84, C3 and C6) and SH (HI-789/6-1), and the German Federal Ministry of Education and Research to HCM, SH, NS and SR (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis, PROGRESS).

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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