RT Journal Article
SR Electronic
T1 Adrenomedullin attenuates ventilator-induced lung injury in mice
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 1077
OP 1084
DO 10.1136/thx.2010.135996
VO 65
IS 12
A1 Holger Christian Müller
A1 Martin Witzenrath
A1 Thomas Tschernig
A1 Birgitt Gutbier
A1 Stefan Hippenstiel
A1 Ansgar Santel
A1 Norbert Suttorp
A1 Simone Rosseau
YR 2010
UL http://thorax.bmj.com/content/65/12/1077.abstract
AB 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.