Inhaled hydrogen sulfide protects against ventilator-induced lung injury.
BACKGROUND
Mechanical ventilation still causes an unacceptably high rate of morbidity and mortality because of ventilator-induced lung injury (VILI). Therefore, new therapeutic strategies are needed to treat VILI. Hydrogen sulfide can induce hypothermia and suspended animation-like states in mice. Hydrogen sulfide can also confer antiinflammatory and antiapoptotic effects. This study investigates the organ-protective effects of inhaled hydrogen sulfide during mechanical ventilation.


METHODS
Mice were ventilated with a tidal volume of 12 ml/kg body weight for 6 h with synthetic air in the absence or presence of hydrogen sulfide (80 parts per million) and, in a second series, at either mild hypothermia or normothermia. Staining of lung sections determined the degree of lung damage by VILI score and apoptotic cells. Bronchoalveolar lavage fluid was analyzed for the cytokines interleukin-1beta and macrophage inflammatory protein-1beta and for neutrophil accumulation. Heme oxygenase-1 and heat shock protein 70 expression were assessed in the lung tissue by Western immunoblot analysis.


RESULTS
Mechanical ventilation at both hypothermia and normothermia led to a profound development of VILI, characterized by pulmonary edema, increased apoptosis, cytokine release, neutrophil recruitment, and up-regulation of the stress proteins such as heme oxygenase-1 and heat shock protein 70. In contrast, the application of hydrogen sulfide during ventilation at either mild hypothermia or normothermia prevented edema formation, apoptosis, proinflammatory cytokine production, neutrophil accumulation, and inhibited heme oxygenase-1 expression.


CONCLUSIONS
Inhalation of hydrogen sulfide during mechanical ventilation protects against VILI by the inhibition of inflammatory and apoptotic responses. Hydrogen sulfide confers lung protection independently of its ability to induce mild hypothermia during ventilation.
Faller
Simone
S
Department of Anesthesiology and Critical Care Medicine, University Hospital Freiburg, Freiburg, Germany. alexander.hoetzel@uniklinik-freiburg.de
Ryter
Stefan W
SW
Choi
Augustine M K
AM
Loop
Torsten
T
Schmidt
René
R
Hoetzel
Alexander
A
D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D007035:Hypothermia / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*
D015415:Biomarkers; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D051547:Heme Oxygenase-1; D006862:Hydrogen Sulfide