TY - JOUR
T1 - Protective effects of aerosolized pulmonary surfactant powder in a model of ventilator-induced lung injury
AU - Daniher, Derek
AU - McCaig, Lynda
AU - Ye, Yuqing
AU - Veldhuizen, Ruud
AU - Lewis, James
AU - Ma, Yingliang
AU - Zhu, Jesse
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/6/15
Y1 - 2020/6/15
N2 - Mechanical ventilation may contribute to the impairment of the pulmonary surfactant system, which is one of the mechanisms leading to the progression of acute lung injury. To investigate the potential protective effects of pulmonary surfactant in a rat model of ventilator-induced lung injury, the surfactant powder was aerosolized using an in-house made device designed to deliver the aerosolized powder to the inspiratory line of a rodent ventilator circuit. Rats were randomized to (i) administration of aerosolized recombinant surfactant protein C based pulmonary surfactant, (ii) intratracheally instillation of the same surfactant re-constituted in saline, and (iii) no treatment. Animals were monitored during 2 h of high-tidal volume mechanical ventilation, after which rats were sacrificed, and further analysis of lung mechanics and surfactant function were completed. Blood gas measurements during ventilation showed extended maintenance of oxygen levels above 400 mmHg in aerosol treated animals over non-treated and instilled groups, while total protein analysis showed reduced levels in the aerosol compared to non-treated groups. Dynamic captive bubble surface tension measurements showed the activity of surfactant recovered from aerosol treated animals is maintained below 1 mN/m. The prophylactic treatment of aerosolized surfactant powder reduced the severity of lung injury in this model.
AB - Mechanical ventilation may contribute to the impairment of the pulmonary surfactant system, which is one of the mechanisms leading to the progression of acute lung injury. To investigate the potential protective effects of pulmonary surfactant in a rat model of ventilator-induced lung injury, the surfactant powder was aerosolized using an in-house made device designed to deliver the aerosolized powder to the inspiratory line of a rodent ventilator circuit. Rats were randomized to (i) administration of aerosolized recombinant surfactant protein C based pulmonary surfactant, (ii) intratracheally instillation of the same surfactant re-constituted in saline, and (iii) no treatment. Animals were monitored during 2 h of high-tidal volume mechanical ventilation, after which rats were sacrificed, and further analysis of lung mechanics and surfactant function were completed. Blood gas measurements during ventilation showed extended maintenance of oxygen levels above 400 mmHg in aerosol treated animals over non-treated and instilled groups, while total protein analysis showed reduced levels in the aerosol compared to non-treated groups. Dynamic captive bubble surface tension measurements showed the activity of surfactant recovered from aerosol treated animals is maintained below 1 mN/m. The prophylactic treatment of aerosolized surfactant powder reduced the severity of lung injury in this model.
KW - Aerosol
KW - Dry powder inhaler
KW - Mechanical ventilation
KW - Pulmonary surfactant
UR - http://www.scopus.com/inward/record.url?scp=85083862318&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2020.119359
DO - 10.1016/j.ijpharm.2020.119359
M3 - Article
C2 - 32334066
AN - SCOPUS:85083862318
SN - 0378-5173
VL - 583
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 119359
ER -