RT Journal Article
T1 Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
A1 Autilio, Chiara
A1 Echaide Torreguitar, Mercedes
A1 Cruz Rodríguez, Antonio
A1 Hidalgo, A.
A1 Da Silva, E.
A1 De Luca, Daniele
A1 Sørli, Jorid B.
A1 Pérez-Gil, Jesús
AB Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant flms have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purifed porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperaturedependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of flms made of native surfactant. Lipid/protein mixtures designed as models to mimic diferent surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant flms exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more efective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.
PB Nature Research
SN ESSN: 2045-2322
YR 2020
FD 2020-01-12
LK https://hdl.handle.net/20.500.14352/8143
UL https://hdl.handle.net/20.500.14352/8143
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
DS Docta Complutense
RD 17 ago 2024