Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia



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Autilio, Chiara and Echaide Torreguitar, Mercedes and Cruz Rodríguez, Antonio and Hidalgo, A. and Da Silva, E. and De Luca, Daniele and Sørli, Jorid B. and Pérez-Gil, Jesús (2020) Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia. Scientific Reports, 11 (728). pp. 1-14. ISSN ESSN: 2045-2322

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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.

Item Type:Article
Uncontrolled Keywords:Llung surfactant; Hypothermia
Subjects:Medical sciences > Biology > Molecular biology
Medical sciences > Biology > Biochemistry
ID Code:65603
Deposited On:20 May 2021 11:45
Last Modified:31 May 2021 10:18

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