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Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits
Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Comenius Univ, Jessenius Fac Med Martin, Biomed Ctr Martin, Martin, TN USA;Comenius Univ, Jessenius Fac Med Martin, Dept Physiol, Martin, TN USA.
Swedish Natl Vet Inst, Dept Pathol, Uppsala, Sweden.
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2019 (English)In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, article id 245Article in journal (Refereed) Published
Abstract [en]

AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 20, article id 245
Keywords [en]
ARDS model, Surfactant protein analogues, Synthetic pulmonary surfactant, Lung function
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-398024DOI: 10.1186/s12931-019-1220-xISI: 000495741500002PubMedID: 31694668OAI: oai:DiVA.org:uu-398024DiVA, id: diva2:1375462
Funder
Swedish Heart Lung Foundation, 20170531Swedish Heart Lung Foundation, 20150627Swedish Research Council, K2015-99X-22731-01-4Swedish Research Council, 2014-2408Swedish Research Council Formas, 2015-629VinnovaAvailable from: 2019-12-05 Created: 2019-12-05 Last updated: 2019-12-05Bibliographically approved

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