New Surfactant with SP-B and C Analogs Gives Survival Benefit after Inactivation in Preterm Lambs

Matthias Seehase, Jennifer J.P. Collins, Elke Kuypers, Reint K. Jellema, Daan R.M.G. Ophelders, Olga L. Ospina, J. Perez-Gil, Federico Bianco, Raffaella Garzia, Roberta Razzetti, Boris W. Kramer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Respiratory distress syndrome in preterm babies is caused by a pulmonary surfactant deficiency, but also by its inactivation due to various conditions, including plasma protein leakage. Surfactant replacement therapy is well established, but clinical observations and in vitro experiments suggested that its efficacy may be impaired by inactivation. A new synthetic surfactant (CHF 5633), containing synthetic surfactant protein B and C analogs, has shown comparable effects on oxygenation in ventilated preterm rabbits versus Poractant alfa, but superior resistance against inactivation in vitro. We hypothesized that CHF 5633 is also resistant to inactivation by serum albumin in vivo. 

Methodology/Principal Findings: 

Nineteen preterm lambs of 127 days gestational age (term = 150 days) received CHF 5633 or Poractant alfa and were ventilated for 48 hours. Ninety minutes after birth, the animals received albumin with CHF 5633 or Poractant alfa. Animals received additional surfactant if PaO2 dropped below 100 mmHg. A pressure volume curve was done post mortem and markers of pulmonary inflammation, surfactant content and biophysiology, and lung histology were assessed. CHF 5633 treatment resulted in improved arterial pH, oxygenation and ventilation efficiency index. The survival rate was significantly higher after CHF 5633 treatment (5/7) than after Poractant alfa (1/8) after 48 hours of ventilation. Biophysical examination of the surfactant recovered from bronchoalveolar lavages revealed that films formed by CHF 5633-treated animals reached low surface tensions in a wider range of compression rates than films from Poractant alfa-treated animals. 


For the first time a synthetic surfactant containing both surfactant protein B and C analogs showed significant benefit over animal derived surfactant in an in vivo model of surfactant inactivation in premature lambs.

Original languageEnglish
Article numbere47631
JournalPLoS ONE
Issue number10
Publication statusPublished - 16 Oct 2012
Externally publishedYes

Bibliographical note


BWK is supported by a VENI grant (No. BWK 016.096.141) from the Dutch Research Council (NWO). OLO and JPG are supported by grants from the
Spanish Ministry of Economy and Competitivity (BIO2009–09694, CSD2007–00010) and Community of Madrid (S2009MAT-1507). This study was funded by Chiesi
Pharmaceutici SpA (Parma, Italy). Preparations of CHF 5633 synthetic surfactant and CurosurfH were also supplied by Chiesi Pharmaceutici SpA. FB, RR and RG
participated in the interpretation of the data and review of the manuscript, but otherwise the funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.


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