Document Detail


New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs.
MedLine Citation:
PMID:  23091635     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: 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 P(a)O(2) 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.
CONCLUSIONS: 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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-16
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-23     Completed Date:  2013-03-28     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e47631     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
1,2-Dipalmitoylphosphatidylcholine / administration & dosage,  pharmacology*
Animals
Biological Agents / administration & dosage,  pharmacology
Female
Lung / drug effects*,  pathology,  physiopathology*
Male
Phosphatidylglycerols / administration & dosage,  pharmacology*
Phospholipids / administration & dosage,  pharmacology
Pregnancy
Premature Birth* / drug therapy,  mortality
Pulmonary Surfactant-Associated Protein B / pharmacology
Pulmonary Surfactant-Associated Protein C / pharmacology
Pulmonary Surfactant-Associated Proteins / administration & dosage,  pharmacology*
Pulmonary Surfactants / administration & dosage,  pharmacology*
Sheep
Chemical
Reg. No./Substance:
0/Biological Agents; 0/Phosphatidylglycerols; 0/Phospholipids; 0/Pulmonary Surfactant-Associated Protein B; 0/Pulmonary Surfactant-Associated Protein C; 0/Pulmonary Surfactant-Associated Proteins; 0/Pulmonary Surfactants; 2644-64-6/1,2-Dipalmitoylphosphatidylcholine; KE3U2023NP/poractant alfa
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