Document Detail

A synthetic surfactant based on a poly-Leu SP-C analog and phospholipids: effects on tidal volumes and lung gas volumes in ventilated immature newborn rabbits.
MedLine Citation:
PMID:  12897027     Owner:  NLM     Status:  MEDLINE    
Available surfactants for treatment of respiratory distress syndrome in newborn infants are derived from animal lungs, which limits supply and poses a danger of propagating infectious material. Poly-Val-->poly-Leu analogs of surfactant protein (SP)-C can be synthesized in large quantities and exhibit surface activity similar to SP-C. Here, activity of synthetic surfactants containing a poly-Leu SP-C analog (SP-C33) was evaluated in ventilated premature newborn rabbits. Treatment with 2.5 ml/kg body wt of 2% (wt/wt) SP-C33 in 1,2-dipalmitoyl-sn-3-glycero phosphoryl choline (DPPC)-1-palmitoyl-2-oleoyl-sn-3-glycero phosphoryl choline (POPC)-1-palmitoyl-2-oleoyl-sn-3-glycero phosphoryl glycerol (POPG), 68:0:31, 68:11:20, or 68:16:15 (wt/wt/wt) suspended at 80 mg/ml gave tidal volumes (Vt) of 20-25 ml/kg body wt, with an insufflation pressure of 25 cmH2O and no positive end-expiratory pressure (PEEP), comparable to the Vt for animals treated with the porcine surfactant Curosurf. Nontreated littermates had a Vt of approximately 2 ml/kg body wt. The Vt for SP-C33 in DPPC-egg phosphatidylglycerol-palmitic acid [68:22:9 (wt/wt/wt)], DPPC-POPG-palmitic acid [68:22:9 (wt/wt/wt)], and DPPC-POPC-POPG [6:2:2 (wt/wt/wt)] was 15-20 ml/kg body wt. Histological examination of lungs from animals treated with SP-C33-based surfactants showed incomplete, usually patchy air expansion of alveolar spaces associated with only mild airway epithelial damage. Lung gas volume after 30 min of mechanical ventilation were more than threefold larger in animals treated with Curosurf than in those receiving SP-C33 in DPPC-POPC-POPG, 68:11:20. This difference could be largely counterbalanced by ventilation with PEEP (3-4 cmH2O). An artificial surfactant based on SP-C33 improves Vt in immature newborn animals ventilated with standardized peak pressure but requires PEEP to build up adequate lung gas volumes.
Jan Johansson; Margareta Some; Britt-Marie Linderholm; Andreas Almlén; Tore Curstedt; Bengt Robertson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-08-01
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  95     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-13     Completed Date:  2004-06-15     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2055-63     Citation Subset:  IM    
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Amino Acid Sequence
Animals, Newborn
Infant, Newborn
Lung / drug effects,  physiology
Molecular Sequence Data
Phosphatidylcholines / pharmacology*
Phosphatidylglycerols / pharmacology*
Protein Structure, Tertiary
Pulmonary Surfactant-Associated Protein C / analogs & derivatives*,  chemistry
Respiration, Artificial
Respiratory Distress Syndrome, Newborn / drug therapy*,  physiopathology
Tidal Volume / drug effects*
Reg. No./Substance:
0/Phosphatidylcholines; 0/Phosphatidylglycerols; 0/Pulmonary Surfactant-Associated Protein C; 81490-05-3/1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; TE895536Y5/1-palmitoyl-2-oleoylphosphatidylcholine

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