Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits.
BACKGROUND
Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure.


OBJECTIVE
To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue.


METHODS
Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined.


RESULTS
Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8-9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3-4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15-17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes.


CONCLUSIONS
The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS.
Almlén
Andreas
A
Department of Molecular Medicine and Surgery, Section of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Walther
Frans J
FJ
Waring
Alan J
AJ
Robertson
Bengt
B
Johansson
Jan
J
Curstedt
Tore
T
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use; D047928:Premature Birth; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry / Q000627:therapeutic use*; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry / Q000627:therapeutic use*; D011817:Rabbits; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000628:therapy; D013501:Surface-Active Agents / Q000737:chemistry / Q000627:therapeutic use*; D013990:Tidal Volume / Q000187:drug effects
D010455:Peptides; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D013501:Surface-Active Agents