Surfactant with SP-B and SP-C analogues improves lung function in surfactant-deficient rats.
The use of mammalian lung surfactant extracts has sharply reduced mortality and morbidity from respiratory distress syndrome in premature infants. Synthesis of surfactant protein B and C (SP-B and SP-C) analogues may lead the way to a synthetic surfactant preparation. Dimeric SP-B(1-25) (dSP-B(1-25)) is based on the N-terminal domain of human SP-B and SP-Cfc is a modified human SP-C in which a single phenylalanine is substituted for a palmitoylated cysteine residue in the N-terminal segment (Phe-4 > Cys-4 variant). We tested the effects of synthetic surfactants with 1 or 2% dSP-B(1-25) and 1% SP-Cfc on lung function in surfactant-deficient rats. Four experimental surfactant preparations were prepared by mixing 1% dSP-B(1-25), 2% dSP-B(1-25), 1% dSP-B(1-25) +1% SP-Cfc, and 2% dSP-B(1-25) +1% SP-Cfc with phospholipids (PL). PL and Survanta, a bovine lung extract, were controls. Groups of 8 rats were ventilated, lavaged until surfactant deficiency, and treated with 100 mg/kg surfactant. Arterial blood gas values and dynamic compliance were measured every 15 min and after 2 h of ventilation, the rats were killed and pressure-volume curves performed. Oxygenation improved quickly after instillation of surfactant with synthetic peptides and Survanta. Oxygenation and lung volumes were consistently higher in the 2% than in the 1% dSP-B(1-25) groups. Addition of 1% SP-Cfc to the synthetic surfactants further improved oxygenation and lung volume, but to a lesser extent than increasing the dSP-B(1-25) content from 1 to 2%. These data indicate that improvements in oxygenation and lung volume in lavaged rats are dependent on the concentration of dSP-B(1-25) in the surfactant preparation and that the presence of SP-Cfc has a relative minor effect on these parameters.
Walther
Frans J
FJ
Harbor-University of California Los Angeles Research & Education Institute, Torrance, Calif 90502, USA. fjwalther@aol.com
Hernández-Juviel
José M
JM
Mercado
Pamela E
PE
Gordon
Larry M
LM
Waring
Alan J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D001688:Biological Products; D019281:Dimerization; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008171:Lung Diseases / Q000188:drug therapy / Q000503:physiopathology; D008176:Lung Volume Measurements; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D037701:Pulmonary Surfactant-Associated Protein B / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D037721:Pulmonary Surfactant-Associated Protein C / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D037661:Pulmonary Surfactant-Associated Proteins / Q000172:deficiency*; D011663:Pulmonary Surfactants / Q000032:analysis / Q000737:chemistry* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D007507:Therapeutic Irrigation
D001688:Biological Products; D010446:Peptide Fragments; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C072197:beractant