SP-B and SP-C containing new synthetic surfactant for treatment of extremely immature lamb lung.
Although superiority of synthetic surfactant over animal-driven surfactant has been known, there is no synthetic surfactant commercially available at present. Many trials have been made to develop synthetic surfactant comparable in function to animal-driven surfactant. The efficacy of treatment with a new synthetic surfactant (CHF5633) containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, SP-B analog, and SP-C analog was evaluated using immature newborn lamb model and compared with animal lung tissue-based surfactant Survanta. Lambs were treated with a clinical dose of 200 mg/kg CHF5633, 100 mg/kg Survanta, or air after 15 min initial ventilation. All the lambs treated with air died of respiratory distress within 90 min of age. During a 5 h study period, Pco(2) was maintained at 55 mmHg with 24 cmH(2)O peak inspiratory pressure for both groups. The preterm newborn lamb lung functions were dramatically improved by CHF5633 treatment. Slight, but significant superiority of CHF5633 over Survanta was demonstrated in tidal volume at 20 min and dynamic lung compliance at 20 and 300 min. The ultrastructure of CHF5633 was large with uniquely aggregated lipid particles. Increased uptake of CHF5633 by alveolar monocytes for catabolism was demonstrated by microphotograph, which might be associated with the higher treatment dose of CHF5633. The higher catabolism of CHF5633 was also suggested by the similar amount of surfactant lipid in bronchoalveolar lavage fluid (BALF) between CHF5633 and Survanta groups, despite the 2-fold higher treatment dose of CHF5633. Under the present ventilation protocol, lung inflammation was minimal for both groups, evaluated by inflammatory cell numbers in BALF and expression of IL-1β, IL-6, IL-8, and TNFα mRNA in the lung tissue. In conclusion, the new synthetic surfactant CHF5633 was effective in treating extremely immature newborn lambs with surfactant deficiency during the 5 h study period.
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
Atsuyasu
A
Sato
Machiko
M
Ikegami
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004334:Drug Administration Schedule; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008170:Lung Compliance / Q000187:drug effects; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000627:therapeutic use*; D010713:Phosphatidylcholines / Q000138:chemical synthesis* / Q000627:therapeutic use*; D010715:Phosphatidylglycerols / Q000737:chemistry; D047928:Premature Birth / Q000188:drug therapy* / Q000276:immunology; D011510:Proteolipids / Q000737:chemistry; D037701:Pulmonary Surfactant-Associated Protein B / Q000138:chemical synthesis* / Q000627:therapeutic use*; D037721:Pulmonary Surfactant-Associated Protein C / Q000138:chemical synthesis* / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000138:chemical synthesis* / Q000627:therapeutic use*; D012121:Respiration, Artificial; D034561:Sheep, Domestic; D013990:Tidal Volume / Q000187:drug effects
C000592408:CHF5633; D016207:Cytokines; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011510:Proteolipids; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine