Protein- and lipid modification of natural bovine surfactant. Effects in experimental lung failure with special consideration of the response in neonates.
Surfactant therapy does not lead to a uniform, optimal and sustained effect on gas exchange in neonatal respiratory distress syndrome (RDS) and acute respiratory distress syndrome (ARDS). The aim of the present study therefore was to compare the effects of a lipid-enriched and protein-modified natural surfactant preparations with a licensed, clinically used bovine surfactant preparation - SF-Ril (Alveofact).


METHODS
SF-Ril was enriched with phosphatidylglycerol, sphingomyeline, phosphatidylethanolamine plasmalogen, phosphatidylethanolamine. Furthermore, SF-Ril was modified with increased surfactant protein B (SP-B)/surfactant protein C (SP-C) content and finally a mercaptoethanol (ME) treated preparation for breaking the sulfhydril bondage of SP-B/SP-C by chemical reduction in methylene chloride using ME was developed. Finally ME was removed by vacuum extraction. These modified surfactants were tested at a dosage of 100 mg/ kg each in a model of respiratory failure induced by lung lavage in male adult rats and compared with SF-Ril at an identical dosage. Mechanical ventilation was standardised with fraction of inspiratory oxygen (FiO2) 1.0 and time-cycled pressure limited ventilation 16/0.8 cmH2O before and 26/6 cmH2O (peak inspiratory pressure/positive endexpiratory pressure) after lung lavage (target arterial oxygen pressure [pa02] < 100 mmHg), respiratory rate 36/min, inspiration/expiration time ratio 1:2.


RESULTS
During the observation period of 120 min, the sphingomyeline substituted and protein-modified (ME reduced) surfactant preparations exerted improved and sustained oxygenation compared with SF-Ril. Similar effects were observed for tidal volumes. All other preparations were equal or inferior to SF-Ril in our model.


CONCLUSIONS
For the development of surfactant preparations less prone for inactivation the above mentioned data may provide useful information, provided they can be confirmed in further investigations employing other alternative models.
Department of Pediatrics and Neonatology, University of the Saarland, Homburg/Saar Germany. kilgor@uniklinikum-saarland.de
Ludwig
L
Gortner
Wiebke
W
Maroske
Irwin
I
Reiss
Eberhard
E
Weller
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects*; D008171:Lung Diseases / Q000188:drug therapy* / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D011506:Proteins / Q000378:metabolism*; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D012121:Respiration, Artificial; D007507:Therapeutic Irrigation; D013990:Tidal Volume
D011506:Proteins; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D002245:Carbon Dioxide; D010100:Oxygen