Effects of a recombinant surfactant protein-C-based surfactant on lung function and the pulmonary surfactant system in a model of meconium aspiration syndrome.
OBJECTIVE
Meconium aspiration syndrome (MAS) remains a relevant cause of neonatal respiratory failure and is characterized by severe impairment of pulmonary gas exchange, surfactant inactivation, and pronounced inflammatory changes. Surfactant administration has been shown as an effective treatment strategy in MAS. The present study aimed at investigating the impact of a recombinant surfactant protein (SP)-C-based surfactant on pulmonary gas exchange and lung function in this model of neonatal lung injury. Furthermore, SP-B and -C were determined on the transcriptional and protein level.


METHODS
Laboratory experiment.


METHODS
University laboratory.


METHODS
Twenty three newborn piglets (median age 6 days, weight 1900-2500 g).


METHODS
Piglets were intubated and mechanically ventilated and then received 20% sterile meconium (5 mL/kg) for induction of lung injury. After 30 mins, animals were randomized for control (n = 7, MAS controls), recombinant SP-C surfactant (n = 8), or natural surfactant (n = 8). Surfactant preparations were administered as an intratracheal bolus (75 mg/kg), and animals were ventilated for another 330 mins. Nonventilated newborn piglets at term (n = 28; median weight 1484 g, range 720-1990 g) served as a healthy reference group (healthy controls).


RESULTS
Lung function variables, arterial blood gas samples, and lung tissues were obtained. Expression of SP-B and -C messenger RNA was quantified in left lung lobe tissue using real-time polymerase chain reaction. Protein concentrations were determined by enzyme-linked immunosorbent assay. Scanning electron microscopy and transmission electron microscopy were performed in tissue samples of the right lung lobe. Compared with healthy controls, SP-B messenger RNA expression was significantly increased in MAS (p < .02), whereas SP-C messenger RNA expression was found to be significantly reduced (p < .001). SP concentrations, however, were not significantly different. Although a significant improvement of gas exchange and lung function was observed after surfactant administration in both groups, surfactant messenger RNA expression and protein concentrations were not significantly altered. Scanning and transmission electron microscopy showed severe pulmonary ultrastructural changes after meconium aspiration improving after surfactant treatment.


CONCLUSIONS
Impairment of lung function in MAS, associated with marked changes in SP messenger RNA expression, can be sufficiently treated using recombinant SP-C-based or natural surfactant. Despite improved lung function and gas exchange as well as pulmonary ultrastructure after treatment, pulmonary SP messenger RNA expression and concentrations remained significantly affected, giving important insight into the time course following surfactant treatment in MAS.
Hilgendorff
Anne
A
Department of Pediatrics and Neonatology, Justus-Liebig-University Giessen, Germany.
Doerner
Martin
M
Rawer
Daniel
D
Leick
Jürgen
J
Trotter
Andreas
A
Ebsen
Michael
M
Ruppert
Clemens
C
Günther
Andreas
A
Gortner
Ludwig
L
Reiss
Irwin
I
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008470:Meconium; D008471:Meconium Aspiration Syndrome / Q000188:drug therapy*; D008969:Molecular Sequence Data; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D012129:Respiratory Function Tests; D012131:Respiratory Insufficiency / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013552:Swine
D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D011994:Recombinant Proteins