Surfactant composition and function in a primate model of infant chronic lung disease: effects of inhaled nitric oxide.
Bronchopulmonary dysplasia, or chronic lung disease (CLD), of premature infants involves injury from hyperoxia and mechanical ventilation to an immature lung. We examined surfactant and nitric oxide (NO), which are developmentally deficient in premature infants, in the baboon model of developing CLD. Fetuses were delivered at 125 d gestation and were managed for 14 d with ventilation and oxygen prn without (controls) or with inhaled NO at 5 ppm. Compared with term infants, premature control infants had reduced maximal lung volume, decreased tissue content of surfactant proteins SP-A, -B, and -C, abnormal lavage surfactant as assessed by pulsating bubble surfactometer, and a low concentration of SP-B/phospholipid. NO treatment significantly increased maximal lung volume and tissue SP-A and SP-C, reduced recovery of lavage surfactant by 33%, decreased the total protein:phospholipid ratio of surfactant by 50%, and had no effect on phospholipid composition or SP content except for SP-C (50%). In both treatment groups, levels of SP-B and SP-C in surfactant were negatively correlated with STmin, with a 5-fold greater SP efficiency for NO versus control animals. By contrast, lung volume and compliance were not correlated with surfactant function. We conclude that surfactant is often dysfunctional in developing CLD secondary to SP-B deficiency. NO treatment improves the apparent ability of hydrophobic SP to promote low surface tension, perhaps secondary to less protein inactivation of surfactant, and improves lung volume by a process unrelated to surfactant function.
Ballard
Philip L
PL
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 19104, USA. ballardp@email.chop.edu
Gonzales
Linda W
LW
Godinez
Rodolfo I
RI
Godinez
Marye H
MH
Savani
Rashmin C
RC
McCurnin
Donald C
DC
Gibson
Linda L
LL
Yoder
Bradley A
BA
Kerecman
Jay D
JD
Grubb
Peter H
PH
Shaul
Philip W
PW
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D048531:Papio papio; D047928:Premature Birth; D037661:Pulmonary Surfactant-Associated Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D009569:Nitric Oxide