Plasminogen activator activity in preterm infants with respiratory distress syndrome: relationship to the development of bronchopulmonary dysplasia.
Respiratory distress syndrome (RDS) is characterized by the presence of fibrin-rich exudates in the alveoli. Fibrin and its degradation products may play an important role in the pathogenesis of bronchopulmonary dysplasia (BPD). The purpose of this study was to test the hypothesis that preterm neonates with RDS have depressed alveolar fibrinolytic activity and that those with RDS progressing to BPD have an even greater impairment in alveolar fibrinolysis. Serial tracheal aspirate (TA) samples from intubated neonates--9 control and 46 with RDS--were analyzed for fibrinolytic activity. In neonates with RDS, 26 resolved, 18 progressed to BPD, and 2 died before 28 d. Plasminogen activator (PA) and its inhibitor (PAI) were identified in TA by reverse fibrin autography and immunoblotting. Net PA/plasmin activity in TA was significantly depressed on d 1 of life in patients with self-resolved RDS (median = 20.85 ng/mL, p < 0.05) and RDS progressing to BPD (median = 4.97 ng/mL, p < 0.001) compared with control patients (median = 87.1 ng/mL). In addition, neonates progressing to BPD had significantly lower PA/plasmin activity on day one of life compared with neonates with self-resolved RDS (p < 0.001). ELISA for specific PA and PAI were not significantly different. We speculate that depressed fibrinolytic activity may place preterm neonates at risk for RDS and that the degree of this depression may predict the progression to BPD. In infants < or = 30 wk of gestation at birth with RDS, a PA/plasmin activity < or = 10.0 ng/mL on the 1st d of life had a positive predictive value of 80% (12/15) and a negative predictive value of 82% (9/11) for the progression to BPD.
Singhal
K K
KK
Department of Pediatrics, SUNY at Stony Brook School of Medicine 11794-8111, USA.
Parton
L A
LA
D000595:Amino Acid Sequence; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism* / Q000503:physiopathology; D014132:Trachea / Q000378:metabolism*
D015849:Plasminogen Inactivators; D010960:Plasminogen Activators