1710 Cystic Fibrosis and Pregnancy — Predictive Factors

Abstract

Pulmonary surfactant production, measured by the saturated phosphatidylcholine/sphingomyelin (SPC/S) r a t i o , is delayed i n male r a b b i t fetuses a t 26 t o 28 days' gestation (Nielsen and Torday, Ped Res 14:459, 1979). W e have observed t h a t the SPC/S r a t i o i n lung lavage (LL) of female fetuses is quantitatively rel a t e d t o the number of neighboring male fetuses, suggesting t h a t the sex difference i s hormone-dependent. Therefore, we administered DHT t o pregnant r a b b i t does d a i l y from the 12th pogtconcept i o n a l day. Doses of 251119, lOmg and lmg/day were used t o show a dose/response relationship. The fetuses were delivered on the 26th day. The f e t a l lungs were lavaged with 5 x 0.51111 aliquots of iced s a l i n e . Fetal sex was determined by inspection of the gonads. Phospholipids were extracted from LL, chromatographed and then , measured by spectrodensitometry. A l l DHT doses eliminated the sex difference i n the LL SPC/S r a t i o . Increasing doses of DHT corr e l a t e d s i g n i f i c a n t l y with lower mean SPC/S r a t i o s (p<.05). The DHT e f f e c t w a s apparently organ-specific since there w a s s i g n i f icant i n h i b i t i o n of f e t a l lung alkaline phosphatase a c t i v i t y with no detectable e f f e c t on f e t a l duodenal alkaline phosphatase act i v i t y . This i s t h e f i r s t evidence of a s t e r o i d hormone delaying pulmonary surfactant production. These findings suggest a hormo--nal b a s i s f o r the known male disadvantage i n the Respiratory Distress Syndrome of the newborn. P a r t i a l l y supported by a grant from the King Trust. Far more e f f o r t has been applied t o the measurement of minimum surface tension ( a min) i n lung surfactant films than t o the identification of s p e c i f i c surfactant components responsible f o r surface tension-area (a-A) hysteresis,or t o the possible physiologic consequences of p a r t i c u l a r hysteresis c h a r a c t e r i s t i c s . In t h i s work we show t h a t saturated phospholipids (primarily dipalmitoyl phosphatidylcholine,DPPC), not only a c t t o allow the generation of low a ,,,in as known previously, but a l s o confer on lung surfactant t h e p a r t i c u l a r a-A hysteresis c h a r a c t e r i s t i c of an abrupt surface tension r i s e over a small area increment a t the s t a r t of film expansion. This rapid r i s e i n o can be shown t o exi s t even i f a surface excess of surfactant i s present a t t h e interface during film compression, and r e s u l t s from the constrained surface re-entry properties of DPPC. This large, rapid surface tension increase should be of basic import f o r t h e recruitment of d i f f e r e n t sized alveoli during inspiration,and hence f o r the uniform expansion of the alveolar network. Consideration of a-A hyst e r e s i s c h a r a c t e r i s t i c s i n combination with the development of low o ,,,in allows a view of lung surfactant function i n vivo t h a t i s consistent with c l i n i c a l findings i n neo...