The Role of Pulmonary Steroid 11-Reductase a Activity in Lung Maturation in the Fetal Rat

Abstract

The effect of PEEP on lung mechanics and on the work of breathing was studied in 8 preterm lambs delivered by cesarean section at 134 days gestation. Indwelling arterial, venous, and tracheal cannulae were placed before clamping the cord. Aeeisted mechanical ventilation was performed at a tidal volume of 15/ml/ Kg and a rate of 30-401min at F102 of 0.95. Measurements of intraesophageal and tracheal preaeurea, air flow, tidal volume. and functional residual capacity enabled calculation of dynamic compliance (CL), specific compliance (CS), inspiretory resistarce (RI), expiratory resistance (RE), and work of breathing at 0. 3, 6, and 10 cm Hz0 PEEP. Dynamic compliance and CS decreased by 0.11 mllcm H2OlKg and 0.0051 llcm H20 per cm Hz0 PEEP respective ly for PEEP above 3 cm H20. Functional residual capacity incl~aaed (pc0.005) by 1.6 ml/Kg per cm Hz0 PEEP. Inspiratory resistance increased significantly (~~0 . 0 5 ) only between 0 and 6 cm H20 P E P while RE increased (p<0.05) between 0 and all higher levels of PEEP (3, 6, and 10 cm H20). Ae compared to 0 cm Hz0 PEEP (11.9 * 2.5 SE x loh ergs/min). the work of inspiration per unit time decreased 17% at 3 cm Hz0 and increased 10% and 80% at 6 and 10 cm Hz0 PEEP respectively. These data suggest that it is mechanically easier to breathe at low levels of PEEP (3 cm H20) than without PEEP or at hi h levels of PEEP (10 Pulmonary alveolar proteinosis i s a d i f f u s e pulmonary disease o f obscure e t i o l o g y characterized by abnormal accumulations o f phospholipids i n the lung. Despite severe pulmonary d i s a b i l i t i e s there i s a s t r i k i n g absence o f i n f l a m t o r y c e l l s and f i b r o s i s i n the lungs o f these patients. W e have examined the lung washings and blood from f i v e patients w i t h t h i s disease i n an attempt t o discover whether there are any i n h i b i t o r s o f the normal i nf l a m t o r y responses l o c a l l y o r systemically. The complete peripheral blood counts and numbers o f T and B lymphocytes and monocytes were e n t i r e l y normal i n a l l patients. The c e l l u l a r components o f the lung washings were p r i m a r i l y mononuclear c e l l s which exhibited histochemical and surface characteristics t y p i c a l o f alveolar macrophages (AM). Morphologically, these AM were many times larger than AM from control patients and were f i l l e d w i t h amorphous material. The lung washings o f the patients i nh i b i t e d Con A and pokeweed mitogen stimulation o f allogenic peripheral blood lymphocytes by >go%, but had no s i g n i f i c a n t effects on PHA stimulation. Their sera i n h i b i t e d stimulation by a l l three mitogens >95%. This i n h i b i t i o n was not due t o cytot o x i c i t y . When the lung washings were injected into normal r a b b i t peritoneal cavities, there was no i n h i b i t i o n o f accumulation of e i t h e r PMNs o r peritoneal macrophages as stimulated by mineral o i l . I n addition, the lung washings stimulated RNA synthesis by r a b b i t AM. There i s gene...

Corticosterone Metabolism and the Incorporation of Leucine, Uridine, and Thymidine into Fetal Mouse Brain

“…Inhibition of this reaction by 11-ketoprogesterone was shown to inhibit lung maturation in fetal rats (12). In a similar manner, inhibition of the dehydrogenase reaction by 11-epicorticosterone enhanced the action of corticosterone as measured by glycogen deposition in neonatal mice (1).…”

Corticosteroids, Ornithine Decarboxylase Activity and the Incorporation of Leucine, Uridine, and Thymidine into Mouse Placenta

“…The latter is abundant in fetal tissues until late gestation, and reduction to the 116-OH configuration increases the amount of active hormone at the expense of the inactive metabolite. Inhibition of this reaction prevented maturation of fetal rat lunq, as measured by phospholipid synthesis (5). Rising reductase activity in fetal mouse liver (3) coincided with a decrease in the dehydrogenation reaction in mouse brain, which was considered responsible for a marked decrease in the rate of incorporation of leucine, uridine and thymidine into fetal mouse brain (7).…”

Human Fetal Lung Type II Pneumonocytes in Monolayer Cell Culture: The Influence of Oxidant Stress, Cortisol Environment, and Soluble Fibroblast Factors

“…The uptake of 3~-choline into DSPC was estimated according to the method of Mason et al (12) as described previously (20). Isotope counting was performed in a Searle Isocap 300 liquid scintillation spectrophotometer and the results are expressed as cpm/ lo3 cells.…”

“…The influence of differing oxygen tensions upon growth and incorporation of choline into saturated phosphatidylcholine (DSPC), a major functional component of the SAM in the neonatal lung (20), by isolated type I1 pneumonocytes grown in continuous monolayer cell culture have, therefore, been examined. The effect of pretreatment with cortisol before the oxidant stress has also been examined because this is a recognized form of therapy to enhance fetal lung maturation in premature fetuses likely to develop RDS ( I I).…”