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Previous studies in subhuman primates have encompassed the entire third trimester to profile general patterns of fetal lung development(FLD); however, this work has not expanded the data base at key gestational ages(GA) to elucidate precise developmental changes. Accordingly, we have performed comprehensive pulmonary physiologic and biochemical analyses in 17 nonbreathing rhesus fetuses delivered by C-section at 4 gestational ages(term=165 days). Lung data including phosphatidylcholine(PC) and phosphatidylglycerol(PG) are presented in the table below(per gram wet wt) as mean±S.E. values. Marked changes in phospholipids were noted at 155 days GA. Additionally, lung protein, wet weight, %V10 and selected fatty acids in PC increased with advancing GA. Although parallel increases occurred in lung PC, DSPC and PG, mature physiologic indices were obtained later in gestation. Furthermore, amniotic fluid analyses revealed no clear relationship between PG concentration and lung maturation.

Fetal breathing movements (FBM) stimulate fetal lung growth. Since lung distension has been associated with fetal lung growth, we postulated that FBM transiently increase the total volume of fluid (TVF) in the potential airways and air spaces. In 6 chronically catheterized fetal sheep (121–137 days) we cannulated the trachea with 2 small, catheters (6F balloon-tipped, 6F end-hole); the trachea remained patent. FBM (by tracheal catheter) were recorded continuously after-surgery. On alternate days after ≥9 minutes of either FBM or no FBM we inflated the balloon-tipped catheter to occlude the trachea. Then we aspirated fluid from the lungs until ≤0.4 ml/min was obtained. In 3 fetuses we measured by inulin dilution the TVF in the lungs to determine the completeness of the aspiration. The TVF after FBM were 49.0 and 51.5 ml/kg; TVF after no FBM was 43.6 ml/kg. The volume that remained after aspiration was 19.6±0.9 ml/kg (mean±SD). The daily incidence of FBM was similar on both study days for each fetus. In every fetus, the volume aspirated after FBM (69.9±18.1 ml) was greater than that after no FBM (40.8±21.4 ml)(p 0.01). We conclude that in the fetus with a patent trachea, FBM increase the volume of fluid that can be aspirated from the lungs. This suggests that the TVF in the airways and air spaces may also increase and may stimulate lung growth. (USPHS HL-27366 and IRG UTHSCSA)

The role of TRH on ovine fetal L maturation was studied in 12 euthyroid fetuses (F). Beginning at 127 days, 6 F received 3 daily bolus IV injections (I) of 50 ug TRH and 6 control F received saline (S). All were sacrificed at 130 days. The mean body weight and weight of selected organs were similar. Initially, the mean serum thyroxine ([T4]), triiodothyronine ([T3]) and reverse T3 ([rT3]) levels were similar in both groups. In the S group, mean serum iodothyronine levels were similar throughout the study period. In the TRH group, mean (± SEM) [T4] significantly increased from 12.4 ± 2.0 ug/dl to 20.9 ±2.9 ug/.dl (p

1838 METYRAPONE DELAYS MATURATION OF FETAL LUNG SURFACTANT ANTIOXIDANT ENZYMES: ARE BOTH UNDER ENDOGENOUS GLUCOCORTICOID CONTROL?

Fetal lung explants develop the capacity to actively synthesize saturated phosphatidylcholine (SPC) in the presence of culture medium fortified with serum. The following criteria were set up to test whether this process is glucocorticoid(GC)-dependent: 1) GC must promote active SPC synthesis; 2) antiGC must inhibit active SPC synthesis; 3) in the absence of GC active SPC synthesis will not occur, but activity can be restored by adding GC. Day 19 fetal rabbit lung explants were cultured under the following conditions: Waymouth's medium and 10% fetal calf serum(FCS) or 10% stripped FCS(FCS-) plus cortisol(GC) or cortexolone (antiGC) for 9 days. SPC synthesis was quantified by measuring the rate of 3H-choline incorporated into 3H-SPC. Therefore 1)both serumGC(a) and cortisol (b) support active SPC synthesis; 2)serum GC is inhibited by antiGC(c);3)in the absence of GC(d) active SPC synthesis does not occur, but can be stimulated by cortisol(e). Therefore the fetal lung is dependent on GC for development of active SPC production. This study supported by NIH Grant #HL28315.

As an ongoing project,Reviews in Perinatal Medicinewill be welcomed by many who would rather read reviews than current literature. Dr Emile M. Scarpelli, Director of the Pediatric Pulmonary Center, Albert Einstein College of Medicine, New York, is a veteran editor who has authored and edited several books. His co-editor is Dr Ermelando V. Cosmi, an anesthesiologist at the University of Rome. Both of the editors have done and are doing research on fetuses, including Dr Scarpelli's research on developing fetal lung. The editors have attracted many distinguished participants among their international cast both in their editorial board and in their contributors (many members of the editorial board also are contributors) who cover a number of timely topics in perinatal medicine. For the introductory volume they scarcely could have found two more interesting or informative persons than Drs Lawrence Longo (with Gordon Power) and Abraham Rudolph to author the

Absorption of fetal lung liquid before and soon after birth is essential for the normal transition from placental to pulmonary gas exchange. We recently found that granular epithelial cells from lungs of adult and newborn rabbits actively extrude Na+ in exchange for K+; this process, which may be important in regulating lung fluid balance, was considerably slower in cells derived from fetal lungs. To test the hypothesis that either air-breathing or labor, or both, might activate this process, we harvested granular pneumonocytes from lungs of fetal and newborn rabbits and measured 86Rb+ (K+) uptake by these cells in the presence or absence of 10−4 M ouabain (o), which inhibits Na+-K+-ATPase. Fetal rabbits, preterm (28 d) and term (31 d), experienced neither labor nor air-breathing. Newborn rabbits, born by cesarean section (cs) or vaginally (v), breathed for up to 2 h after birth. Pups born operatively did not experience labor. Results (±s)

Following planned termination of pregnancy, infants of diabetic mothers (IDM) have shown a continued vulnerability to the respiratory-distress syndrome (RDS) suggesting false-positive fetal lung maturity testing. Adequacy of the lecithin/sphingomyelin (L/S) ratio for predicting RDS was studied in 56 diabetic (DM) and 50 nondiabetic (ND) pregnancies. Amniotic-fluid samples (n=130) were assayed for 1- and 2-dimensional (dim) thinlayer chromatographic (TLC) L/S ratios, and phosphatidylglycerol (PG) and phosphatidylinositol (PI) assays. L/S ratios for all pregnancies by both TLC techniques revealed higher 1-dim values from 36-38 wk gestation (P 38 wk with L/S ratios > 3. PG detection by class of DM was delayed for class A pregnancies beyond 36.5 wk (r=0.6551, P

Published reports suggest that drainage of fetal lung liquid begins immediately at birth, usually is complete in 4-6 h, but is delayed by cesarean section (CS). To re-examine this process, we measured pulmonary blood volume (PBV), extravascular lung water (EVLW), and size of perivascular fluid cuffs in frozen lung sections of 152 full-term rabbits born vaginally or by CS. We killed the rabbits before they breathed or at varying intervals, up to 24 h, postnatally by immersion in liquid N2 after intraperitoneal barbiturate. Ten additional rabbits, killed before breathing, had CS after labor. CS rabbits (n=83) weighed 50 ± 7 g, vaginally-born (n=69) weighed 51 ± 8 g. Results: (1) a comparable increase in PBV after breathing in both groups; (2) EVLW significantly less (by 17%) in fetuses born vaginally, compared to those born by CS without labor, but no difference in EVLW for fetuses born either vaginally or by CS after labor; (3) no postnatal decrease in EVLW until 30-60 min of age irrespective of type of delivery; thereafter, decrease in EVLW over 24 h was similar for the 2 groups; (4) maximal perivascular cuffing at 30 min of age, virtually absent by 2-4 h after birth for both groups. Our results suggest that lung liquid content of fetal rabbits decreases during labor, but does not diminish further until 30-60 min after birth; a compliant perivascular tissue space accomodates excess fetal lung liquid until its later removal; and type of delivery has no effect on the pattern of postnatal lung liquid drainage.

The effect of prenatally administered Indomethacin (Indo), a prostaglandin synthetase inhibitor, on alveolar disaturated phosphotidylcholine (DSPC) in the fetal and neonatal rabbit was studied. Pregnant rabbits were injected S.C. with either 0.01 M Na2CO3 or 3 mg/kg Indo in 0.01 M Na2CO3 b.i.d. from 27 through 29 days of gestation inclusive (3 day group). Fetuses were sacrificed on day 30 and the lungs washed with 0.9% NaCl. Newborn pups were delivered and allowed to breathe air for either 0.5 or 1.0 hours and then lung washes obtained. Pregnant does were also given Indo (3 mg/kg b.i.d.) or Na2CO3 on day 29 and fetal lung washes obtained on day 30 (1 day group). Results: Thus during fetal life alveolar DSPC was halved by Indo by 24 hrs but doubled by 3 d. In the pups given 3 d of Indo prior to delivery alveolar DSPC was increased by 54% at 0.5 hrs air breathing but there was no effect by 1 hr. We postulate that Indo temporarily decreases fetal lung surfactant release but that fetal breathing activity is more important in determining release than prostaglandins. Furthermore, Indo does not inhibit the massive release associated with the onset of air breathing.

STIMULATION OF FETAL LUNG PHOSPHATIDYLCHOL INE SYNTHESIS BY CONDITIONED MEDIUM FROM FETAL LUNG EXPLANTS

The alveolar epithelium (AE) of fetal lungs actively transports Cl− into the alveolar lumen, resulting in a high concentration of Cl− in fetal lung fluid. REcently, we found that in the aqueous subphase (AS) of mature alveoli the Cl− concentration is equal to that in serum, consistent with little or no active transport of Cl− by the resting AE. If a Cl− pump exists in mature AE, then drugs that stimulate or decrease active Cl− transport in other tissues might alter the concentration of Cl− in the AS. To test this hypothesis, we measured the concentration of Cl− in the AS of anesthetized rabbits before and after intravenous terbutaline (0.3 mg/kg), a drug that stimulates active Cl− transport in other types of respiratory epithelia. The measurements were made by puncturing alveoli visible through the pleura with a Cl− selective microelectrode. Baseline Cl− = 98 ± 5 meq/L (mean ± SD, n = 5). The Cl− increased to 116 ± 4 (n = 5) within 30 to 40 min after the terbutaline, a significant change (p

233 INTERACTION OF GLUCOCORTICOID, THYROID HORMONE AND PROLACTIN IN STIMULATION OF PHOSPHATIDYLCHOLINE (PC) SYNTHESIS IN CULTURED FETAL LUNG

For a number of years we have been struck by the absence of truly pathologic lesions as a cause of death among many of the immature infants born in the Pennsylvania Hospital. Many of these infants appeared to have died of respiratory failure, as evidenced by cyanosis and gasping respirations in the presence of seemingly normal cardiac function. In fact, it was usual for the heart to continue beating even after respirations had ceased. Numerous embryologic studies on the development of the fetal lung and the lining of the alveoli have been made; yet in the literature there has been little discussion of the clinical significance of the results of such studies. Although death in the premature infant is undoubtedly caused by a complex mechanism which includes anatomic and metabolic dysfunction of numerous organs, it seemed desirable to make an anatomic study of the fetal lung to determine what bearing

The first edition of Dr. Avery9s monograph, published in 1964, was rapidly accepted as an extraordinarily useful and definitive summary of the available information on development of the fetal lung and the function of the respiratory system in the perinatal period. It served also as an excellent review of the important respiratory conditions affecting newborn infants as well as a useful guide to treat these conditions. Some may not believe that such a comprehensive work would require revision in only 4 years, but it is obvious from reading this new edition that a great deal has been learned during the last few years about this rapidly expanding field.

This book contains eight reviews written by outstanding authorities on different aspects of the placenta and fetal membranes, a report of a conference held in Princeton, N. J., devoted to a full discussion of current placenta research, a survey of the literature, a bibliography of more than 2,700 references, and a list of investigations of current research being conducted in the United States and abroad. The book is dedicated to George L. Streeter and George B. Wislocki. The eight reviews and the contributors are as follows: (1) Comparative Aspects of the Hormonal Function, by E. C. Amoroso, (2) Histophysical Considerations, by E. W. Dempsey, (3) The Placental Circulation, by E. M. Ramsey, (4) The Placenta as the Fetal Lung, by D. H. Barron, (5) Transmission of Antibodies from Mother to Fetus, by F. W. R. Brambell and W. A. Hemmings, (6) Placental Function and Fetal Nutrition, by J. Dancis, (7)