Intrauterine hypercarbia and lamb lung surfactant synthesis.

Prenatal asphyxia resulting in hypoxia, hypercarbia and amniotic fluid aspiration reduces the synthesis of the pulmonary surfactant. Using 135-day fetal lambs we studied the in utero effects of hypercarbic acidosis alone on fetal breathing activity, excised lung pressure-volume relationships and lamellar body (LB) surfactant disaturated phosphatidylcholine (DSPC) pool size and specific activity for [14C]palmitate. Fetal PaCO2 levels greater than 125 mm Hg for 30 min were associated with pH values less than 7.0 and very vigorous breathing activity. Analysis 22 h after the period of hypercarbic acidosis demonstrated no differences in pressure-volume relationships or the quantity of lamellar body surfactant DSPC. The specific activity of lamellar body DSPC also was not different although total label (dpm) per gram dry weight was higher and label was detected in the lavage fluid earlier in the acidotic lambs than controls. We conclude from these data that hypercarbic acidosis does not influence the synthesis or function of the pulmonary surfactant as assessed in this system. From these results and prior work from our laboratory we can infer that hypoxia remains the most probable cause for reduced surfactant synthesis in the asphyxiated fetus.

Activities of the initial enzymes of glycerolipid and sphingolipid synthesis in lung microsomes from rats exposed to air or 85% oxygen.

Lungs of adult rats exposed to 85% oxygen undergo extensive cellular reorganization; therefore, to investigate changes in lipid metabolism the initial enzymes of glycerolipid and sphingolipid synthesis were measured in lung microsomes. After 1 week of O2 treatment, the specific activity of the glycerol 3-phosphate acyltransferase increased to nearly twice that of the controls and remained elevated for the 3 weeks of study. Serine palmitoyl-transferase activities were approximately the same for both groups. These results suggest that in addition to cellular proliferation caused by hyperoxia there are also selective changes in glycerolipid synthesis, which may explain the decreased sphingomyelin content of lung and lamellar bodies.

Rat lung surfactant kinetics biochemical and morphometric correlation.

Biochemical and morphometric techniques were combined to estimate the distribution and flux or rat lung disaturated phosphatidylcholine (DSPC) in surfactant pathways. We found 126 +/- 8 X 10(6) alveolar epithelial type II (AEP II) cells per lung, each containing 150 +/- 30 lamellar bodies (LB). High yields of LB were isolated by centrifugation of lung homogenates with a discontinuous sucrose density gradient. Measurement of DSPC in LB and alveolar lavage (LV) material demonstrated that only 30% (LB 14%, LV 16%) of lung DSPC was present in these surfactant compartments. Radiolabeling of lung DSPC with [14C]palmitate demonstrated a product-precursor-relationship between LB and LV and a surfactant-associated DSPC flux of 90 microgram-lung-1 X h-1. We conclude that, although only 16% of lung DSPC is in an intracellular surfactant pathway at any time, all this DSPC is ultimately secreted onto the alveolar surface.

Lung phosphatidylcholine transfer in six vertebrate species. Correlations with surfactant parameters.

We have examined phosphatidylcholine transfer activity in lung-soluble fractions from six vertebrate species. There is a significant correlation between the amount of phosphatidylcholine transfer activity and both the alveolar surface area and surface active material. This suggested that phosphatidylcholine exchange proteins have a role in the lung surfactant system.

Fetal lamb lung phosphatidylcholine: response to asphyxia and recovery.

Acute fetal asphyxia resulting from maternal blood loss and hypotension causes a reduction in the incorporation of precursors into disaturated phosphatidylcholine, the principal lipid in the pulmonary surfactant. Treatment of the maternal hypotension is associated with return of fetal lung DSPC synthesis to control levels by 72 hours.

Radiological observations during transpyloric tube feeding in infants of low birth weight. Perforation of the duodenum and variations in normal duodenal anatomy.

Perforation of the duodenum is a serious complication of transpyloric tube feeding in infants of low birth weight. Polyvinyl chloride and (less commonly) silicone tubes have been implicated. Altered radiographic configuration of the tube in the region of the superior or inferior flexure, associated with clinical deterioration, pneumoperitoneum, peritonitis, or a retroperitoneal fistula, is diagnostic of duodenal perforation. The configuration of the tube may vary during uncomplicated transpyloric alimentation and is frequently incompatible with the expected anatomical course. Contrast examination may demonstrate normal anatomy or mobility of the distal duodenal loop as an adaptation to rigidity of the tube. The possibility of perforation appears to be increased at or adjacent to the flexures.

Fetal lamb lung lavage and its effect on lung phosphatidylcholine.

UNLABELLED: The lungs of intrauterine 135--136-day-old lambs were lavaged with amnionic fluid, with or without meconium, to determine the effect on lung phosphatidylcholine (PC) concentration, synthesis, and function. No differences were apparent between animals lavaged with amnionic fluid or amnionic fluid with meconium. When lavaged lungs were compared to nonlavaged controls, no detectable differences were observed in histology or the quantity of saturated (SPC) and unsaturated phosphatidylcholine (UPC). However, the lavaged lungs retained a larger fraction of maximal lung volume at 5 cm H2O distending pressure and the incorporation of (32P) orthophosphate into lung PC was significantly reduced. In addition, two lavaged animals who became acidotic (pH less than 7.20) exhibited decreased incorporation of 14C) palmitate into whole lung unsaturated, and saturated phosphatidylcholine. SPECULATION: These data indicate that amnionic fluid can reduce lamb lung de novo synthesis of PC and may contribute to the alterations in lung PC found in neonatal syndromes of respiratory distress. Acidosis may accentuate this effect.

Disaturated phosphatidylcholine in rat lungs with altered numbers of type II alveolar epithelial cells.

Rats exposed to 85 per cent oxygen for 9 days demonstrated an increase in lung deoxyribonucleic acid (DNA) specific acitvity for [3H]-thymidine and a significant increase in the volume of interstitial and alveolar epithelial cells. This included a 63 per cent increase in the number of Type II alveolar epithelial cells. Lamellar body volume per lung significantly increased in animals exposed to oxygen and was related to the increased number of Type II cells, because lamellar body volume expressed per Type II cell remained relatively constant and was comparable to control values. The concentration of whole lung disaturated phosphatidylcholine also increased significantly, but the concentration of unsaturated phosphatidylcholine did not increase. Concomitantly, there was a significant decrease in [32P]-orthophosphate and [14C]-palmitate disaturated phosphatidylcholine specific activity that was proportional to the increased number of alveolar epithelial Type II cells present.

Amniotic fluid cortisol in normal and diabetic pregnant women and its relation to respiratory disease in the neonate.

One hundred and thirty samples of amniotic fluid from normal and diabetic pregnant women were analyzed for cortisol concentration. In normal pregnancies, cortisol was present in low concentrations until 35 weeks' gestation, followed by a sharp rise at 36 weeks and a continued upward trend to 39 weeks. The rise after 35 weeks was delayed or absent in many patients with diabetes. In the combined population, the incidence of respiratory disease with a lecithin/sphingomyelin ratio greater than or equal to 2 was 26 per cent if the amniotic fluid cortisol was less than 4.3 microgram per 100 ml. and 2.9 per cent if the cortisol concentration was greater than or equal to 4.3 microgram per 100 ml.

Neonatal pneumonia associated with medium-chain triglyceride feeding supplement.

The appearance of a similar pattern of multifocal pulmonary consolidation in four neonates receiving undiluted medium-chain triglyceride oil suggested a cause-and-effect relationship. This was supported by the demonstration in rabbits that the transtracheal injection of MCTO caused severe pneumonia. It is suggested that MCTO be mixed with formula before it is given to neonates.

Lysophospholipase--transacylase from rat lung: isolation and partial purification.

Incubation of rat lung supernatant with 1-[1(-14)C] palmitoyl-sn-glycero-3-phosphocholine in the absence of any cofactors resulted in the release of radioactive fatty acid and the formation of phosphatidylcholine. The production of fatty acids (lysophospholipase activity) exceeded phosphatidylcholine formation (transacylase activity) about thereefold, although the relative extent of phosphatidylcholine formation was considerably greater than previously reported by Abe et al. (Biochim. Biophys. Acta, 369: 361-370, 1974). In agreement with these authors, evidence is presented suggesting that a single enzyme is responsible for both catalytic activities. The enzyme, provisionally denoted lysophospholipase-transacylase, was found primarily in the soluble fraction of rat lung and was purified approximately 250-fold. The enzyme had an estimated mol wt of 50,000. The ratio of lysophospholipase to transacylase activity in the purified enzyme could be varied depending upon the concentration and character of the lysophosphatidylcholine and the ration of substrate to products. The degree of esterification of 1-acyl lysophosphatidylcholine was altered with mixtures of different molecular species of substrate, indicating acyl chain selectivity in the transfer process. This enzyme was capable of synthesizing disaturated phosphatidylcholine, an important component of the pulmonary surfactant. Three lysophospholipases purified from other sources did not possess this transacylase activity.

Whole and disaturated lung phosphatidylcholine in cortisol-treated, intrauterine growth-retarded and twin control lambs at different gestational ages.

Lambs 116--124 days gestation infused in utero for 75 h with cortisol showed, when compared to twin controls, more mature lung histology and pressure-volume relationships. 32P orthophosphate incorporation into whole lung phosphatidylcholine (PC) was increased in the four cortisol-treated lambs at 116--117 days but not at 121, 123, and 124 days gestation. 14C palmitate incorporation into PC or disaturated phosphatidylcholine (DSPC) was not enhanced at 116--117 days gestation. At 121 days in a cortisol-treated and at 128 days in a growth-retarded lamb fetus not treated with cortisol, a larger quantity of DSPC was present although the incorporation of 14C palmitate into DSPC per milligram DNA was the same. This indicated that the synthesis of DSPC had been initiated in the cortisol-treated and growth-retarded animals prior to the controls and at the time of sacrifice both were incorporating 14C palmitate at a similar rate suggesting similar rates of synthesis.