W. Alan Hodson

Correlations of Mechanical Stability, Morphology, Pulmonary Surfactant, and Phospholipid Content in the Developing Lamb Lung*

Pressure-volume characteristics and surface tension measurements of the lamb of 120 to 130 days gestational age were typical of the mature lung in the upper lobes and the immature lung in the lower lobes. By term both upper and lower lobes had findings characteristic of the mature animal. Phospholipid concentration per milligram DNA and per cent saturated fatty acids on pulmonary phosphatidyl choline were relatively constant from 60 to 120 days gestational age; thereafter there was a significant increase in both measurements. These changes usually coincided with an increase in osmiophilic inclusion bodies in the large alveolar cell.A concentration of disaturated phosphatidyl choline per milligram DNA in excess of 0.170 mg per mg was associated with a minimal surface tension below 13 dynes per cm (p < 0.001). Newborn animal lungs contained over 3 times this critical concentration, whereas adult lungs contained 1.5 times this value. The excess disaturated phosphatidyl choline per milligram DNA may represent a reservoir of pulmonary surfactant.

Lung Development in the Fetal Primate Macaca Nemestrina. III. HMD

Summary: Delivery of M. nemestrina at 80% of normal gestation provides a population of neonates at high risk for hyaline membrane disease (HMD). The diagnosis of HMD was made by the presence of reticulogranular densities and air bronchograms on chest radiographs. Patchy atelectasis was seen in the lungs of animals assigned by clinical and radiographic criteria to the HMD group and not in the normal lungs of animals matched for gestational and postnatal age. Total phospholipid and phosphatidylcholine in whole lung, airway lavage fluid, and surface-active materials were lower in animals with HMD. Amniotic fluid L/S ratios were lower in the group that developed HMD. Pressure-volume measurements indicated decreased distensibility and unstable terminal air spaces in the HMD group. Alveolar-arterial oxygen pressure differences were greater in animals with HMD. There were no differences between HMD and normal groups in body weight, lung weight, percent dry lung weight, gestational age, and postnatal age at death. This primate species, subjected to premature delivery, is a suitable animal model of HMD in human neonates.Speculation: An animal model of hyaline membrane disease (HMD) in a primate species is of interest to investigators of developmentally related pulmonary disorders. More complete knowledge of abnormalities in pulmonary function in HMD will contribute to development of both preventive and therapeutic measures and affords the opportunity to determine risks and benefits of such treatments to the fetus and newborn.

Prognostic and etiologic factors in hypoglycemia.

The outcome and the developmental status of the survivors among 71 children who in their earlier years had laboratory evidence of hypoglycemia have been analyzed. For the purposes of this study, the children were assigned to three main groups: (1) neonatal symptomatic hypoglycemia (subdivided into infants of both diabetic and nondiabetic mothers); (2) postneonatal symptomatic hypoglycemia; (3) postneonatal asymptomatic hypoglycemia. The observations and interpretations are summarized.

Lung development in the fetal primate Macaca nemestrina. I. Growth and compositional changes.

Summary: This report relates lung growth and composition to body growth in 23 fetal and 2 newborn Macaca nemestrina (pigtail monkey) during the last third of gestation.There was a linear relationship (r = 0.883) between gestational age and crown-rump length over the age range studied, and length increased by 1.18 mm/day. The average increment in body weight was 5.1 g/day.Total lung weight increased in a manner similar to total body weight (wet lung weight = 1.91 ± 0.44% of total body weight). Lung weight increased by 109 mg/day until term. A correlation of 0.849 was observed between lung weight and gestational age. There was a linear increase in lung dry mass with increasing gestational age (9 mg/day, r = 0.701) and with increasing body weight (1.38 mg/g body weight, r = 0.691). The dry weight of fetal lung accounted for 10.8 ± 2.9% of total lung weight throughout the gestational period studied. Dry weight increased to 22–23% after birth.There was a decrease in protein and DNA per g wet weight of lung with advancing gestational age. Increases in total protein, DNA, and hemoglobin reflected the increasing size of the lung. Because gestational age is correlated with body size, body weight, and lung weight, total lung protein and total lung DNA should not provide any great advantage over total lung weight as a denominator for quantitative estimates of changing cell constituents with growth. Protein and DNA do not increase with gestational age when plotted per g dry lung. DNA per g dry lung tends to decrease with maturity, suggesting an increase in cell size.Speculation: Whereas fetal lung growth is linearly related to body growth over the last third of gestation, both lung and body size show wide variance at any given age. Constituents of lung increase in a manner which varies from general lung or body growth and are best compared when expressed in relation to a common denominator such as a unit of lung dry weight.

Lung Development in the Fetal Primate, Macaca nemestrina. II. Pressure-Volume and Phospholipid Changes

Summary: The biological and physiologic maturation of the lung in the primate Macaca nemestrina (pigtail monkey) from 107 days of gestation through term is the subject of this report. Total lung volume increased approximately 100% during the last 20% of gestation (Fig. 1). The increase from 30% to 85% of total lung volume at a deflation pressure of 10 cm H2O indicates a marked change in lung stability during the last 30–40 days of gestation (Fig. 2). Lung phospholipid per g dry weight of lung more than doubles during the last 20% of gestation (Fig. 3). This increase in phospholipid is due almost entirely to an increase in lecithin, and surface active material (SAM) lecithin accounts for the major part of this increase (Figs. 4 and 5). The increases in total lung and SAM lecithin parallel but precede the increase in lecithin in amniotic fluid (Fig. 6). As lung SAM increases the amniotic fluid lecithin to sphingomyelin ratio also increases (Fig. 7 and Table 1). Low ratios of lecithin to protein in SAM are found before 135 days of gestation. Subsequently, the amount of lecithin increases and, although protein also increases, the ratio increases 4-fold (Fig. 8). The amount of lung required to reduce surface tension of 1 cm2 to 12 dynes tended to decrease with advancing gestational age (Fig. 9 and Table 1). Parallel studies of airway generation demonstrate a similarity to the human fetal lung. Thus, the structural, compositional, and physiologic changes described in our studies strongly support the use of the fetal monkey for studies of developmentally related disorders of the human lung.Speculation: Biochemical and functional maturational changes in the fetal M. nemestrina indicate its suitability for studies of develop-mentally related pulmonary disorders of the human. Premature delivery by cesarean section between 130 and 140 days should provide a satisfactory homolog for hyaline membrane disease.

VERTICAL DISTRIBUTION OF INSPIRED VOLUME DURING LIQUID VENTILATION WITH PERFLUOROCHEMICAL (PFC) LIQUID. ▴ 312

VERTICAL DISTRIBUTION OF INSPIRED VOLUME DURING LIQUID VENTILATION WITH PERFLUOROCHEMICAL (PFC) LIQUID. ▴ 312

1017 TIME OF INITIATION OF CPAP IN HMD

The effects of the time of application of CPAP on the mortality and morbidity of HMD were examined in 36 infants in 3 weight groups (<1200, 1201-1800 and ≥1801 gms). Infants were randomly assigned by weight group to early (E) or late (L) CPAP by nasal prongs when PaO2≤50 mgHg while breathing in FIO2=0.4 or 0.7, respectively. Results are shown below:There were no differences in mortality, need for artificial ventilation, time spent in an FIO2>0.3 or >0.7 or in the incidence of air leak or chronic lung disease. Eleven of nineteen infants assigned to late CPAP never required an FIO2≥0.7 and did not receive CPAP. The present study suggests that the early application of CPAP offers no measurable advantage over the late application of CPAP in the treatment of mild HMD.

969 SLEEP STATE AND MATURATION OF CO2 SENSITIVITY IN THE PREMATURE PRIMATE

Sleep apnea and altered CO2 sensitivity have been implicated in the pathophysiology of SIDS. To investigate the hypothesis that sleep state and postnatal maturation influence minute ventilation and steady state CO2 sensitivity, 7 healthy premature M. nemestrina were studied serially in the first 3 weeks of life. VE/Kg in room air, 2,3,4, and 5% CO2 was measured via nasal wrongs and hot wire anemometer and arterial gases were sampled in 3 animals after a steady state was attained. Sleep state was assessed from EEG, EOG, EMG and respiratory pattern.Baseline VE/Kg and VT/Kg increased and f decreased in REM and NREM sleep with increasing postnatal age (p<.05), but there were no differences in VE/Kg between the 2 states at each age. VE/Kg increased following inhalation of CO2 in each state at each postnatal age, but there were no significant differences in CO2 sensitivity between NREM and REM sleep. In NREM sleep CO2 sensitivity increased progressively with increasing postnatal age (p<.025) whereas in REM sleep this maturational increase in slope was not observed (p>.4). The CO2 ventilatory response curve shifted to the left in both states with increasing age.These results suggest that there is a sleep state specific difference in postnatal maturation of CO2 sensitivity - a progressive increase in NREM sleep and no significant change in REM sleep. Failure of this normal maturational increase in NREM sleep may be important to the pathophysiology of SIDS.