Pregnant rabbits received bethamethasone (0.05, 0.2, 0.4, or 0.5 mg.kg-1.day-1) or vehicle control for 2 days before delivery of fetuses at 27 days gestation to evaluate dose-related effects on surfactant pool sizes with and without ventilation, pressure-volume measurements, lung protein leaks, and precursor incorporation into lung saturated phosphatidylcholine (PC). Alveolar wash-saturated PC pool sizes in betamethasone-exposed fetuses were less than in controls (P less than 0.01). At higher doses, total lung saturated PC also decreased (P less than 0.01). Maximal lung volumes on pressure-volume loops were larger than controls only at the 0.4 mg.kg-1.day-1 dose (P less than 0.05). The larger maximal volumes, despite decreased saturated PC pools, indicated increased responsiveness of the steroid-treated lungs to the smaller saturated PC pool sizes. Vascular-to-alveolar iodinated albumin leak decreased with steroid treatment independently of dose (P less than 0.01). No consistent pattern of increased precursor incorporation into saturated PC by lung slices was seen. Our results indicate that, in preterm rabbits exposed to a range of maternal corticosteroid doses, the beneficial lung maturational effect of structural alterations with increased responses to endogenous saturated PC pools was maximal even at the lowest dose.

ABSTRACT. We studied the effect on surfactant metabolism of 8 h of mechanical ventilation at tidal volumes of 13 2 0.3 ml/kg and very high tidal volumes of 28 f 1.5 ml/kg, with and without added COz, in the presence of an atrial right to left shunt in 4-to 8-day-old lambs. Similarly aged, spontaneously breathing lambs were used as controls. Right to left atrial shunts were created by inflating a balloon in the right atrium after a Rashkind atrial septostomy, thus creating a stable, easily controlled atrial shunt. Radiolabeled surfactant phospholipid precursors were used to probe incorporation into and secretion of surfactant phosphatidylcholine, whereas intratracheally administered labeled natural surfactant was used to evaluate alveolar clearance. Protein leak from the vascular space to the lungs was measured using radioactive iodine-labeled albumins. At the end of the 8-h study period, tissue association of alveolar surfactant was significantly increased to 63% in the mechanically hyperventilated lambs as compared to 44% in those lambs mechanically ventilated but not hyperventilated (p < 0.05) and to 39% in the spontaneously breathing control animals (p < 0.05). No increased surfactant secretion or decreased compliance was detected with hyperventilation. However, the lambs had very large surfactant-saturated phosphatidylcholine pool sizes, and a large portion (50%) was already in the alveolar pool, even in the spontaneously breathing lambs. Precursor incorporation into saturated phosphatidylcholine was similar in all groups, and very low and comparable protein leaks were seen in the different groups of lambs. These experiments did not detect any adverse effects of 8 h of mechanical ventilation, large atrial shunts or mechanical hyperventilation on the surfactant system of newborn lambs. (Pediatr Res 25:83-88,1989) In neonates with persistent pulmonary hypertension, hyperventilation has been considered an essential part of the ventilatory support ( I ) . Suprasystemic pulmonary arterial pressures cause right to left shunts at the patent foramen ovale and ductus arteriosus levels which result in progressive hypoxemia. The goal of hyperventilation is to attain a critically low P a c o~ and alkaline pH which may promote reversal of the right to left shunt by decreasing pulmonary artery pressures to less than systemic levels (1). However, infants often become less responsive to the same

The role of the sensory neuropeptide calcitonin gene-related peptide (CGRP) was studied in preterm and term neonates with sepsis and shock. CGRP levels in blood were measured by RIA. The identity of immunoreactive CGRP (irCGRP) in adult and infant human blood was confirmed by reverse phase-HPLC. CGRP levels were analyzed in a total of 189 samples (95 from cord blood and 94 from neonates). The gestational ages ranged from 24 to 43 wk, and the birth weights ranged from 520 to 4445 g. Cord samples were collected immediately after delivery and infant blood samples were collected within 12 h of birth. Samples were coded, and the data were assigned to groups after determination of CGRP levels. There was a weight- and gestation-dependent increase in irCGRP in the newborn population. The direct correlation of circulating CGRP with ascending birth weight and gestation may have significance in the development of the fetus. Infants with and without certain complications were grouped in 500-g intervals. CGRP levels in cord blood were significantly elevated when certain stressful situations existed in the mother. These included culture-positive chorioamnionitis, placental abruption, and severe preeclampsia. There was a similar elevation in CGRP in patient blood in infants with culture-positive sepsis and/or shock with blood pressure <2 SD from the mean for corresponding gestation. CGRP levels did not differ between male and female infants and did not appear to be influenced by type of delivery (vaginal versus cesarean section). There was no significant difference in CGRP level between cord and patient blood in preterm neonates, but at term gestation cord blood levels were slightly higher than those in the patient blood. These results suggest that inflammation and hemodynamic imbalance (e.g. shock) are associated with increased in CGRP levels in the circulation in neonates. Future studies will focus on the biologic effects of elevated CGRP during neonatal complications and will examine the utility of CGRP measurement for diagnosis and treatment of disease in preterm infants.

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