A protein that interfered with surfactant function was isolated from the alveolar washes of prematurely delivered and ventilated lambs. This inhibitor was recovered following sequential precipitation with polyethylene glycol, Affi-Gel Blue, and diethylaminoethyl (DEAE) cellulose chromatography as a protein of approximately 110,000 mol wt. Compared to surfactant alone or surfactant and bovine serum albumin, the purified inhibitor increased the time required for surfactant to spread, increased both maximal and minimal surface tensions, increased the percent surface area that had to be compressed to reach a minimum surface tension of less than 15 dyn/cm, and delayed the surface adsorption of surfactant. The effect of inhibitor on the minimum surface tensions of surfactant solutions was inversely related to surfactant concentration. A radioimmunoassay was used to estimate that approximately 10% of the protein from plasma of premature lambs and alveolar washes after 4 h of ventilation was inhibitory. Following the simultaneous intravascular injection of labeled inhibitor and bovine serum albumin, about 4% of the radioactivity associated with both proteins was recovered in alveolar washes and 6% was associated with lung tissue after alveolar wash. This large proportionate leakage of both proteins did not occur in other tissues. The inhibitor affected multiple measurements of surfactant function in vitro and its presence may contribute to a surfactant deficiency state in the immature lung.
A marked increase in sympathoadrenal activity at birth has been described in animals and humans. Studies to determine whether the magnitude and duration of the catecholamine surge at birth in preterm lambs is similar to full-term lambs were undertaken using an acutely exteriorized fetal lamb. To maintain a physiologically stable preparation, all preterm lambs were given natural sheep surfactant intratracheally before the first breath. Base-line catecholamine values were similar in the full-term and preterm lambs. After umbilical cord cutting there was a marked increase in circulating norepinephrine (NE) and epinephrine (E) in both full-term and preterm animals. The preterm animals exhibited a delayed but exaggerated elevation of both NE and E relative to term animals. The peak preterm value for NE (3.8 +/- 1.2 ng/ml) occurred at 60 min and exceeded the peak NE value 1.2 ng/ml observed at 15 min in full-term animals. The peak E concentration in preterm animals was over 9 ng/ml between 2 and 3 h of age, whereas full-term animals reached a peak value of 1.1 ng/ml at 5 min. Heart rate and blood pressure rose abruptly to peak values by 5-15 min in full-term animals. Changes in heart rate and mean arterial pressure were less profound and more gradual in preterm animals. Full-term animals also demonstrated a five-to sevenfold increase in plasma free fatty acids, whereas concentrations in preterm animals increased only two- to threefold. There was a similarly blunted response in blood glucose in preterm animals. The catecholamine surge at birth may be an important adaptive phenomenon with physiological implications.
The distribution and ontogeny of tissue prolyl endopeptidase and pyroglutamyl peptidase I activities were studied in the rat from the 7th day before birth to adulthood. While low levels of prolyl endopeptidase activity were demonstrable in many fetal tissues, activity in brain cortex, hypothalamus, lung, and kidney increased dramatically during the 2 wk after birth, gradually returning to adult levels. In adult rats, levels of tissue prolyl endopeptidase activity were highest in kidney, when compared with the intermediate levels in brain cortex, hypothalamus, and liver. Pyroglutamyl peptidase activity was widely distributed in adult rat tissues with high levels in kidney and liver that exceeded intermediate levels in brain cortex and hypothalamus. Pyroglutamyl peptidase activities in fetal gut, brain, and lung tissue were elevated above adult values. In contrast to the development changes in prolyl endopeptidase activities, pyroglutamyl peptidase activity remained elevated above adult levels only during the first week of life. These results indicate that both prolyl endopeptidase and pyroglutamyl peptidase activities in the rat are developmentally regulated.
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