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PubMed2002

Effect of exogenous pulmonary surfactant preparations on the structure of pulmonary alveoli in newborn rats.

Treatment of pre-term newborns with exogenous surfactant preparation is a well established part of the therapy for respiratory distress syndrome of the newborns (RDS). Since the introduction of surfactant into clinical practice in 1980, hundreds of studies have been published describing beneficial effects of such treatment. There is only limited number of morphological publications reporting adverse effects of surfactant administration. The aim of the present study is to describe morphological changes in the lung after surfactant administration to healthy newborn rats. Two types of surfactant were used: Exosurf (Glaxo Wellcome, England) and Survanta (Abbott Laboratories, USA). Surfactant preparation were given intratracheally in single dose (bolus) (100 mg of lipids per kg b.w.). Animals from control group received 0.9% saline in equivalent volume. Lung specimens were taken 15, 20, 25 and 30 minutes after drug administration and evaluated by light and electron microscopy. There was no damage in lungs from the control group. Tissue specimens from the Exosurf group revealed severe pathological changes: foci of atelectasis, frank edema in the parenchyma, focal disruption of air-blood barrier, hemorrhages in many alveoli, surfactant particles in many alveolar capillaries, and strongly activated alveolar macrophages. In this group changes appeared as early as 15 min after surfactant administration and intensity of lung injury increased with time. Also, Survanta administration caused damage to the lung tissue. However, the changes were less intense and appeared later (20-25 minutes after Survanta treatment). In conclusion, the presented morphological findings proved that exogenous surfactant administration to healthy rat newborns caused lung damage. Comparing two different surfactant preparation, Exosurf and Survanta, it was shown that the former one produced stronger and faster damage to lung alveoli than the latter one.

Animals↗
PubMed1996

Postnatal treatment with retinoic acid increases the number of pulmonary alveoli in rats.

Dexamethasone, a glucocorticosteroid hormone, inhibits the formation of alveoli; retinoids and glucocorticosteroid hormones can be mutually antagonistic. These observations led us to test the hypothesis that the administration of retinoic acid to postnatal rats would prevent the low alveolar number and the low body mass-specific gas-exchange surface area (Sa) produced by treatment with dexamethasone. We used serial lung sections to distinguish alveoli from alveolar ducts and stereological procedures that allow quantitation of alveoli uninfluenced by their size, shape, or distribution. Treatment with retinoic acid prevented the low number of alveoli and the low body mass-specific Sa caused by treatment with dexamethasone. In otherwise untreated rats, retinoic acid caused a 50% increase in the number of alveoli, but without an increase in Sa, suggesting the action of a regulatory mechanism to prevent unneeded Sa. These findings provide the first experimental support for the possibility that, in individuals with too few alveoli for adequate gas exchange, treatment with a pharmacological agent may provide preventative or remedial therapy.

Animals↗