Uptake and degradation of Curosurf after tracheal administration to newborn and adult rabbits

Abstract

This paper examines the removal from the airways of Curosurf, a commercial surfactant derived from porcine lungs, administered at pharmacological concentrations to newborn or adult animals. Curosurf was labelled by the addition of radioactive dipalmitoyl phosphatidylcholine (DPPC) and administered intratracheally to newborn and adult rabbits at a dose of 200 mg x kg(-1) body weight. The disappearance of DPPC from the airways and its appearance in alveolar macrophages, lung parenchyma, lamellar bodies, serum, liver, kidneys and brain was then studied for 24-48 h. The in vitro degradation of Curosurf DPPC by alveolar macrophages was also studied. During the first 3 h after instillation, large amounts of Curosurf left the airways and became associated with tissue, indicating that it mixed rapidly with the endogenous pools of surfactant. A fraction of administered DPPC became associated with the lamellar bodies, suggesting that Curosurf can be recycled. Curosurf administration did not stop the secretion of endogenous surfactant. Very little intact radioactive DPPC could be recovered at any time in alveolar macrophages, however, macrophages have the ability, in vitro, to degrade Curosurf. Newborn rabbits lose Curosurf from the lungs at a slower rate than adult rabbits. One and two days after instillation, organic extracts from the liver, kidney, brain and serum contained small but measurable amounts of radioactivity. These results indicate that Curosurf rapidly enters the pathways of surfactant metabolism and that alveolar macrophages may play an important role in the catabolism of Curosurf.

Spontaneous Breathing or Mechanical Ventilation Alters Lung Compliance and Tissue Association of Exogenous Surfactant in Preterm Newborn Rabbits

“…cannot be recovered by BAL (14,(35)(36)(37)(38). We found the immediate tissue association of administered surfactant to be~25%, which is in agreement with previous reports.…”

“…Many authors have described the rapid tissue association of surfactant after intratracheal administration, but its functional significance remains unclear (14,(35)(36)(37)(38). To explain this phenomenon simply by inadequacy of the lavage technique is not sufficient in light of the results of this study, in which the same procedure produced different results in different treatment groups.…”

“…In the spontaneously breathing preterm or 3-d-old rabbit, the distribution of intratracheally administered, radiolabeled surfactant shows a dramatic change during the first 3 h, when a significant amount of label disappears from the airspaces and becomes tissue associated. After that, the amount of label recovered in the lavage reaches a fairly stable level, increasing only slowly over 24 h, presumably as a result of surfactant recycling (36,37). In the newborn animal, surfactant is recycled with Ͼ90% efficiency, but the time point when intratracheally administered surfactant reappears in the alveoli after recycling remains to be determined (41).…”

“…In the newborn animal, surfactant is recycled with Ͼ90% efficiency, but the time point when intratracheally administered surfactant reappears in the alveoli after recycling remains to be determined (41). Studies indicate that it takes several hours before the recovery of surfactant in alveolar washes is influenced by significant amounts of recycled material and that mechanical ventilation may hinder resecretion in preterm rabbits (36,37). Thus, the recovery of surfactant in alveolar washes after 4 h is not likely to be significantly influenced by recycled material.…”

Surfactant protein B and A concentrations are increased in neonatal pneumonia

“…Finally, to measure DSPC kinetics, we used (U-13 C-PA)dipalmitoylphosphatidylcholine as tracer, in agreement with previous animal studies (29) but without the possibility to prove the actual mixing with the endogenous surfactant pool.…”