Clearance of Natural Surfactant Phosphatidylcholine from 3-Day-Old Rabbit Lungs: Effects of Dose and Species

Abstract

ABSTRACT. Surfactants were labeled in vivo with ['HI choline and the large aggregates of the surfactant were recovered by alveolar wash and centrifugation. The labeled natural surfactants from rabbit, sheep, cat, and pig were injected into the airways of 3-day-old rabbits, and the percent recoveries of the labeled surfactant-associated phosphatidylcholine were measured in alveolar washes, lung tissue after alveolar wash, and in the lungs (alveolar wash plus lung tissue). The rabbit surfactant-associated phosphatidylcholine was cleared from the lungs at a constant 15.6 f 1. RDS, respiratory distress syndromeClinical trials using surfactants from animal sources for the treatment of RDS demonstrated acute improvements in pulmonary function, decreased pulmonary associated complications of RDS, and improved long-term outcomes (1-5). Clinical trials using synthetic surfactants documented less convincing responses (6, 7). The surfactants from animal sources were used in humans without apparent problems relating to cross-species sensitization (8). Several clinical trials documented prolonged responses of infants to single doses of surfactant, suggesting that the material remained within the lungs for a long period of time (2, 8). The rate of loss of small amounts of labeled species specific natural surfactant from the lungs of newborn rabbits and lambs was very slow relative to the rate of loss from adult rabbit lungs (9-1 1). Large doses of natural surfactant also were cleared slowly from developing rabbit lungs (1 2). However, the dependence of sur-

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

“…It could be due to differences in the rate of turnover in the alveoli or removal from the lungs, to a difference in the efficiency of recycling (as indicated by this study and previous experiments) or a combination of these mechanisms. On the whole, the kinetic behaviour of Curosurf DPPC, which is characterized by rapid turnover in the alveoli, recycling between alveoli and parenchyma and slow removal from the lung, is similar to that of DPPC present in natural surfactant [17,19].…”

“…This procedure was repeated with four more saline volumes and the five washes were pooled and brought to 25 mL with saline [19]. Usually, 92±4% (±SD) of the instilled fluid was recovered.…”

“…In previous studies it was found that labelled Surfactant TA (a surfactant derived from bovine lungs), administered into the trachea of premature and adult rabbits: 1) associates with the endogenous pools of surfactant soon after instillation; 2) remains in the lung for a long time; 3) does not change the endogenous synthesis of phosphatidylcholine or its secretion, even when administered as a treatment dose; and 4) does not accumulate within alveolar macrophages [17][18][19][20]. These studies suggested that exogenous surfactant could be recycled and indicated that macrophages play a minor role in surfactant catabolism.…”

Recovery of Treatment Doses of Surfactants from the Lungs and Vascular Compartments of Mechanically Ventilated Premature Rabbits

“…After receiving treatment doses of 75 mg/kg natural rabbit surfactant or calf surfactant, the rabbits cleared about 25% of the labeled phosphatidylcholine from their lungs over the 6-h study period. If they had maintained this clearance rate, they would have cleared the total treatment dose from their lungs by 24 h. This would be much more rapid than the phosphatidylcholine clearance rates of 10-1 5%/24 h reported for 3-d-old rabbits after administration of either tracer or treatment doses of natural rabbit or calf surfactant (6). In fact, the preterm rabbits in this study cleared natural surfactant phosphatidylcholine from the lungs at a rate of 4%/h, a value similar to the clearance rates of 3-4%/h reported previously in healthy, adult rabbits (4).…”

“…(Pediatr Res 25:423-428,1989) Abbreviations SP, surfactant-associated protein DPC, dipalmitoylphophatidylcholine Surfactant replacement therapy decreases the incidence and initial severity of respiratory distress syndrome in preterm infants (1-3). However, the clearance of exogenously administered surfactants has been studied primarily in healthy spontaneously breathing fullterm or adult animals (4)(5)(6)(7)(8). Preterm animals with respiratory distress syndrome requiring positive-pressure ventilation may not have the same low rates of surfactant clearance and high rates of reutilization as healthy fullterm animals.…”