Cumulative effects of repeated surfactant treatments in the rabbit.
The responses of the adult rabbit lung to multiple doses of surfactant after intratracheal injections of either natural calf surfactant or Surfactant-TA were evaluated. For each surfactant, four groups of 1.4-kg rabbits were studied: group 1 received 100 mg of surfactant containing isotopically-labeled dipalmitoylphosphatidylcholine; group 2 received the same labeled surfactant and then three tracheal injections of vehicle; group 3 received labeled surfactant and then three doses (100 mg) of unlabeled surfactant; group 4 was treated in the same way as group 3 except that the final dose was of the labeled surfactant. All rabbits were killed, and alveolar washes were recovered 24 h after the labeled surfactant dose had been given. The amount of labeled palmitate-saturated phosphatidylcholine (Sat PC) in alveolar washes did not change after multiple doses of calf surfactant, indicating that subsequent doses did not alter the clearance of previous doses. The four doses of calf surfactant increased the alveolar Sat PC pool size by a factor of 2.5 only when measured 6 h after the last dose, but the total lung Sat PC pool size doubled, indicating a loss of most of the surfactant Sat PC to the lung tissue. In contrast, Surfactant-TA increased the alveolar pool size by a factor of 4 after the single dose and by a factor of 11 after the multiple doses, and the percentage clearance of labeled Sat PC from the lungs decreased with multiple doses, indicating an effect of subsequent doses on the initial dose. The quantity of Sat PC cleared from the lungs increased by about a factor of 2 after the multiple doses of Surfactant-TA. Although repetitive surfactant doses changed alveolar and lung Sat PC pool sizes the quantity of Sat PC cleared from the lungs increased, and the lungs accommodated the large amount of surfactant without short-term adverse effects.
Pettenazzo
A
A
Perinatal Research Laboratories, Harbor-University of California at Los Angeles Medical Center, Torrance.
Jobe
A H
AH
Ikegami
M
M
Rider
E
E
Seidner
S R
SR
Yamada
T
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002417:Cattle; D002794:Choline; D005260:Female; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids; D010713:Phosphatidylcholines / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011817:Rabbits; D013501:Surface-Active Agents / Q000494:pharmacology
D010169:Palmitic Acids; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents; D019308:Palmitic Acid; D002794:Choline