Metabolism of exogenously administered surfactant in the acutely injured lungs of adult rabbits.
Acute lung injury was induced in adult rabbits with a subcutaneous injection of N-nitro-so-N-methylurethane (NNNMU). Clearance of saturated phosphatidylcholine (Sat.PC) from a treatment dose of exogenous surfactant (100 mg/kg) in the injured lungs of these rabbits was similar to normal, control rabbits when measured 24 h after treatment. However, total Sat.PC pool sizes in both the alveolar wash and total lung at this time point were significantly lower for the injured lungs than for the control lungs (p less than 0.05), implying altered endogenous surfactant metabolism in response to surfactant treatment in the injured animals. Although both injured and control animals had comparable ratios of small to large surfactant aggregates, as measured by differential centrifugation of alveolar wash 5 min after treatment, by 24 h this ratio had increased 5-fold in the control animals and remained unchanged in the injured animals. This indicated diminished conversion of large surfactant aggregates to the smaller forms in lung injury. In vivo functional studies of these aggregates were performed by intratracheal injection into surfactant-deficient preterm rabbits. Large aggregates from normal adult rabbits given surfactant had superior functional properties than did the surfactant used for treatment alone, which in turn was better than large aggregates isolated from NNNMU-injured rabbits treated with surfactant. This indicates that the alveolar environment influenced the function of the exogenously administered surfactant differently in normal and injured rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Lewis
J F
JF
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance 90509.
Ikegami
M
M
Jobe
A H
AH
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D009605:Nitrosomethylurethane; D010713:Phosphatidylcholines / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits
D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D009605:Nitrosomethylurethane