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Division for Experimental Perinatal Pathology, Department of Woman and Child Health, Karolinska Institute, S-171 76 Stockholm; Department of Clinical Chemistry, Karolinska Hospital, S-171 76 Stockholm, Sweden; Department of Anesthesiology, Kanazawa University, Kanazawa 920; Department of Molecular Pathology, Kyoto University, Kyoto 606; and Department of Biochemistry, Sapporo Medical College, Sapporo 060, Japan
The purpose of this study was to characterize the toxic effects
of lysophosphatidylcholine (lyso-PC) on neonatal lung function. Various
doses of lyso-PC (from 0 to 40 mg/kg) were administered to near-term
newborn rabbits. Lung-thorax compliance during mechanical ventilation
was significantly decreased by doses
10 mg/kg, and static lung
volumes during deflation were decreased by doses
20 mg/kg. Using the
same experimental model, we investigated the effects of modified
porcine surfactant (Curosurf, 200 mg/kg). Animals exposed to lyso-PC at
birth and treated simultaneously with surfactant showed a satisfactory
therapeutic response, whereas those treated after 30 min failed to
respond. These animals also had a much larger leak of albumin into the
air spaces and an elevated minimum surface tension of the lavage fluid
in a pulsating bubble surfactometer, suggesting inactivation of the
exogenous surfactant. Timing of surfactant administration may thus be
essential for the therapeutic effect in this experimental model of
acute lung injury.
respiratory distress syndrome; animals; newborn; rabbits; respiratory mechanics; lung protein leakage
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