Abstract (250 words)
Objectives: Intratracheal steroid therapy for
lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains
challenging particularly in surfactant-deficiency lungs, a common
problem of preterm infants. Surfactant has been used as a vehicle for
intratracheal steroid in the treatment of other types of ALI. This study
investigated the efficacy of intratracheal budesonide (BUD) delivered by
two concentrations of surfactant in the treatment of LPS-induced ALI in
surfactant-insufficiency rat lungs.
Methods: Male adult rats were anesthetized and ventilated. Our
ALI model was established by repeated saline lavage to produce
surfactant insufficiency, followed by intratracheal LPS instillation.
Five study groups (n=5 for each) with different intratracheal treatments
following ALI were used: Control (no treatment), BUD (IT-NS-BUD; BUD in
saline); IT-DS-BUD (BUD in diluted surfactant); IT-FS-BUD (BUD in
full-strength surfactant); IT-FS (full-strength surfactant).
Cardiopulmonary variables were monitored 4 h post injury. Histological
and immunohistochemical assessments of the lungs were performed.
Results: The IT-FS-BUD and IT-FS groups presented better gas
exchange, less metabolic acidosis, less oxygen index, and more stable
hemodynamic changes than the IT-DS-BUD, IT-NS-BUD, and Control groups.
The total lung injury scores assessed by histological examination were
ordered as follows: IT-FS-BUD < IT-DS-BUD or IT-FS <
IT-NS-BUD < Control. The immunostaining intensities of lung
myeloperoxidase showed the following order: IT-NS-BUD, IT-DS-BUD, or
IT-FS-BUD < Control or IT-FS. Only the IT-FS-BUD group
displayed a smaller immunostaining intensity of lung TNF-α than the
control group.
Conclusion: Among our therapeutic strategies, intratracheal BUD
delivered by full-strength surfactant confers an optimal protection
against LPS-induced ALI in surfactant-insufficiency rat lungs.
Keywords: budesonide, surfactant, intratracheal instillation,
surfactant-deficiency, lipopolysaccharide, acute lung injury