Efficacy of intratracheal budesonide-surfactant combined therapy in surfactant-insufficient rat lungs with lipopolysaccharide insult.

Abstract

Intratracheal steroid therapy for lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains challenging particularly in surfactant-insufficient lungs, a common problem of neonatal or pediatric ALI. 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-insufficient rat lungs. 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 (NS-BUD; BUD in saline), DS-BUD (BUD in diluted surfactant), FS-BUD (BUD in full-strength surfactant), FS (full-strength surfactant). Cardiopulmonary variables were monitored 4 hours post injury. Histological and immunohistochemical assessments of the lungs were performed. The FS-BUD and FS groups presented better gas exchange, less metabolic acidosis, less oxygen index, and more stable hemodynamic changes than the DS-BUD, NS-BUD, and control groups. The total lung injury scores assessed by histological examination were ordered as follows: FS-BUD < DS-BUD or FS < NS-BUD < control. The immunostaining intensities of lung myeloperoxidase showed the following order: NS-BUD, DS-BUD, or FS-BUD < control or FS. Only the FS-BUD group displayed a smaller immunostaining intensity of lung tumor necrosis factor (TNF)-α than the control group. Among our therapeutic strategies, intratracheal BUD delivered by full-strength surfactant confers an optimal protection against LPS-induced ALI in surfactant-insufficient rat lungs.