Purpose: To test whether inhalation of the phosphodiesterase 3 inhibitor milrinone may attenuate experimental acute lung injury (ALI).
Methods: In rats, ALI was induced by infusion of oleic acid (OA). After 30 min, milrinone was inhaled either as single dose, or repeatedly in 30 min intervals. In mice, ALI was induced by intratracheal instillation of hydrochloric acid, followed by a single milrinone inhalation.
Results: Four hours after OA infusion, ALI was evident as lung inflammation, protein-rich edema and hypoxemia. A single inhalation of milrinone attenuated the increase in lung wet-to-dry weight ratio and myeloperoxidase activity, and reduced protein concentration, neutrophil counts and TNF-alpha levels in bronchoalveolar lavage. This effect was further pronounced when milrinone was repeatedly inhaled. In mice with acid-induced ALI, milrinone attenuated hypoxemia and prevented the increase in lung myeloperoxidase activity.
Conclusions: Inhalation of aerosolized milrinone may present a novel therapeutic strategy for the treatment of ALI.