Anti-inflammatory treatment in dysfunction of pulmonary surfactant in meconium-induced acute lung injury.

Abstract

Inflammation, oxidation, lung edema, and other factors participate in surfactant dysfunction in meconium aspiration syndrome (MAS). Therefore, we hypothesized that anti-inflammatory treatment may reverse surfactant dysfunction in the MAS model. Oxygen-ventilated rabbits were given meconium intratracheally (25 mg/ml, 4 ml/kg; Mec) or saline (Sal). Thirty minutes later, meconium-instilled animals were treated by glucocorticoids budesonide (0.25 mg/kg, i.t.) and dexamethasone (0.5 mg/kg, i.v.), or phosphodiesterase inhibitors aminophylline (2 mg/kg, i.v.) and olprinone (0.2 mg/kg, i.v.), or the antioxidant N-acetylcysteine (10 mg/kg, i.v.). Healthy, non-ventilated animals served as controls (Con). At the end of experiments, left lung was lavaged and a differential leukocyte count in sediment was estimated. The supernatant of lavage fluid was adjusted to a concentration of 0.5 mg phospholipids/ml. Surfactant quality was evaluated by capillary surfactometer and expressed by initial pressure and the time of capillary patency. The right lung was used to determine lung edema by wet/dry (W/D) weight ratio. Total antioxidant status (TAS) in blood plasma was evaluated. W/D ratio increased and capillary patency time shortened significantly, whereas the initial pressure increased and TAS decreased insignificantly in Sal vs. Con groups. Meconium instillation potentiated edema formation and neutrophil influx into the lungs, reduced capillary patency and TAS, and decreased the surfactant quality compared with both Sal and Con groups (p > 0.05). Each of the anti-inflammatory agents reduced lung edema and neutrophil influx into the lung and partly reversed surfactant dysfunction in the MAS model, with a superior effect observed after glucocorticoids and the antioxidant N-acetylcysteine.

• Authors: D Mokra, A Drgova, J Kopincova, R Pullmann, A Calkovska
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 756 Pg. 189-96 ( 2013) ISSN: 0065-2598 [Print] United States
• PMID: 22836635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Imidazoles
• Phosphodiesterase Inhibitors
• Pulmonary Surfactants
• Pyridones
• Aminophylline
• olprinone
• Budesonide
• Dexamethasone
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Acute Lung Injury (blood, drug therapy, etiology)
• Aminophylline (therapeutic use)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antioxidants (therapeutic use)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Budesonide (therapeutic use)
• Dexamethasone (therapeutic use)
• Disease Models, Animal
• Humans
• Imidazoles (therapeutic use)
• Infant, Newborn
• Leukocyte Count
• Lung (immunology, physiopathology)
• Meconium
• Meconium Aspiration Syndrome (blood, drug therapy, physiopathology)
• Neutrophils (immunology)
• Oxidative Stress
• Phosphodiesterase Inhibitors (therapeutic use)
• Pulmonary Edema
• Pulmonary Surfactants
• Pyridones (therapeutic use)
• Rabbits