The Effect of Modified Porcine Surfactant Alone or in Combination with Polymyxin B on Lung Homeostasis in LPS-Challenged and Mechanically Ventilated Adult Rats.

The study aimed to prove the hypothesis that exogenous surfactant and an antibiotic polymyxin B (PxB) can more effectively reduce lipopolysaccharide (LPS)-induced acute lung injury (ALI) than surfactant treatment alone, and to evaluate the effect of this treatment on the gene expression of surfactant proteins (SPs). Anesthetized rats were intratracheally instilled with different doses of LPS to induce ALI. Animals with LPS 500 µg/kg have been treated with exogenous surfactant (poractant alfa, Curosurf®, 50 mg PL/kg b.w.) or surfactant with PxB 1% w.w. (PSUR + PxB) and mechanically ventilated for 5 hrs. LPS at 500 µg/kg increased lung edema, oxidative stress, and the levels of proinflammatory mediators in lung tissue and bronchoalveolar lavage fluid (BALF). PSUR reduced lung edema and oxidative stress in the lungs and IL-6 in BALF. This effect was further potentiated by PxB added to PSUR. Exogenous surfactant enhanced the gene expression of SP-A, SP-B, and SP-C, however, gene expression for all SPs was reduced after treatment with PSUR + PxB. In mechanically ventilated rats with LPS-induced ALI, the positive effect of exogenous surfactant on inflammation and oxidative stress was potentiated with PxB. Due to the tendency for reduced SPs gene expression after surfactant/PxB treatment topical use of PxB should be considered with caution.

Recombinant Human Superoxide Dismutase and N-Acetylcysteine Addition to Exogenous Surfactant in the Treatment of Meconium Aspiration Syndrome.

This study aimed to evaluate the molecular background of N-acetylcysteine (NAC) and recombinant human superoxide dismutase (rhSOD) antioxidant action when combined with exogenous surfactant in the treatment of meconium aspiration syndrome (MAS), considering redox signalling a principal part of cell response to meconium. Young New Zealand rabbits were instilled with meconium suspension (Mec) and treated by surfactant alone (Surf) or surfactant in combination with i.v. NAC (Surf + NAC) or i.t. rhSOD (Surf + SOD), and oxygen-ventilated for 5 h. Dynamic lung-thorax compliance, mean airway pressure, PaO2/FiO2 and ventilation efficiency index were evaluated every hour; post mortem, inflammatory and oxidative markers (advanced oxidation protein products, total antioxidant capacity, hydroxynonenal (HNE), p38 mitogen activated protein kinase, caspase 3, thromboxane, endothelin-1 and secretory phospholipase A2) were assessed in pulmonary tissue homogenates. rhSOD addition to surfactant improved significantly, but transiently, gas exchange and reduced levels of inflammatory and oxidative molecules with higher impact; Surf + NAC had stronger effect only on HNE formation, and duration of treatment efficacy in respiratory parameters. In both antioxidants, it seems that targeting reactive oxygen species may be strong supporting factor in surfactant treatment of MAS due to redox sensitivity of many intracellular pathways triggered by meconium.