Severe meconium aspiration sy ndrome (MAS) in newborns is often treated by exogenous surfac tant. Because its efficacy is reduced by meconium-induced inflammation, glucocorticoid budesonide was added into surfac tant preparation Curosurf to enhance efficacy of the surfactant therapy in experimental model of MAS. Oxygen-ventilated rabbits were intratracheally given meconium (25 mg/ml, 4 ml/kg) to induce respiratory failure. Thirty minutes later, animals were treated by intratracheal budesonide (0.25 mg/kg) ; or surfactant lung lavage (10 ml/kg, 5 mg phospholipids/ml) repeated twice, followed by undiluted Curosurf (100 mg phospholipids/kg) ; or by the above mentioned surfactant treatment with the last surfactant dose fortified with budesonide (0.25 mg/kg) ; or were untreated. Animals were ventilated for additional 5 hours and respiratory parameters were measured regularly. After sacrificing animals, wet-dry lung weight ratio was evaluated and plasma levels of interleukins (IL)-1beta, -6, -8, and TNF-alpha were measured by ELISA method. Efficacy of the given therapies to enhance lung functions and to diminish lung edema formation and in flammation increased from budesonide-only and surf actant-only therapy to surfactant+budesonide therapy. Combined therapy improved gas exchange from 30 min of administration, and showed a longer- lasting effect than surfactant-only therapy. In conclusions, budesonide additionally improv ed the effects of exogenous surfactant in experimental MAS., P. Mikolka ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was
prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5
h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/
proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-
α) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.
Meconium aspiration syndrome (MAS) is meconium-induced respiratory failure of newborns associated with activation of inflammatory and oxidative pathways. For severe MAS, exogenous surfactant treatment is used which improves respiratory functions but does not treat the inflammation. Oxidative process can lead to later surfactant inactivation; hence, surfactant combination with antioxidative agent may enhance the therapeutic effect. Young New Zealand rabbits were instilled by meconium suspension and treated by surfactant alone, Nacetylcysteine (NAC) alone or by their combination and oxygenventilated for 5 h. Blood samples were taken before and 30 min after meconium application and 30 min, 1, 3 and 5 h after the treatment for evaluating of oxidative damage, total leukocyte count, leukocyte differential count and respiratory parameters. Leukocyte differential was assessed also in bronchoalveolar lavage fluid. NAC alone had only mild therapeutic effect on MAS. However, the combination of NAC and surfactant facilitated rapid onset of therapeutic effect in respiratory parameters (oxygenation index, PaO2/FiO2) compared to surfactant alone and was the only treatment which prevented neutrophil migration into the lungs, oxidative damage and lung edema. Moreover, NAC suppressed IL-8 and IL-β formation and thus seems to be favorable agent for improving surfactant therapy in MAS., J. Kopincová, D. Mokrá, P. Mikolka, M. Kolomazník, A. Čalkovská., and Obsahuje bibliografii