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
Acute lung injury in the preterm newborns can originate from prematurity of the lung and insufficient synthesis of pulmonary surfactant. This situation is known as respiratory distress syndrome (RDS). In the term neonates, the respiratory insufficiency is related to a secondary inactivation of the pulmonary surfactant, for instance, by action of endotoxins in bacterial pneumonia or by effects of aspirated meconium. The use of experimental models of the mentioned situations provides new information on the pathophy siology of these disorders and offers unique possibility to test novel therapeutic approaches in the conditions which are very similar to the clinical syndromes. Herewith we review the advantages and limitations of the use of experimental models of RDS and meconium aspiration syndrome (MAS) and their value for clinics., D. Mokra, A. Calkovska., and Obsahuje bibliografii
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