Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung damage, inflammation, oedema formation, and surfactant dysfunction leading to hypoxemia. Severe ARDS can accelerate the injury of other organs, worsening the patient ́s status. There is an evidence that the lung tissue injury affects the right heart function causing cor pulmonale. However, heart tissue changes associated with ARDS are still poorly known. Therefore, this study evaluated oxidative and inflammatory modifications of the heart tissue in two experimental models of ARDS induced in New Zealand rabbits by intratracheal instillation of neonatal meconium (100 mg/kg) or by repetitive lung lavages with saline (30 ml/kg). Since induction of the respiratory insufficiency, all animals were oxygen-ventilated for next 5 h. Total and differential counts of leukocytes were measured in the arterial blood, markers of myocardial injury [(troponin, creatine kinase - myocardial band (CK-MB), lactate dehydrogenase (LD)] in the plasma, and markers of inflammation [tumour necrosis factor (TNF)alpha, interleukin (IL)-6], cardiovascular risk [galectin-3 (Gal-3)], oxidative changes [thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine (3NT)], and vascular damage [receptor for advanced glycation end products (RAGE)] in the heart tissue. Apoptosis of heart cells was investigated immunohistochemically. In both ARDS models, counts of total leukocytes and neutrophils in the blood, markers of myocardial injury, inflammation, oxidative and vascular damage in the plasma and heart tissue, and heart cell apoptosis increased compared to controls. This study indicates that changes associated with ARDS may contribute to early heart damage what can potentially deteriorate the cardiac function and contribute to its failure.

• MeSH
• apoptóza fyziologie   MeSH
• biologické markery metabolismus   MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• oxidační stres fyziologie   MeSH
• poranění srdce metabolismus   patologie   MeSH
• poškození plic metabolismus   patologie   MeSH
• syndrom aspirace mekonia metabolismus   patologie   MeSH
• syndrom dechové tísně metabolismus   patologie   MeSH
• zánět metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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 pathophysiology 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.

• MeSH
• akutní poškození plic metabolismus   patofyziologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• novorozenec MeSH
• syndrom aspirace mekonia metabolismus   patofyziologie   MeSH
• syndrom respirační tísně novorozenců metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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-alpha) 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.

• MeSH
• antiflogistika aplikace a dávkování   MeSH
• budesonid aplikace a dávkování   MeSH
• kombinovaná farmakoterapie MeSH
• králíci MeSH
• mediátory zánětu antagonisté a inhibitory   metabolismus   MeSH
• modely nemocí na zvířatech * MeSH
• oxidační stres účinky léků   fyziologie   MeSH
• peroxidace lipidů účinky léků   fyziologie   MeSH
• plicní surfaktanty aplikace a dávkování   MeSH
• syndrom aspirace mekonia farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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, N-acetylcysteine (NAC) alone or by their combination and oxygen-ventilated 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, PaO(2)/FiO(2)) 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-beta formation and thus seems to be favorable agent for improving surfactant therapy in MAS.

• MeSH
• acetylcystein farmakologie   terapeutické užití   MeSH
• bronchoalveolární lavážní tekutina imunologie   MeSH
• cytokiny metabolismus   MeSH
• edém prevence a kontrola   MeSH
• expektorancia farmakologie   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• králíci MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• pilotní projekty MeSH
• plíce účinky léků   metabolismus   MeSH
• plicní surfaktanty farmakologie   terapeutické užití   MeSH
• počet leukocytů MeSH
• preklinické hodnocení léčiv MeSH
• respirační funkční testy MeSH
• syndrom aspirace mekonia imunologie   metabolismus   prevence a kontrola   MeSH
• testy migrace leukocytů MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH