The inflammation present in acute respiratory distress syndrome (ARDS) and thereby associated injury to the alveolar-capillary membrane and pulmonary surfactant can potentiate respiratory failure. Even considering the high mortality rate of severe ARDS, glucocorticoids appear to be a reasonable treatment option along with an appropriate route of delivery to the distal lung. This study aimed to investigate the effect of budesonide therapy delivered intratracheally by high-frequency oscillatory ventilation (HFOV) on lung function and inflammation in severe ARDS. Adult New Zealand rabbits with respiratory failure (P/F<13.3 kPa) induced by intratracheal instillation of hydrochloric acid (HCl, 3 ml/kg, pH 1.5) followed by high tidal ventilation (VT 20 ml/kg) to mimic ventilator-induced lung injury (VILI) were treated with intratracheal bolus of budesonide (0.25 mg/kg, Pulmicort) delivered by HFOV (frequency 8 Hz, MAP 1 kPa, deltaP 0.9 kPa). Saline instead of HCl without VILI with HFOV delivered air bolus instead of therapy served as healthy control. All animals were subjected to lung-protective ventilation for 4 h, and respiratory parameters were monitored regularly. Postmortem, lung injury, wet-to-dry weight ratio, leukocyte shifts, and levels of cytokines in plasma and lung were evaluated. Budesonide therapy improved the lung function (P/F ratio, oxygenation index, and compliance), decreased the cytokine levels, reduced lung edema and neutrophils influx into the lung, and improved lung architecture in interstitial congestion, hyaline membrane, and atelectasis formation compared to untreated animals. This study indicates that HFOV delivered budesonide effectively ameliorated respiratory function, and attenuated acid-induced lung injury in a rabbit model of severe ARDS.

• MeSH
• budesonid MeSH
• cytokiny MeSH
• králíci MeSH
• poškození plic * MeSH
• respirační insuficience * MeSH
• syndrom dechové tísně * chemicky indukované   terapie   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• budesonid MeSH
• cytokiny MeSH

The development of acute respiratory distress syndrome (ARDS) is known to be independently attributable to aspiration-induced lung injury. Mechanical ventilation as a high pressure/volume support to maintain sufficient oxygenation of a patient could initiate ventilator-induced lung injury (VILI) and thus contribute to lung damage. Although these phenomena are rare in the clinic, they could serve as the severe experimental model of alveolar-capillary membrane deterioration. Lung collapse, diffuse inflammation, alveolar epithelial and endothelial damage, leakage of fluid into the alveoli, and subsequent inactivation of pulmonary surfactant, leading to respiratory failure. Therefore, exogenous surfactant could be considered as a therapy to restore lung function in experimental ARDS. This study aimed to investigate the effect of modified porcine surfactant in animal model of severe ARDS (P/F ratio

• MeSH
• edém MeSH
• králíci MeSH
• kyselina chlorovodíková toxicita   terapeutické užití   MeSH
• plíce MeSH
• plicní surfaktanty * terapeutické užití   farmakologie   MeSH
• poškození plic mechanickou ventilací * farmakoterapie   MeSH
• povrchově aktivní látky farmakologie   terapeutické užití   MeSH
• prasata MeSH
• syndrom dechové tísně * chemicky indukované   farmakoterapie   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina chlorovodíková MeSH
• plicní surfaktanty * MeSH
• povrchově aktivní látky MeSH

In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.

• MeSH
• angiotensin konvertující enzym 2 metabolismus   MeSH
• COVID-19 imunologie   metabolismus   virologie   MeSH
• farmakoterapie COVID-19 MeSH
• interakce hostitele a patogenu MeSH
• internalizace viru MeSH
• lidé MeSH
• plíce účinky léků   imunologie   metabolismus   virologie   MeSH
• plicní surfaktanty terapeutické užití   MeSH
• pneumocyty účinky léků   imunologie   metabolismus   virologie   MeSH
• proteiny asociované s plicním surfaktantem metabolismus   MeSH
• SARS-CoV-2 imunologie   patogenita   MeSH
• serinové endopeptidasy metabolismus   MeSH
• virové receptory metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ACE2 protein, human MeSH Prohlížeč
• angiotensin konvertující enzym 2 MeSH
• plicní surfaktanty MeSH
• proteiny asociované s plicním surfaktantem MeSH
• serinové endopeptidasy MeSH
• TMPRSS2 protein, human MeSH Prohlížeč
• virové receptory MeSH

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
• Názvy látek
• biologické markery MeSH

Inflammation associated with acute respiratory distress syndrome (ARDS) can damage the alveolar epithelium and surfactant and worsen the respiratory failure. Glucocorticoids (GC) appear to be a rational therapeutic approach, but the effect is still unclear, especially for early administration and low-dose. In this study we compared two low doses of dexamethasone in early phase of surfactant-depleted model of acute respiratory distress syndrome (ARDS). In the study, lung-lavaged New Zealand rabbits with respiratory failure (PaO(2)<26.7 kPa in FiO(2) 1.0) were treated with intravenous dexamethasone (DEX): 0.5 mg/kg (DEX-0.5) and 1.0 mg/kg (DEX-1.0), or were untreated (ARDS). Animals without ARDS served as controls. Respiratory parameters, lung edema, leukocyte shifts, markers of inflammation and oxidative damage in the plasma and lung were evaluated. Both doses of DEX improved the lung function vs. untreated animals. DEX-1.0 had faster onset with significant improvement in gas exchange and ventilation efficiency vs. DEX-0.5. DEX-1.0 showed a trend to reduce lung neutrophils, local oxidative damage, and levels of TNFalpha, IL-6, IL-8 more effectively than DEX-0.5 vs. ARDS group. Both dosages of dexamethasone significantly improved the lung function and suppressed inflammation in early phase ARDS, while some additional enhancement was observed for higher dose (1 mg/kg) of DEX.

• MeSH
• antiflogistika aplikace a dávkování   MeSH
• bronchoalveolární lavážní tekutina cytologie   MeSH
• dexamethason aplikace a dávkování   MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• plíce účinky léků   MeSH
• počet leukocytů MeSH
• preklinické hodnocení léčiv MeSH
• respirační funkční testy MeSH
• syndrom dechové tísně krev   farmakoterapie   imunologie   MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• dexamethason MeSH

Pulmonary surfactant has a relaxing effect on the airway smooth muscle (ASM), which suggests its role in the pathogenesis of respiratory diseases associated with hyperreactivity of the ASM, such as asthma and chronic obstructive pulmonary disease (COPD). The ASM tone may be directly or indirectly modified by bacterial wall component lipopolysaccharide (LPS). This study elucidated the effect of LPS on the ASM reactivity and the role of surfactant in this interaction. The experiments were performed using ASM of adult guinea pigs by in vitro method of tissue organ bath (ASM unexposed-healthy or exposed to LPS under in vitro conditions) and ASM of animals intraperitoneally injected with LPS at a dose 1 mg/kg of b.w. once a day during 4-day period. Variable response of LPS was controlled by cyclooxygenase inhibitor indomethacin and relaxing effect of exogenous surfactant was studied using leukotriene and histamine receptor antagonists. The exogenous surfactant has relaxing effect on the ASM, but does not reverse LPS-induced smooth muscle contraction. The results further indicate participation of prostanoids and potential involvement of leukotriene and histamine H1 receptors in the airway smooth muscle contraction during LPS exposure.

• MeSH
• acetáty MeSH
• chinoliny MeSH
• cyklopropany MeSH
• hladké svalstvo účinky léků   MeSH
• lipopolysacharidy MeSH
• morčata MeSH
• plicní surfaktanty farmakologie   MeSH
• pyrilamin MeSH
• relaxace svalu účinky léků   MeSH
• sulfidy MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty MeSH
• chinoliny MeSH
• cyklopropany MeSH
• lipopolysacharidy MeSH
• montelukast MeSH Prohlížeč
• plicní surfaktanty MeSH
• pyrilamin MeSH
• sulfidy MeSH

Damage of alveolar-capillary barrier, inflammation, oxidative injury, and lung cell apoptosis represent the key features of acute lung injury (ALI). This study evaluated if selective phosphodiesterase (PDE)-4 inhibitor roflumilast can reduce the mentioned changes in lavage-induced model of ALI. Rabbits with ALI were divided into 2 groups: ALI without therapy (A group) and ALI treated with roflumilast i.v. (1 mg/kg; A+R group). One group of healthy animals without ALI served as ventilated controls (C group). All animals were oxygen-ventilated for further 4 h. At the end of experiment, total and differential counts of cells in bronchoalveolar lavage fluid (BALF) and total and differential counts of white blood cells were estimated. Lung edema formation was assessed from determination of protein content in BALF. Pro-inflammatory cytokines (TNFalpha, IL-6 and IL-8) and markers of oxidation (3-nitrotyrosine, thiobarbituric-acid reactive substances) were detected in the lung tissue and plasma. Apoptosis of lung cells was investigated immunohistochemically. Treatment with roflumilast reduced leak of cells, particularly of neutrophils, into the lung, decreased concentrations of cytokines and oxidative products in the lung and plasma, and reduced lung cell apoptosis and edema formation. Concluding, PDE4 inhibitor roflumilast showed potent anti-inflammatory actions in this model of ALI.

• MeSH
• akutní poškození plic farmakoterapie   metabolismus   MeSH
• aminopyridiny farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   fyziologie   MeSH
• benzamidy farmakologie   terapeutické užití   MeSH
• bronchoalveolární lavážní tekutina MeSH
• cyklopropany farmakologie   terapeutické užití   MeSH
• inhibitory fosfodiesterasy 4 farmakologie   terapeutické užití   MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• oxidační stres účinky léků   fyziologie   MeSH
• pneumonie farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminopyridiny MeSH
• benzamidy MeSH
• cyklopropany MeSH
• inhibitory fosfodiesterasy 4 MeSH
• Roflumilast MeSH Prohlížeč

Meconium aspiration syndrome (MAS) in newborns is characterized mainly by respiratory failure due to surfactant dysfunction and inflammation. Previous meta-analyses did not prove any effect of exogenous surfactant treatment nor glucocorticoid administration on final outcome of children with MAS despite oxygenation improvement. As we supposed there is the need to intervene in both these fields simultaneously, we evaluated therapeutic effect of combination of exogenous surfactant and selective inhibitor of NF-kappaB (IKK-NBD peptide). Young New Zealand rabbits were instilled by meconium suspension and treated by surfactant alone or surfactant in combination with IKK-NBD, and oxygen-ventilated for 5 h. PaO(2)/FiO(2), oxygenation index, oxygen saturation and ventilation efficiency index were evaluated every hour; post mortem, total and differential leukocyte counts were investigated in bronchoalveolar lavage fluid (BALF) and inflammatory, oxidative and apoptotic markers were assessed in lung tissue homogenates. Exogenous surfactant combined with IKK-NBD improved oxygenation, reduced neutrophil count in BALF and levels of IL-1beta, IL-6, p38 MAPK and caspase 3 in comparison with surfactant-only therapy. It seems that inhibition of inflammation may be strong supporting factor in surfactant treatment of MAS.

• MeSH
• králíci MeSH
• mediátory zánětu antagonisté a inhibitory   metabolismus   MeSH
• mekonium * MeSH
• náhodné rozdělení MeSH
• NF-kappa B antagonisté a inhibitory   metabolismus   MeSH
• novorozená zvířata MeSH
• plicní surfaktanty farmakologie   terapeutické užití   MeSH
• poškození plic chemicky indukované   farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mediátory zánětu MeSH
• NF-kappa B MeSH
• plicní surfaktanty MeSH

Acute lung injury (ALI) is associated with deterioration of alveolar-capillary lining and transmigration and activation of inflammatory cells. Whereas a selective phosphodiesterase-4 (PDE4) inhibitor roflumilast has exerted potent anti-inflammatory properties, this study evaluated if its intravenous delivery can influence inflammation, edema formation, and respiratory parameters in rabbits with a lavage-induced model of ALI. ALI was induced by repetitive saline lung lavage (30 ml/kg). Animals were divided into 3 groups: ALI without therapy (ALI), ALI treated with roflumilast i.v. (1 mg/kg; ALI+Rofl), and healthy ventilated controls (Control), and were ventilated for following 4 h. Respiratory parameters (blood gases, ventilatory pressures, lung compliance, oxygenation indexes etc.) were measured and calculated regularly. At the end of experiment, animals were overdosed by anesthetics. Total and differential counts of cells in bronchoalveolar lavage fluid (BAL) were estimated microscopically. Lung edema was expressed as wet/dry lung weight ratio. Treatment with roflumilast reduced leak of cells (P<0.01), particularly of neutrophils (P<0.001), into the lung, decreased lung edema formation (P<0.01), and improved respiratory parameters. Concluding, the results indicate a future potential of PDE4 inhibitors also in the therapy of ALI.

• MeSH
• akutní poškození plic farmakoterapie   etiologie   patofyziologie   MeSH
• aminopyridiny aplikace a dávkování   MeSH
• benzamidy aplikace a dávkování   MeSH
• bronchoalveolární laváž škodlivé účinky   MeSH
• bronchoalveolární lavážní tekutina MeSH
• chlorid sodný toxicita   MeSH
• cyklopropany aplikace a dávkování   MeSH
• inhibitory fosfodiesterasy 4 aplikace a dávkování   MeSH
• intravenózní podání MeSH
• králíci MeSH
• modely nemocí na zvířatech * MeSH
• plíce účinky léků   fyziologie   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminopyridiny MeSH
• benzamidy MeSH
• chlorid sodný MeSH
• cyklopropany MeSH
• inhibitory fosfodiesterasy 4 MeSH
• Roflumilast MeSH Prohlížeč

The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells and pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below.

• MeSH
• akutní poškození plic chemicky indukované   metabolismus   MeSH
• biologické přípravky antagonisté a inhibitory   metabolismus   MeSH
• fosfolipidy antagonisté a inhibitory   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy metabolismus   toxicita   MeSH
• plíce účinky léků   metabolismus   MeSH
• plicní surfaktanty antagonisté a inhibitory   metabolismus   MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické přípravky MeSH
• fosfolipidy MeSH
• lipopolysacharidy MeSH
• plicní surfaktanty MeSH
• poractant alfa MeSH Prohlížeč