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 =13.3 kPa) induced by intratracheal instillation of hydrochloric acid (HCl, 3 ml/kg, pH 1.25) followed by VILI (V(T) 20 ml/kg). Adult rabbits were divided into three groups: untreated ARDS, model treated with a bolus of poractant alfa (Curosurf®, 2.5 ml/kg, 80 mg phospholipids/ml), and healthy ventilated animals (saline), which were oxygen-ventilated for an additional 4 h. The lung function parameters, histological appearance, degree of lung edema and levels of inflammatory and oxidative markers in plasma were evaluated. Whereas surfactant therapy with poractant alfa improved lung function, attenuated inflammation and lung edema, and partially regenerated significant changes in lung architecture compared to untreated controls. This study indicates a potential of exogenous surfactant preparation in the treatment of experimental ARDS.
- 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
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.
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
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
Pľúcny surfaktant je aktívny lipoproteinový komplex produkovaný v alveolárnych bunkách II. typu. ARDS je charakterizovaná vážnym akútnym poškodením pľúcnych funkcií. Ochorenie bolo pôvodne pomenované ako respiračná tieseň dospelých, teraz sa preferuje názov akútna respiračná tieseň. Iným názvom sú šokové pľúca. U ARDS dochádza k extenzívnemu poškodeniu biochemických a biofyzikálnych vlastností pľúcneho surfaktantu. Zatiaľ iba niekoľko štúdií popísalo, že exogénny surfaktant u ARDS zlepšuje oxygenáciu, pľúcnu mechaniku a aj prežívanie. Bronchoskopická instilácia surfaktantu dovoľuje klinikovi vykonávať aj bronchoalveolárnu laváž (BAL) k odstráneniu zápalových mediátorov. V kazuistike opisujeme naše prvé skúsenosti.
Pulmonary surfactant is active lipoprotein complex formed by type II alveolar cells. Acute Respiratory Distress Syndrome (ARDS) is charakterized by serious acute respiratory failure. The disease was initialy called Adult Respiratory Distress Syndrome, now it is called as Acute Respiratory Distress Syndrome. Another name for ARDS is shock lung. Extensive biochemical £ind biophysical changes of the pulmonary surfactant occur in the ARDS. Only a few reports have shown that exogenous surfactant administration in ARDS can improve oxygenation, lung mechanics and survival. Bronchoscopic instillation of surfactant also allows the clinician to perform a bronchoalveolar lavage (BAL) to remove inflammatory mediators. In case report we describe our first experiences.
Cílem práce je podat aktuální informace o indukci plicní zralosti plodu kortikoidy, které lze aplikovat do klinické praxe. Článek odpovídá na následující otázky: kdo je ideální kandidátkou k podání kortikoidů, kdy podat kortikoidy, jaké jsou kontraindikace podání kortikoidů, kortikosteroidy a předčasný odtok plodové vody, má se kůra kortikoidy opakovat?
Guideline for use antenatal corticosteroids for fetal lung maturation in clinical practice is presented. Following clinical questions are answered: Who is ideal candidate for corticosteroids use, when corticosteroids should be applied, which drug is the best, are there some contraindications, should be treatment repeated.
V období od 1. 5. 1994 do 31. 12. 1997 se na I. a II. gynek.-porod. klinice MU v Brně narodilo 311novorozenců ve váhových kategoriích 500 až 2 000 g. Byla provedena retrospektivní studie srov-návající neonatální výsledky tří metod prenatální indukce zrání surfaktantu u předčasně naroze-ných novorozenců. První skupina byla bez terapie, ve druhé byl aplikován pouze betametazona ve třetí betametazon a tyrotropin releasing hormon (TRH). Novorozenci byli dále členěni do tříváhových kategorií: 500 - 999 g, 1 000 - 1 499 g a 1 500 g a více.Nejpříznivějších výsledků s aplikací betametazonu a TRH bylo dosaženo ve skupině novorozencůváhové kategorie 500 - 999 g. Ty se týkaly menšího počtu poporodní aplikace surfaktantu, sníženíoxygenačního indexu a doby umělé plicní ventilace, IV. stupně RDS a dalších sledovaných kompli-kací dítěte. Ve skupině novorozenců 1 000 - 1 499 g příznivě ovlivnila aplikace betametazonua TRH pouze oxygenační index a stupeň RDS. Ve skupině novorozenců nad 1 500 g nebyly již mezipopsanými třemi skupinami statisticky významné rozdíly.Závěrem lze konstatovat, že nejvyšší účinnosti bylo dosaženo kombinací betametazonu a TRHu novorozenců váhové kategorie 500 - 999 g, méně účinná byla tato kombinace ve skupině 1 000 - 1 499 ga zcela bez účinku ve skupině 1 500 g a více.
During the period from May 1. 1994 till December 31. 1997 at the First and SecondDepartments of Gynaecology and Obstetrics Masaryk University Brno 311 neonates with birthwe-ights from 500 to 2000 g were born. A retrospective study was made comparing neonatal results ofthree methods of prenatal induction of maturing of surfactant in premature neonates. The firstgroup was without treatment, in the second group only betamethasone was administered and inthe third group betamethasone and thyrotropin releasing hormone (TRH). The neonates weredivided into three body weight groups: 500 - 999 g, 1000 - 1499 g and 1500 g and more.The most favourable results with administration of betamethasone and TRH were obtained in thegroup weighing 500 - 999 g. This pertained to the smaller number of post-partum administrationof surfactant, reduction of the oxygenation index and period of artificial pulmonary ventilation.IVth grade RDS and other complications in the child. In the group of neonates weighing 1000 -1499 g administration of betamethasone and TRH had a positive effect only on the oxygenationindex and grade of RDS. In the group of neonates with weights above 1500 there were no statisti-cally significant differences between the described three groups.It may be concluded that the greatest effectiveness was achieved by a combination of betametha-sone and TRH in neonates weighing 500 - 999 g, this combination was less effective in the groupweighing 1000 - 1499 g and without effect in those weighing 1500 g or more.
- MeSH
- betamethason farmakologie MeSH
- dítě MeSH
- hormon uvolňující thyreotropin farmakologie MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec s nízkou porodní hmotností fyziologie klasifikace MeSH
- novorozenec MeSH
- plíce fyziologie MeSH
- plicní surfaktanty farmakologie MeSH
- porodní hmotnost MeSH
- předčasný porod MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- srovnávací studie MeSH
- Klíčová slova
- ALVEOFACT R R (BOEHRINGER INGELHEIM S.R.O),
- MeSH
- dítě MeSH
- farmakoterapie MeSH
- lidé MeSH
- nemoci novorozenců farmakoterapie MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- plicní surfaktanty farmakologie nedostatek terapeutické užití MeSH
- syndrom respirační tísně novorozenců farmakoterapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- novorozenec MeSH
- Klíčová slova
- ALVEOFACT R R (BOEHRINGER INGELHEIM S.R.O.),
- MeSH
- dítě MeSH
- hodnocení léčiv MeSH
- kojenecká mortalita MeSH
- lidé MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- plicní surfaktanty aplikace a dávkování farmakologie terapeutické užití MeSH
- respirační insuficience farmakoterapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- novorozenec MeSH
- Geografické názvy
- Německo západní MeSH