scholarly journals Lung Inflammatory and Oxidative Alterations After Exogenous Surfactant Therapy Fortified With Budesonide in Rabbit Model of Meconium Aspiration Syndrome

2016 ◽  
pp. S653-S662 ◽  
Author(s):  
P. MIKOLKA ◽  
J. KOPINCOVÁ ◽  
P. KOŠÚTOVÁ ◽  
D. ČIERNY ◽  
A. ČALKOVSKÁ ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Expression Profiles ◽  
Rabbit Model ◽  
Weight Ratio ◽  
Meconium Aspiration Syndrome ◽  
Exogenous Surfactant ◽  
Lung Edema ◽  
Edema Formation ◽  
Meconium Aspiration ◽  
Cell Counts

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.

scholarly journals Budesonide Added to Modified Porcine Surfactant Curosurf May Additionally Improve the Lung Functions in Meconium Aspiration Syndrome

2013 ◽  
pp. S191-S200 ◽  
Author(s):  
P. MIKOLKA ◽  
D. MOKRÁ ◽  
J. KOPINCOVÁ ◽  
L. TOMČÍKOVÁ-MIKUŠIAKOVÁ ◽  
A. ČALKOVSKÁ
Keyword(s):  
Combined Therapy ◽  
Weight Ratio ◽  
Lung Lavage ◽  
Meconium Aspiration Syndrome ◽  
Exogenous Surfactant ◽  
Lung Edema ◽  
Lung Weight ◽  
Edema Formation ◽  
Meconium Aspiration ◽  
Lung Functions

Severe meconium aspiration syndrome (MAS) in newborns is often treated by exogenous surfactant. Because its efficacy is reduced by meconium-induced inflammation, glucocorticoid budesonide was added into surfactant 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 inflammation increased from budesonide-only and surfactant-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 improved the effects of exogenous surfactant in experimental MAS.

scholarly journals N-Acetylcysteine Advancement of Surfactant Therapy in Experimental Meconium Aspiration Syndrome: Possible Mechanisms

2014 ◽  
pp. S629-S642 ◽  
Author(s):  
J. KOPINCOVÁ ◽  
D. MOKRÁ ◽  
P. MIKOLKA ◽  
M. KOLOMAZNÍK ◽  
A. ČALKOVSKÁ
Keyword(s):  
Oxidative Damage ◽  
Therapeutic Effect ◽  
Neutrophil Migration ◽  
Oxygenation Index ◽  
Meconium Aspiration Syndrome ◽  
Surfactant Therapy ◽  
Total Leukocyte Count ◽  
Exogenous Surfactant ◽  
Meconium Aspiration ◽  
Respiratory Parameters

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, 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.

scholarly journals Recombinant Human Superoxide Dismutase and N-Acetylcysteine Addition to Exogenous Surfactant in the Treatment of Meconium Aspiration Syndrome

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 905 ◽  
Author(s):  
Jana Kopincova ◽  
Maros Kolomaznik ◽  
Pavol Mikolka ◽  
Petra Kosutova ◽  
Juliana Topercerova ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Efficiency Index ◽  
Meconium Aspiration Syndrome ◽  
Mitogen Activated Protein Kinase ◽  
Exogenous Surfactant ◽  
Duration Of Treatment ◽  
Pulmonary Tissue ◽  
Meconium Aspiration ◽  
Oxidative Markers ◽  
Mitogen Activated Protein

This study aimed to evaluate the molecular background of N-acetylcysteine (NAC) and recombinant human superoxide dismutase (rhSOD) antioxidant action when combined with exogenous surfactant in the treatment of meconium aspiration syndrome (MAS), considering redox signalling a principal part of cell response to meconium. Young New Zealand rabbits were instilled with meconium suspension (Mec) and treated by surfactant alone (Surf) or surfactant in combination with i.v. NAC (Surf + NAC) or i.t. rhSOD (Surf + SOD), and oxygen-ventilated for 5 h. Dynamic lung-thorax compliance, mean airway pressure, PaO2/FiO2 and ventilation efficiency index were evaluated every hour; post mortem, inflammatory and oxidative markers (advanced oxidation protein products, total antioxidant capacity, hydroxynonenal (HNE), p38 mitogen activated protein kinase, caspase 3, thromboxane, endothelin-1 and secretory phospholipase A2) were assessed in pulmonary tissue homogenates. rhSOD addition to surfactant improved significantly, but transiently, gas exchange and reduced levels of inflammatory and oxidative molecules with higher impact; Surf + NAC had stronger effect only on HNE formation, and duration of treatment efficacy in respiratory parameters. In both antioxidants, it seems that targeting reactive oxygen species may be strong supporting factor in surfactant treatment of MAS due to redox sensitivity of many intracellular pathways triggered by meconium.

PAF potentiates protamine-induced lung edema: role of pulmonary venoconstriction

1990 ◽  
Vol 68 (3) ◽  
pp. 1059-1068 ◽  
Author(s):  
C. R. Chen ◽  
N. F. Voelkel ◽  
S. W. Chang
Keyword(s):  
Body Weight ◽  
Weight Ratio ◽  
Independent Effect ◽  
Lung Edema ◽  
High Dose ◽  
Physiological Salt Solution ◽  
Body Weight Ratio ◽  
Cationic Protein ◽  
Edema Formation

We studied the synergistic interaction between platelet-activating factor (PAF) and protamine sulfate, a cationic protein that causes pulmonary endothelial injury, in isolated rat lungs perfused with a physiological salt solution. A low dose of protamine (50 micrograms/ml) increased pulmonary artery perfusion pressure (Ppa) but did not increase wet lung-to-body weight ratio after 20 min. Pretreatment of the lungs with a noninjurious dose of PAF (1.6 nM) 10 min before protamine markedly potentiated protamine-induced pulmonary vasoconstriction and resulted in severe lung edema and increased lung tissue content of 6-keto-prostaglandin F1 alpha, thromboxane B2, and leukotriene C4. Pulmonary microvascular pressure (Pmv), measured by double occlusion, was markedly increased in lungs given PAF and protamine. These potentiating effects of PAF were blocked by WEB 2086 (10(-5) M), a specific PAF receptor antagonist. Pretreatment of the lungs with a high dose of histamine (10(-4) M) failed to enhance the effect of protamine on Ppa, Pmv, or wet lung-to-body weight ratio. Furthermore, PAF pretreatment enhanced elastase-, but not H2O2-, induced lung edema. To assess the role of hydrostatic pressure in edema formation, we compared lung permeability-surface area products (PS) in papaverine-treated lungs given either protamine alone or PAF + protamine and tested the effect of mechanical elevation of Pmv on protamine-induced lung edema. In the absence of vasoconstriction, PAF did not potentiate protamine-induced increase in lung PS. On the other hand, mechanically raising Pmv in protamine-treated lungs to a level similar to that measured in lungs given PAF + protamine did not result in a comparable degree of lung edema. We conclude that PAF potentiates protamine-induced lung edema predominantly by enhanced pulmonary venoconstriction. However, a pressure-independent effect of PAF on lung vasculature cannot be entirely excluded.

POLYETHYLENE GLYCOL ADDITION DOES NOT IMPROVE EXOGENOUS SURFACTANT FUNCTION IN AN EXPERIMENTAL MODEL OF MECONIUM ASPIRATION SYNDROME

2009 ◽  
Vol 35 (1) ◽  
pp. 76-88 ◽  
Author(s):  
Joao Cesar Lyra ◽  
Renata Suman Mascaretti ◽  
Alexander Roberto Precioso ◽  
Luciana Branco Haddad ◽  
Thais Mauad ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Experimental Model ◽  
Meconium Aspiration Syndrome ◽  
Exogenous Surfactant ◽  
Meconium Aspiration

scholarly journals Anti-Inflammatory Drugs in the Treatment of Meconium Aspiration Syndrome

2011 ◽  
Vol 11 (Supplement-1) ◽  
pp. 15-23
Author(s):  
D. Mokra ◽  
J. Mokry ◽  
A. Calkovska
Keyword(s):  
Lung Parenchyma ◽  
Meconium Aspiration Syndrome ◽  
Experimental Models ◽  
Lung Edema ◽  
Meconium Aspiration ◽  
Pulmonary Vasoconstriction ◽  
Severe Impairment ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Inflammatory Changes

Anti-Inflammatory Drugs in the Treatment of Meconium Aspiration SyndromeMeconium aspiration syndrome (MAS) is a major cause of respiratory distress in both the term and post-term neonates. Obstruction of the airways, dysfunction of pulmonary surfactant, inflammation, lung edema, pulmonary vasoconstriction and bronchoconstriction participate in the pathogenesis of this disorder. Since the inflammatory changes associated with meconium aspiration cause a severe impairment of the lung parenchyma including surfactant and influence the reactivity of both vascular and airway smooth muscle, administration of anti-inflammatory drugs may be of benefit also in the management of MAS. This article reviews effects of various anti-inflammatory drugs used in experimental models of MAS as well as in the treatment of newborns with meconium aspiration.

Vascular permeability and epithelial transport effects on lung edema formation in ischemia and reperfusion

1994 ◽  
Vol 77 (3) ◽  
pp. 1116-1121 ◽  
Author(s):  
P. L. Khimenko ◽  
J. W. Barnard ◽  
T. M. Moore ◽  
P. S. Wilson ◽  
S. T. Ballard ◽  
...  
Keyword(s):  
Weight Ratio ◽  
Dry Weight ◽  
Transport Processes ◽  
Transport Systems ◽  
Lung Edema ◽  
Ischemia And Reperfusion ◽  
Fluid Accumulation ◽  
Edema Formation ◽  
Rat Lungs ◽  
Edema Fluid

To determine the role of various Na+ transport systems in the edema fluid accumulation after ischemia and reperfusion in the lung, we evaluated the effect of amiloride (a Na+ channel blocker), ouabain (a Na(+)-K(+)-adenosinetriphosphatase blocker), and phloridzin (a Na(+)-glucose cotransport blocker) in isolated rat lungs. Ischemia and reperfusion (I/R) significantly increased the edema accumulation, with the wet-to-dry weight ratios increasing to 10.14 +/- 0.58 from 6.03 +/- 0.05 in control lungs (P < 0.04). Amiloride significantly augmented the amount of edema fluid (wet-to-dry weight ratio 12.26 +/- 0.77), and ouabain further increased the amount of edema (wet-to-dry weight ratio 18.58 +/- 1.00). Phloridzin did not significantly affect edema formation associated with I/R. Isoproterenol decreased the amount of edema formation in the presence and absence of amiloride. This occurred because the endothelial permeability as assessed by filtration coefficient was restored to normal values and less edema formed. The present study indicates that Na+ channels and Na(+)-K(+)-adenosinetriphosphatase, components of the active Na+ absorption transport system, are very important in opposing edema fluid accumulation in rat lungs subjected to I/R injury and operate as an edema safety factor. However, if the endothelial damage associated with I/R is allowed to persist, then the transport processes, even if operative, are insufficient to prevent continuous edema accumulation.

Lung to blood passage of different-sized molecules during lung inflammation in the rat

1991 ◽  
Vol 71 (3) ◽  
pp. 1106-1111 ◽  
Author(s):  
H. G. Folkesson ◽  
B. R. Westrom ◽  
S. G. Pierzynowski ◽  
B. W. Karlsson
Keyword(s):  
Protein Content ◽  
Lung Inflammation ◽  
Pulmonary Inflammation ◽  
Intratracheal Instillation ◽  
Dry Weight ◽  
Cell Number ◽  
Total Protein Content ◽  
Lung Edema ◽  
Edema Formation ◽  
Cell Counts

The passage of different-sized marker molecules over the lower respiratory tract into the blood circulation during pulmonary inflammation induced by dextran, endotoxin [i.e., lipopolysaccharide from Escherichia coli (LPS)], or ferritin was assessed in the rat. Bovine immunoglobulin G (BIgG, mol wt = 150,000 Da), bovine serum albumin (BSA, mol wt = 67,000 Da), and the nonapeptide 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, mol wt = 1,067 Da) were used as permeability markers after intratracheal instillation. The pathophysiological indexes of a proceeding lung inflammation were increased total cell number, changed leukocyte proportions and increased total protein content obtained in bronchoalveolar lavage, and lung edema formation shown as an increased lung wet-dry weight difference. Intratracheal instillation of dextran induced a moderate neutrophil invasion into the lungs but had no effect on the passage of the different markers over the lungs (BIgG 1.8 +/- 0.6%, BSA 3.5 +/- 1.2%, dDAVP 26.1 +/- 20.7%) compared with control rats instilled with the markers alone (1.8 +/- 0.4%, 4.1 +/- 1.3%, 20.0 +/- 3.8%, respectively). Endotoxin administration resulted in markedly higher lavage cell counts and lung edema concomitantly with an increased lung passage of the markers (3.2 +/- 0.9%, 22.0 +/- 6.1%, 33.3 +/- 12.0%, respectively; P less than 0.01-P less than 0.001). The highest marker passage was obtained when the inflammation was most severe, i.e., after ferritin administration (17.6 +/- 2.3%, 60.0 +/- 6.7%, 41.6 +/- 6.9%, respectively; P less than 0.001), which resulted in markedly elevated lavage cell numbers and protein content as well as edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Intravenous Dexamethasone Attenuated Inflammation and Influenced Apoptosis of Lung Cells in an Experimental Model of Acute Lung Injury

2016 ◽  
pp. S663-S672 ◽  
Author(s):  
P. KOSUTOVA ◽  
P. MIKOLKA ◽  
S. BALENTOVA ◽  
M. ADAMKOV ◽  
M. KOLOMAZNIK ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Caspase 3 ◽  
Diffuse Alveolar Damage ◽  
Weight Ratio ◽  
Dry Weight ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Edema ◽  
Edema Formation

Acute lung injury (ALI) is characterized by diffuse alveolar damage, inflammation, and transmigration and activation of inflammatory cells. This study evaluated if intravenous dexamethasone can influence lung inflammation and apoptosis in lavage-induced ALI. ALI was induced in rabbits by repetitive saline lung lavage (30 ml/kg, 9±3-times). Animals were divided into 3 groups: ALI without therapy (ALI), ALI treated with dexamethasone i.v. (0.5 mg/kg, Dexamed; ALI+DEX), and healthy non-ventilated controls (Control). After following 5 h of ventilation, ALI animals were overdosed by anesthetics. Total and differential counts of cells in bronchoalveolar lavage fluid (BAL) were estimated. Lung edema was expressed as wet/dry weight ratio. Concentrations of IL-1ß, IL-8, esRAGE, S1PR3 in the lung were analyzed by ELISA methods. In right lung, apoptotic cells were evaluated by TUNEL assay and caspase-3 immunohistochemically. Dexamethasone showed a trend to improve lung functions and histopathological changes, reduced leak of neutrophils (P<0.001) into the lung, decreased concentrations of pro-inflammatory IL-1β (P<0.05) and marker of lung injury esRAGE (P<0.05), lung edema formation (P<0.05), and lung apoptotic index (P<0.01), but increased immunoreactivity of caspase-3 in the lung (P<0.001). Considering the action of dexamethasone on respiratory parameters and lung injury, the results indicate potential of this therapy in ALI.

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