scholarly journals Effects of Nitric Oxide Donor on the Lung Functions in a Saline Lavage-Induced Model of ARDS

2019 ◽  
pp. S265-S273 ◽  
Author(s):  
P. KOSUTOVA ◽  
P. MIKOLKA ◽  
S. BALENTOVA ◽  
M. ADAMKOV ◽  
D. MOKRA
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Cell Count ◽  
Nitric Oxide Donor ◽  
Control Group ◽  
Lung Edema ◽  
Edema Formation ◽  
Respiratory Parameters ◽  
Lung Functions ◽  
Saline Lavage

Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia, neutrophil-mediated inflammation, and lung edema formation. Whereas lung damage might be alleviated by nitric oxide (NO), goal of this study was to evaluate if intratracheal NO donor S-nitroso-N-acetylpenicillamine (SNAP) can positively influence the lung functions in experimental model of ARDS. New Zealand rabbits with respiratory failure induced by saline lavage (30 ml/kg, 9±3 times) were divided into: ARDS group without therapy, ARDS group treated with SNAP (7 mg/kg i.t.), and healthy Control group. During 5 h of ventilation, respiratory parameters (blood gases, ventilatory pressures) were estimated. After anesthetics overdosing, left lung was saline-lavaged and cell count, cell viability and protein content in bronchoalveolar lavage fluid (BALF) were measured. Right lung tissue was used for estimation of wet/dry weight ratio, concentration of NO metabolites, and histomorphological investigation. Repetitive lung lavage induced lung injury, worsened gas exchange, and damaged alveolar-capillary membrane. Administration of SNAP reduced cell count in BALF, lung edema formation, NO metabolites, and histopathological signs of injury, and improved respiratory parameters. Treatment with intratracheal SNAP alleviated lung injury and edema and improved lung functions in a saline-lavaged model of ARDS suggesting a potential of NO donors also for patients with ARDS.

Superoxide dismutase potentiates platelet-activating factor-induced injury in perfused lung

1994 ◽  
Vol 266 (3) ◽  
pp. L246-L254 ◽  
Author(s):  
Y. C. Huang ◽  
E. S. Nozik ◽  
C. A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Superoxide Dismutase ◽  
Lung Injury ◽  
Platelet Activating Factor ◽  
Anion Channel ◽  
Lung Edema ◽  
Rabbit Lung ◽  
Edema Formation ◽  
Nitric Oxide Synthase Inhibitor

Platelet-activating factor (PAF) causes pulmonary hypertension and lung edema in animals and isolated perfused lungs by poorly understood mechanisms. Because oxidative mechanisms have been implicated in PAF-mediated cellular injury, we tested the hypothesis that superoxide anion (O2-.) contributes to PAF-induced lung injury by determining whether superoxide dismutase (SOD) could prevent the lung injury. Isolated rabbit lungs were perfused with PAF (100 nM) at a dose that caused transient hypertension and mild edema. Lungs pretreated with Cu,Zn SOD (100 U/ml) for 10 min developed persistent pulmonary hypertension and more lung edema formation in response to PAF. Enhanced responses to PAF also were observed in lungs perfused with 200 U/ml Cu,Zn SOD, but not with 10 or 40 U/ml Cu,Zn SOD. The higher doses of SOD also decreased thromboxane B2 levels in the perfusate. Potentiation of the PAF effect by Cu,Zn SOD was eliminated if the enzyme was inactivated or if the lung was treated with an anion channel blocker. The augmented PAF response in the presence of SOD was not altered by catalase (200 U/ml) or by nitric oxide synthase inhibitor. The data suggest that excessive Cu,Zn SOD enzyme activity potentiates PAF-induced injury in perfused rabbit lung presumably by overscavenging extracellular O2.- generated from intercellular sources. The augmented responses to PAF are not directly attributable to increased hydrogen peroxide, nitric oxide-related products, or thromboxane A2 production. These results suggest the new hypothesis that a balance between O2-. production and its metabolism determines vascular and endothelial responses to PAF.

scholarly journals Effects of Roflumilast, a Phosphodiesterase-4 Inhibitor, on the Lung Functions in a Saline Lavage-Induced Model of Acute Lung Injury

2017 ◽  
pp. S237-S245 ◽  
Author(s):  
P. KOSUTOVA ◽  
P. MIKOLKA ◽  
M. KOLOMAZNIK ◽  
S. REZAKOVA ◽  
A. CALKOVSKA ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Lung Compliance ◽  
Pde4 Inhibitor ◽  
Lung Edema ◽  
Lung Weight ◽  
Edema Formation ◽  
Phosphodiesterase 4 ◽  
Respiratory Parameters

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.

scholarly journals Sodium Nitrite Mitigates Ventilator-induced Lung Injury in Rats

2012 ◽  
Vol 117 (3) ◽  
pp. 592-601 ◽  
Author(s):  
Philipp A. Pickerodt ◽  
Michael J. Emery ◽  
Rachel Zarndt ◽  
William Martin ◽  
Roland C. E. Francis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Catalytic Reduction ◽  
Lung Edema ◽  
Xanthine Oxidoreductase ◽  
Positive End Expiratory Pressure ◽  
Edema Formation ◽  
Ventilator Induced Lung Injury ◽  
Volume Ventilation ◽  
Oxide Synthase

Background Nitrite (NO2) is a physiologic source of nitric oxide and protects against ischemia-reperfusion injuries. We hypothesized that nitrite would be protective in a rat model of ventilator-induced lung injury and sought to determine if nitrite protection is mediated by enzymic catalytic reduction to nitric oxide. Methods Rats were anesthetized and mechanically ventilated. Group 1 had low tidal volume ventilation (LVT) (6 ml/kg and 2 cm H2O positive end-expiratory pressure; n=10); group 2 had high tidal volume ventilation (HVT) (2 h of 35 cm H2O inspiratory peak pressure and 0 cm H2O positive end-expiratory pressure; n=14); groups 3-5: HVT with sodium nitrite (NaNO2) pretreatment (0.25, 2.5, 25 μmol/kg IV; n=6-8); group 6: HVT+NaNO2+nitric oxide scavenger 2-(4-carboxyphenyl)-4,5dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3oxide(n=6); group 7: HVT+NaNO2+nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (n=7); and group 8: HVT+NaNO2+xanthine oxidoreductase inhibitor allopurinol (n=6). Injury assessment included physiologic measurements (gas exchange, lung compliance, lung edema formation, vascular perfusion pressures) with histologic and biochemical correlates of lung injury and protection. Results Injurious ventilation caused statistically significant injury in untreated animals. NaNO2 pretreatment mitigated the gas exchange deterioration, lung edema formation, and histologic injury with maximal protection at 2.5 μmol/kg. Decreasing nitric oxide bioavailability by nitric oxide scavenging, nitric oxide synthase inhibition, or xanthine oxidoreductase inhibition abolished the protection by NaNO2. Conclusions Nitrite confers protection against ventilator-induced lung injury in rats. Catalytic reduction to nitric oxide and mitigation of ventilator-induced lung injury is dependent on both xanthine oxidoreductase and nitric oxide synthases.

scholarly journals Effects of Conventional Mechanical Ventilation Performed by Two Neonatal Ventilators on the Lung Functions of Rabbits with Meconium-Induced Acute Lung Injury

2016 ◽  
Vol 16 (3) ◽  
pp. 5-13
Author(s):  
D Mokra ◽  
P Mikolka ◽  
P Kosutova ◽  
M Kolomaznik ◽  
M Jurcek ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Small Volume ◽  
Left Lung ◽  
Conventional Mechanical Ventilation ◽  
Lung Edema ◽  
Edema Formation ◽  
Lung Functions

AbstractSevere meconium aspiration syndrome (MAS) in the neonates often requires a ventilatory support. As a method of choice, a conventional mechanical ventilation with small tidal volumes (VT<6 ml/kg) and appropriate ventilatory pressures is used. The purpose of this study was to assess the short-term effects of the small-volume CMV performed by two neonatal ventilators: Aura V (Chirana Stara Tura a.s., Slovakia) and SLE5000 (SLE Ltd., UK) on the lung functions of rabbits with experimentally-induced MAS and to estimate whether the newly developed neonatal version of the ventilator Aura V is suitable for ventilation of the animals with MAS.In the young rabbits, a model of MAS was induced by an intratracheal instillation of a suspension of neonatal meconium (4 ml/kg, 25 mg/ml). After creating the model of MAS, the animals were ventilated with small-volume CMV (frequency 50/min, VT<6 ml/kg, inspiration time 50 %, fraction of inspired oxygen 1.0, positive end-expiratory pressure 0.5 kPa, mean airway pressure 1.1 kPa) performed by ventilator Aura V (Aura group, n=7) or ventilator SLE5000 (SLE group, n=7) for additional 4 hours. One group of animals served as healthy non-ventilated controls (n=6). Blood gases, oxygenation indexes, ventilatory pressures, lung compliance, oxygen saturation and total and differential white blood cell (WBC) count were regularly determined. After euthanizing the animals, a left lung was saline-lavaged and total and differential counts of cells in the bronchoalveolar lavage (BAL) fluid were determined. A right lung was used for estimation of lung edema formation (expressed as a wet/dry weight ratio) and for analysis of concentrations of pro-inflammatory cytokines (IL-1β, IL-8, TNF). The cytokines were measured also in the blood plasma taken at the end of experiment.Meconium instillation seriously worsened the gas exchange and induced inflammation and lung edema formation. In the Aura group, slightly lower concentrations of cytokines were found and better gas exchange early after creating the MAS model was observed. However, there were no significant differences in the respiratory parameters between the ventilated groups at the end of experiment (P>0.05).Concluding, the newly developed neonatal version of the ventilator Aura V was found to be fully comparable to widely used neonatal ventilator SLE5000. Results provided by Aura V in CMV ventilation of rabbits with meconium-induced acute lung injury suggest its great potential also for future clinical use, i.e. for ventilation of the neonates with MAS.

Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury

1997 ◽  
Vol 273 (3) ◽  
pp. L504-L512 ◽  
Author(s):  
Y. C. Huang ◽  
P. W. Fisher ◽  
E. Nozik-Grayck ◽  
C. A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Average Rate ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
No Production ◽  
Protective Effects ◽  
Lung Weight ◽  
Edema Formation ◽  
No Donors

Because both the biosynthesis of nitric oxide (NO.) and its metabolic fate are related to molecular O2, we hypothesized that hypoxia would alter the effects of NO. during ischemia-reperfusion (IR) in the lung. In this study, buffer-perfused lungs from rabbits underwent either normoxic IR (AI), in which lungs were ventilated with 21% O2 during ischemia and reperfusion, or hypoxic IR (NI), in which lungs were ventilated with 95% N2 during ischemia followed by reoxygenation with 21% O2. Lung weight gain (WG) and pulmonary artery pressure (Ppa) were monitored continuously, and microvascular pressure (Pmv) was measured after reperfusion to calculate pulmonary vascular resistance. We found that both AI and NI produced acute lung injury, as shown by increased WG and Ppa during reperfusion. In AI, where perfusate PO2 was > 100 mmHg, the administration of the NO. synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before ischemia worsened WG and Ppa. Pmv also increased, suggesting a hydrostatic mechanism involved in edema formation. The effects of L-NAME could be attenuated by giving L-arginine and exogenous NO. donors before ischemia or before reperfusion. Partial protection was also provided by superoxide dismutase. In contrast, lung injury in NI at perfusate PO2 of 25-30 mmHg was attenuated by L-NAME; this effect could be reversed by L-arginine. Exogenous NO. donors given either before ischemia or before reperfusion, however, did not increase lung injury. NO. production was measured by quantifying the total nitrogen oxides (NOx) accumulating in the perfusate. The average rate of NOx accumulation was greater in AI than in NI. We conclude that hypoxia prevented the protective effects of NO on AI lung injury. The effects of hypoxia may be related to lower NO. production relative to oxidant stress during IR and/or altered metabolic fates of NO.-mediated production of peroxynitrite by hypoxic ischemia.

Inhaled nitric oxide reduces lung edema during fluid resuscitation in ovine acute lung injury

2003 ◽  
Vol 29 (10) ◽  
pp. 1790-1797 ◽  
Author(s):  
Henning D. Stubbe ◽  
Martin Westphal ◽  
Hugo Van Aken ◽  
Christoph Hucklenbruch ◽  
Stefan Lauer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Fluid Resuscitation ◽  
Inhaled Nitric Oxide ◽  
Lung Edema

scholarly journals Acute lung injury inhibition by juglone in LPS induced sepsis mouse model involves Sirt1 activation

2020 ◽  
Vol 19 (5) ◽  
pp. 1001-1007
Author(s):  
Qiong Hu ◽  
Chunai Yang ◽  
Fenshuang Zheng ◽  
Hongdan Duan ◽  
Yangshan Fu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Alveolar Epithelial Cells ◽  
Control Group ◽  
Western Blot Assay ◽  
Edema Formation ◽  
Sirt1 Expression ◽  
Treatment Groups

Purpose: To investigate the effect of juglone on LPS induced lung injury in a mouse model and in TC 1cell line.Methods: Edema formation in lungs were measured by determination of lung wet/dry weight. Expressions of various proteins were assessed by western blot assay, while Sirt1 level was assessed using immunohistochemistry. Mice were randomly assigned to nine groups of 10 mice each: normal control, untreated and seven juglone treatment groups. Acute lung injury was induced in mice by injecting LPS (10 mg/kg) via intraperitoneal route (ip). The treatment groups were given 10, 20, 30, 40, 50, 60 and 100 μM of juglone, ip, respectively.Results: The levels of MMP-9, IL-6, IL-1β and iNOS were significantly higher in acute lung injury induced mice compared than the control group (p < 0.05). Treatment of the mice with juglone significantly decreased LPS-induced up-regulation of inflammatory cytokines in a dose-dependentmanner. The production of inflammatory cytokines was almost completely inhibited in the mice treated with 100 mg/kg dose of juglone, while treatment of the LPS-stimulated TC 1 cells with juglone upregulated the expression of Sirt1 mRNA. Down-regulation of Sirt1 expression by siRNA inhibited the effect of juglone on LPS-induced increase in inflammatory cytokine production.Conclusion: Juglone prevents lung injury in mice via up-regulation of Sirt1 expression. Therefore, juglone might be useful for the development of a treatment strategy for lung injury. Keywords: Inflammatory, Sirtuin, Edema, Cytokines, Lung injury, TC 1 lung alveolar epithelial cells, Sirt1

Aerosolized Soluble Nitric Oxide Donor Improves Oxygenation and Pulmonary Hypertension in Acute Lung Injury

1998 ◽  
Vol 158 (5) ◽  
pp. 1536-1542 ◽  
Author(s):  
BRIAN R. JACOBS ◽  
RICHARD J. BRILLI ◽  
EDGAR T. BALLARD ◽  
DANIEL J. PASSERINI ◽  
DANIEL J. SMITH
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nitric Oxide Donor

Beneficial Effects of Supplemental Nitric Oxide Donor Given during Reperfusion Period in Reperfusion-Induced Lung Injury

2006 ◽  
Vol 54 (7) ◽  
pp. 477-483 ◽  
Author(s):  
H. Esme ◽  
H. Fidan ◽  
O. Solak ◽  
F. Dilek ◽  
R. Demirel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Nitric Oxide Donor ◽  
Beneficial Effects ◽  
Reperfusion Period
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