dinoprost and Respiratory-Distress-Syndrome

In the middle of the nineties a new, non-invasive method for investigation of the lung aroused the interest of many researchers: the exhaled breath condensate. It shows the extent of the interest that in the last five years more than 80 original articles have been published in this theme. Many substances are found in the expired breath which are detectable in the liquid that we obtain by cooling (= condensing) the exhaled breath. The advantages of this method are that it is non-invasive, convenient, it could be performed with mechanically ventilated patients as well as with children. The most studied substance is the hydrogen-peroxide, which is the marker of oxidative stress, and its level in condensate is elevated in numerous inflammatory diseases. 8-isoprostane was also studied a lot, which is another marker of oxidative stress. Numerous substances could be even measured in condensate, so the decay-product of nitric-oxide (nitrite, nitrate, nitrotyrosine), further nitrosothiol, adenosine, ammonia, different ions, leukotrienes, cytokines; recently even other feature of condensate is examined, such as its pH. The different mediators could help us to know better the diseases, support the diagnosis, follow the treatment or the disease. In this study the authors attempt to present the most important knowledge till now.

Topics: Asthma; Biomarkers; Breath Tests; Bronchiectasis; Cystic Fibrosis; Dinoprost; F2-Isoprostanes; Humans; Hydrogen Peroxide; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Respiratory Tract Diseases; Smoking

To observe the clinical significance of nitric oxide (NO) and 8-isoprostane (8-isoPG) changes in exhaled breath condensate ( EBC) of acute respiratory distress syndrome (ARDS) patients after treated by Qingfei Decoction (QD).. Totally 48 ARDS patients receiving mechanical ventilation were equally assigned to the QD treatment group and the control group by random digit table. EBC specimens were collected by modified Ecoscreen breath condensate collector (German JAEGER Company) on the first day and the fifth day after confirmed diagnosis of ARDS. Concentrations of NO and 8-isoPG in EBC were measured by ELISA. The oxygenation index and APACHE II scores were recorded at the same time.. (1) The fatality rate in the QD treatment group was lower than that in the control group (8.3% vs 37.5%, P < 0.05). (2) After treatment NO and 8-isoPG concentrations in EBC were lower in the QD treatment group (34.49 ± 5.67 µmol/L, 30.09 ± 7.89 ng/L) than in the control group (39.78 ± 9.27 µmol/L, 35.65 ± 8.90 ng/L; P < 0.05). (3) After treatment improved oxygenation index value was higher in the QD treatment group than in the control group (120.88 ± 35.16 vs 101.50 ± 37.70, P < 0.05). After treatment APACHEII scores was lower in the QD treatment group than in the control group (6.21 ± 3.51 vs 10. 26 ± 4.33, P < 0.05).. Treatment of ARDS patients by QD was favorable in controlling inflammation, alleviating lung injury, and improving clinical efficacy.

Topics: Breath Tests; Dinoprost; Drugs, Chinese Herbal; Humans; Inflammation; Nitric Oxide; Respiration, Artificial; Respiratory Distress Syndrome

The benefits of beta-adrenergic stimulation have been described in acute lung injury (ALI), but there is still no evidence of its anti-inflammatory effect in these patients. Biomarkers in exhaled breath condensate (EBC) were used to study the effects of salbutamol on lung inflammation in mechanically ventilated patients with ALI.. EBC was collected before and 30 minutes after administration of inhaled salbutamol (800 microg). The following parameters were measured in the samples: volume obtained, conductivity, pH after helium deaeration, and concentration of nitrites, nitrates and 8-isoprostane. The leukotriene B4 concentration was measured after sample lyophilization and reconstitution. Results are expressed as the median (interquartile range).. EBC was obtained from six ALI patients, with a median age of 56 (46 to 76) years. At the time of EBC collection, the Lung Injury Score was 3 (2.3 to 3.1) and the PaO2/FIO2 ratio was 133 (96 to 211) mmHg. A significant increase in deaerated EBC pH was observed after salbutamol administration (7.66 (7.58 to 7.75) versus 7.83 (7.67 to 7.91), P = 0.028). Trends toward decreased nitrosative species (18.81 (13.33 to 49.44) microM versus 21.21 (8.07 to 29.83) microM, P = 0.173) and decreased 8-isoprostane concentration (11.64 (7.17 to 17.13) pg/ml versus 6.55 (4.03 to 9.99) pg/ml, P = 0.068) were detected. No changes in leukotriene B4 concentration were found (1.58 (0.47 to 3.57) pg/ml versus 2.06 (1.01 to 3.01) pg/ml, P = 0.753).. EBC analysis is a noninvasive technique that can be used to monitor ventilated patients. In EBC from a small cohort of patients with ALI, inhaled salbutamol significantly decreased airspace acidosis, a marker of inflammation, and was associated with a trend toward decreased markers of nitrosative and oxidative stress.

Topics: Adrenergic beta-Agonists; Aged; Albuterol; Biomarkers; Breath Tests; Dinoprost; Exhalation; Female; Humans; Hydrogen-Ion Concentration; Leukotriene B4; Male; Metered Dose Inhalers; Middle Aged; Nitrates; Nitrites; Prospective Studies; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Distress Syndrome; Severity of Illness Index

Pulmonary oxidant stress is an important pathophysiologic feature of acute lung injury. It is unclear whether nitric oxide contributes to this oxidant stress. Thus, we examined the role of inducible nitric oxide synthase (iNOS) in pulmonary oxidant stress in murine sepsis and the differential contribution of different cellular sources of iNOS.. Randomized, controlled animal study.. Research laboratory of an academic institution.. Male iNOS+/+, iNOS-/- C57Bl/6 mice, and bone-marrow transplanted iNOS chimeric mice: +to- (wild-type iNOS+/+ donor bone-marrow transplanted into iNOS-/- recipient mice) and the reciprocal -to+ chimeras.. Animals were randomized to sepsis (n = 264), induced by cecal ligation and perforation, vs. naive groups (n = 138).. In septic iNOS-/- vs. wild-type iNOS+/+ mice, sepsis-induced pulmonary oxidant stress (33 +/- 11 [mean +/- sem] vs. 365 +/- 48 pg 8-isoprostane/mg protein, p < .01) and nitrosative stress (0.0 +/- 0.0 vs. 0.9 +/- 0.4 micromol 3-nitrotyrosine/mmol para-tyrosine, p < .05) were abolished, despite similar septic increases in pulmonary myeloperoxidase activity in both (86 +/- 20 vs. 83 +/- 12 mU/mg protein, p = .78). In +to- iNOS chimeric mice (iNOS localized only to donor bone-marrow-derived inflammatory cells), cecal ligation and perforation resulted in significant pulmonary oxidant stress (368 +/- 81 pg 8-isoprostane/mg protein) and nitrosative stress (0.6 +/- 0.2 micromol 3-nitrotyrosine/mmol para-tyrosine), similar in degree to septic wild-type mice. In contrast, pulmonary oxidant and nitrosative stresses were absent in septic -to+ iNOS chimeras (iNOS localized only to recipient parenchymal cells), similar to iNOS-/- mice.. In murine sepsis-induced acute lung injury, pulmonary oxidant stress is completely iNOS dependent and is associated with tyrosine nitration. Moreover, pulmonary oxidant stress and nitrosative stress were uniquely dependent on the presence of iNOS in inflammatory cells (e.g., macrophages and neutrophils), with no apparent contribution of iNOS in pulmonary parenchymal cells. iNOS inhibition targeted specifically to inflammatory cells may be an effective therapeutic approach in sepsis and acute lung injury.

Topics: Analysis of Variance; Animals; Bone Marrow Transplantation; Chimera; Dinoprost; Lung; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Random Allocation; Respiratory Distress Syndrome; Sepsis; Tyrosine

Although inhaled nitric oxide transiently improves oxygenation in patients with acute lung injury, it has not affected clinical outcomes. As well, the effects of inhaled nitric oxide on the pathophysiologic features of acute lung injury have not been well defined. Therefore, we assessed the effects of inhaled nitric oxide on the degree of pulmonary inflammation and injury in a mouse model of sepsis-induced acute lung injury.. Randomized, controlled animal study.. Research laboratory of an academic institution.. Male C57Bl/6 mice.. Sepsis was induced by cecal ligation and perforation. At the time of surgery, septic and naïve mice were randomized to exposure to either 40 ppm inhaled nitric oxide or room air for 24 hrs before they were killed.. Sepsis-induced acute lung injury was characterized by increased pulmonary myeloperoxidase (68 +/- 13 vs. 13 +/- 3 mU/mg protein in naïve mice, p <.01), pulmonary 8-isoprostane content (627 +/- 51 vs. 88 +/- 20 pg/mg protein in naïve mice, p <.01), and protein in bronchoalveolar lavage fluid (p <.05). Inhaled nitric oxide exposure in septic mice completely abrogated the septic increases in myeloperoxidase activity (p <.05) and pulmonary 8-isoprostane content (p <.05) but had no effect on bronchoalveolar lavage protein. The induction of sepsis also was associated with an increase in pulmonary inducible NO synthase activity (2.8 +/- 0.5 vs. 0.4 +/- 0.1 pmol small middle dotmin-1 small middle dotmg-1 protein in naïve mice, p <.05), and inhaled nitric oxide attenuated this increase in pulmonary inducible NO synthase activity (p <.05).. Exposure to inhaled nitric oxide early in the course of sepsis-induced acute lung injury is associated with reduced pulmonary leukocyte infiltration and less oxidative injury. Decreased lung inflammation and injury with inhaled nitric oxide is associated with decreased pulmonary inducible NO synthase activity. Therefore, inhaled NO may have greater clinical benefit if administered earlier in the natural history of acute lung injury in patients.

Topics: Administration, Inhalation; Animals; Dinoprost; F2-Isoprostanes; Lung; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Nitric Oxide Synthase; Peroxidase; Random Allocation; Respiratory Distress Syndrome; Systemic Inflammatory Response Syndrome

Oxidant stress is a purported mechanism of tissue damage in patients with ARDS and acute lung injury (ALI). Isoprostanes, prostanoid compounds primarily formed nonenzymatically via lipid peroxidation, are precise markers of in vivo oxidant stress. Plasma levels of metabolites of 8-iso-prostaglandin-F2alpha (8-iso-PGF2alpha) correlate with outcome in patients with ARDS.. To examine exhaled breath condensate levels of 8-iso-PGF2alpha as a noninvasive quantification of pulmonary oxidant stress in patients with, or at risk for, ARDS/ALI.. Breath condensate was collected from 22 patients with, or at risk for, ARDS/ALI by placing Tygon tubing submerged in an ice bath in line with the expiratory limb of the ventilator circuit. Ten patients without lung disease, who were intubated while undergoing minor surgical procedures, served as control subjects. Between 1 and 3 mL of condensate was collected over a 30- to 60-min period, then immediately frozen and stored at -70 degrees C until analysis. The 8-iso-PGF2alpha was purified and derivatized, then quantified by stable isotope dilution in conjunction with gas chromatography/mass spectrometry.. The mean level of exhaled 8-iso-PGF2alpha in the patients with ALI/ARDS, 87+/-28 pg/mL, was significantly higher than the mean in the normal group, 7+/-4 pg/mL (p = 0.007). The 8-iso-PGF2alpha levels were greater than two standard deviations above the mean of the normal group in 12 of 22 patients with or at risk for ARDS/ALI.. These results provide further evidence that lipid peroxidation does occur in patients with ARDS/ALI. The measurement of exhaled isoprostanes provides a novel, noninvasive method to quantify oxidant stress in such patients.

Topics: Breath Tests; Dinoprost; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Respiratory Distress Syndrome; Vasoconstrictor Agents

We hypothesized that endotoxin injection in rats would stimulate in vivo nuclear factor-kappa B (NF-kappa B) activation in lung tissue and that antioxidant treatment before endotoxin injection would attenuate endotoxin-induced NF-kappa B activation, chemokine gene expression, and neutrophilic lung inflammation. We studied NF-kappa B activation in rat lung tissue following a single i.p. injection of endotoxin (6 mg/kg). After in vivo endotoxin treatment, lung NF-kappa B activation peaked at 2 h and temporally correlated with the expression of cytokine-induced neutrophil chemoattractant mRNA in lung tissue. Treatment with the antioxidant N-acetylcysteine (NAC) 1 h before endotoxin resulted in decreased lung NF-kappa B activation in a dose-dependent manner (from 200-1000 mg/kg) and diminished cytokine-induced neutrophil chemoattractant mRNA expression in lung tissue. Treatment with NAC significantly suppressed endotoxin-induced neutrophilic alveolitis. The average total lung lavage neutrophil count was 5.5 x 10(6) with endotoxin treatment vs 0.9 x 10(6) with NAC treatment before endotoxin. The NF-kappa B pathway represents an attractive therapeutic target for strategies to control neutrophilic inflammation and lung injury.

Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Base Sequence; Chemokines, CXC; Chemotactic Factors; Chemotaxis, Leukocyte; Dinoprost; Disease Models, Animal; Drug Evaluation, Preclinical; Endotoxins; F2-Isoprostanes; Gene Expression Regulation; Glutathione; Growth Substances; Inflammation; Intercellular Signaling Peptides and Proteins; Leukocyte Count; Lung; Lung Diseases; Male; Molecular Sequence Data; Neutrophils; NF-kappa B; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome; RNA, Messenger; Sepsis

Inhalation of nitric oxide (NO) selectively dilates pulmonary vessels in well-ventilated regions. Prostaglandin F2 alpha (PGF2 alpha) is a vasoconstrictor and is reported to enhance hypoxic pulmonary vasoconstriction. The objective of this study was to examine whether the combination of intravenous PGF2 alpha and inhaled NO in ARDS lungs has a beneficial effect on oxygenation.. We investigated the effect of intravenous PGF2 alpha infusion (0.05-10.0 micrograms/kg per min) with and without NO inhalation (60 ppm) on the hemodynamics and gas exchange in an ovine ARDS model, examining the pulmonary artery pressure versus the flow plot by varying cardiac output.. After lung lavage, NO inhalation reduced the mean pulmonary arterial pressure (MPAP) by decreasing the zero-flow pressure intercept from 10.6 +/- 3.8 (mean +/- SD) to 8.5 +/- 3.8 mmHg (p < 0.05) with no significant change in slope. NO inhalation improved PaO2 from 56 +/- 12 to 84 +/- 38 mmHg (p < 0.005) and reduced pulmonary shunt from 65 +/- 5 to 53 +/- 8% (Qs/Qt) (p < 0.001). The dose-dependent effects of PGF2 alpha infusion were: (1) increased MPAP attributed to an increased slope in pulmonary artery pressure-flow plot; (2) decreased cardiac index; (3) decreased Qs/Qt with unchanged PaO2. The dose-dependent decrease in Qs/Qt after PGF2 alpha infusion was attributed to the decreased cardiac output.. It is suggested that inhalation of NO reduced the critical vascular pressure near alveoli without affecting upstream vessels, while infused PGF2 alpha constricted the larger upstream pulmonary artery vessels without appreciably affecting the critical pressure. Inhalation of NO into well-ventilated lung areas shifted perfusion to well-oxygenated areas, and there was no supplemental shift in blood flow by adding an infusion of PGF2 alpha.

Topics: Administration, Inhalation; Animals; Blood Gas Analysis; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Infusions, Intravenous; Nitric Oxide; Pulmonary Circulation; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Sheep