Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Increase in exhaled nitric oxide and protective role of the nitric oxide system in experimental pulmonary embolism.

ABSTRACT: BACKGROUND AND PURPOSE: Pulmonary embolism (PE) represents a real diagnostic challenge. PE is associated with pulmonary hypertension due to pulmonary vascular obstruction and vasoconstriction. We recently reported that pulmonary gas embolism transiently increases exhaled nitric oxide (FENO), but it is not known whether solid emboli may alter FENO, and whether an intact endogenous NO synthesis has a beneficial effect in experimental solid pulmonary embolism. EXPERIMENTAL APPROACH: We used anaesthetised and ventilated rabbits in these experiments. To mimic PE, a single intravenous infusion of homogenized autologous skeletal muscle tissue (MPE) was given to rabbits with intact NO production (MPE of 60, 15, or 7.5 mg kg(-1); group 1) and to another group (group 2) with inhibited NO synthesis (L-NAME 30 mg kg(-1); MPE of 7.5, 15 or 30 mg kg(-1)). KEY RESULTS: In group 1, after MPE, FENO increased rapidly and dose-dependently and FENO was still significantly elevated after 60 min with the two highest emboli doses. All these animals survived more than 60 min after embolization. In group 2, MPE of 7.5, 15 and 30 mg kg(-1), in combination with NO synthesis inhibition, resulted in 67%, 50% and 25% survival at 60 min respectively, representing a statistically significant decrease in survival. Cardiovascular and blood-gas changes after MPE were intensified by pre-treatment with NO synthesis inhibitor. CONCLUSIONS AND IMPLICATIONS: We conclude that solid PE causes a sustained, dose-dependent increase in FENO, giving FENO a diagnostic potential in PE. Furthermore, intact NO production appears critical for tolerance to acute PE.

SUBMITTER: Nilsson KF

PROVIDER: S-EPMC2189723 | biostudies-other | 2007 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema.

Project description:The purpose of this study is to comprehensively elucidate the role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema using cap analysis of gene expression (CAGE) sequencing.

2021-01-18 | GSE164521 | GEO

Role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema.

Project description:Role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema.

| PRJNA691047 | ENA

Effect of Inhaled ?2-Agonist on Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease.

Project description:The fractional exhaled nitric oxide measured at an expiratory flow of 50mL/s (FENO50) is a marker of airway inflammation, and high levels are associated with greater response to steroid treatment. In asthma, FENO50 increases with bronchodilation and decreases with bronchoconstriction, the latter potentially causing an underestimate of the degree of airway inflammation when asthma worsens. It is unknown whether the same effect occurs in chronic obstructive lung disease (COPD). Likewise, it is not known whether changes in airway calibre in COPD patients alter flow-independent parameters describing pulmonary nitric oxide exchange, such as the maximal flux of nitric oxide (NO) from the proximal airway compartment (J'awNO) and the distal airway/alveolar concentration of NO (CANO). We recruited 24 patients with COPD and performed FENO analysis at multiple expiratory flows before and after treatment with inhaled ?2-agonist bronchodilator therapy. For the 21 patients analysed, FENO50 rose from 17.1 (1.4) ppb (geometric mean (geometric SD)) at baseline, to 19.3 (1.3) ppb after bronchodilator therapy, an increase of 2.2 ppb (95% CI, 0.7-3.6; P = 0.005). There were non-significant changes in flow-independent NO parameters. The change in FENO50 correlated positively with the change in J'awNO (rs = 0.67, P < 0.001; rs = 0.62, P = 0.002 before and after correction for axial back-diffusion respectively) following bronchodilation. Inhaled bronchodilator therapy can increase exhaled nitric oxide measurements in COPD. The standardisation of inhaled bronchodilator therapy before FENO analysis in COPD patients should therefore be considered in both research and clinical settings.

| S-EPMC4892672 | biostudies-literature

Treatment of chronic obstructive pulmonary disease in patients with different fractional exhaled nitric oxide levels.

Project description:Some patients with chronic obstructive pulmonary disease (COPD) have eosinophilic inflammation which may be evaluated via the measurement of fractional exhaled nitric oxide (FeNO) like asthma. The aim of this prospective study was to assess whether FeNO levels can be used to identify patients with COPD with eosinophilic inflammation who may respond to inhaled corticosteroid (ICS) therapy.This study included patients (N?=?112) with COPD (age >18 years) who were divided into 4 groups depending upon whether they had high (?25 parts per billion [ppb]) or low (<25 ppb) pretreatment (baseline) FeNO and if they were treated with either ICS plus long-acting ?-agonist (ICS?+?LABA) or a long-acting muscarinic antagonist (LAMA). The 4 groups were: high FeNO/ICS?+?LABA, high FeNO/LAMA, low FeNO/ICS?+?LABA, and low FeNO/LAMA. Outcomes assessed included FeNO, COPD assessment test (CAT), and pulmonary function.The high FeNO/ICS?+?LABA group had the greatest reduction from baseline in FeNO levels (-25.80 ppb?±?27.14) compared with the high FeNO/LAMA, low FeNO/ICS?+?LABA, and low FeNO/LAMA groups (range, -4.45 to 1.31 ppb; P?<?.001). The high FeNO/ICS?+?LABA group also showed the greatest improvement in CAT (-7.20), which was statistically larger than the low FeNO/ICS?+?LABA and low FeNO/LAMA groups (-1.72 and -2.03, respectively). No difference in pulmonary function following treatment was observed across the 4 groups.This study found that patients with high FeNO showed the greatest reduction in FeNO and improvement in CAT with ICS?+?LABA therapy, supporting the use of FeNO to identify patients who would benefit from ICS use.

| S-EPMC6392665 | biostudies-literature

Inhaled nitric oxide to treat intermediate risk pulmonary embolism: A multicenter randomized controlled trial.

Project description:OBJECTIVE:To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. METHODS:This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50?parts per million nitrogen (placebo) or oxygen plus 50?ppm NO for 24?h. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14?pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration <90?pg/mL and a Borg dyspnea score???2. The sample size of N?=?76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha?=?5%. RESULTS:We randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24?h, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P?=?0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P?=?0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24?h (P?=?0.010, Cochrane's Q test). CONCLUSIONS:In patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography. CLINICAL TRIAL REGISTRATION:NCT01939301.

| S-EPMC7047892 | biostudies-literature

Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial.

Project description:BackgroundThe study hypothesis is that administration of inhaled nitric oxide (NO) plus oxygen to subjects with submassive pulmonary embolism (PE) will improve right ventricular (RV) systolic function and reduce RV strain and necrosis, while improving patient dyspnea, more than treatment with oxygen alone.MethodsThis article describes the rationale and protocol for a registered (NCT01939301), nearly completed phase II, 3-center, randomized, double-blind, controlled trial. Eligible patients have pulmonary imaging-proven acute PE. Subjects must be normotensive, and have RV dysfunction on echocardiography or elevated troponin or brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen or placebo for 24 hours (±3 hours) with blood sampling before and after treatment, and mandatory echocardiography and high-sensitivity troponin posttreatment to assess the composite primary end point. The sample size of N=78 was predicated on 30% more NO-treated patients having a normal high-sensitivity troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with α=.05 and β=.20. Safety was ensured by continuous spectrophotometric monitoring of percentage of methemoglobinemia and a predefined protocol to respond to emergent changes in condition. Blinding was ensured by identical tanks, software, and physical shielding of the device display and query of the clinical care team to assess blinding efficacy.ResultsWe have enrolled 78 patients over a 31-month period. No patient has been withdrawn as a result of a safety concern, and no patient has had a serious adverse event related to NO.ConclusionsWe present methods and a protocol for the first double-blinded, randomized trial of inhaled NO to treat PE.

| S-EPMC5412723 | biostudies-literature

Genetic variations in nitric oxide synthase and arginase influence exhaled nitric oxide levels in children.

Project description:BackgroundExhaled nitric oxide (FeNO) is a biomarker of airway inflammation. In the nitric oxide (NO) synthesis pathway, nitric oxide synthases (encoded by NOS1, NOS2A, and NOS3) and arginases (encoded by ARG1 and ARG2) compete for L-arginine. Although FeNO levels are higher in children with asthma/allergy, influence of these conditions on the relationships between variations in these genes and FeNO remains unknown. The aims of the study were to evaluate the role of genetic variations in nitric oxide synthases and arginases on FeNO in children and to assess the influence of asthma and respiratory allergy on these genetic associations.MethodsAmong children (6-11 years) who participated in the southern California Children's Health Study, variations in these five genetic loci were characterized by tagSNPs. FeNO was measured in two consecutive years (N = 2298 and 2515 in Years 1 and 2, respectively). Repeated measures analysis of variance was used to evaluate the associations between these genetic variants and FeNO.ResultsSequence variations in the NOS2A and ARG2 loci were globally associated with FeNO (P = 0.0002 and 0.01, respectively). The ARG2 association was tagged by intronic variant rs3742879 with stronger association with FeNO in asthmatic children (P-interaction = 0.01). The association of a NOS2A promoter haplotype with FeNO varied significantly by rs3742879 genotypes and by asthma.ConclusionVariants in the NO synthesis pathway genes jointly contribute to differences in FeNO concentrations. Some of these genetic influences were stronger in children with asthma. Further studies are required to confirm our findings.

| S-EPMC3058253 | biostudies-literature

Exhaled nitric oxide in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Project description:BackgroundFractional exhaled nitric oxide (FENO) is a useful and noninvasive biomarker for eosinophilic airway inflammation, particularly in asthma. However, its utility in chronic obstructive pulmonary disease (COPD) remains controversial. In this study, we performed a systematic review and meta-analysis to evaluate FENO levels in COPD.MethodsA search of PubMed, Embase, Cochrane Library, and clinical trial registry was conducted from inception to January 2018. Studies were included if they reported FENO levels in patients with COPD and healthy controls. We then extracted relevant information and analyzed data. Standard mean difference (SMD) with 95% confidence interval (CI) was applied in this meta-analysis.ResultsA total of 2,073 studies were reviewed for eligibility, with 24 studies pooled for analysis. The FENO levels in patients with COPD were elevated mildly compared with healthy controls (SMD 1.28, 95% CI 0.60-1.96). A similar result was also observed in stable COPD, with an SMD of 1.21 (95% CI 0.47-1.96). On the other hand, we found no association between FENO levels and exacerbated COPD. Additionally, for patients with COPD, ex-smokers had higher levels of FENO than current smokers (SMD 2.05, 95% CI 1.13-2.97).ConclusionOur studies demonstrated a mild elevation of FENO in COPD, and the association between exacerbated COPD and FENO levels needs to be further explored. The potential mechanism is still unknown and conflicting.

| S-EPMC6124452 | biostudies-literature

Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism.

Project description:BACKGROUND:We test if inhaled nitric oxide (NO) attenuates platelet functional and metabolic hyper-reactivity in subjects with submassive pulmonary embolism (PE). METHODS:Participants with PE were randomized to either 50 ppm NO + O2 or O2 only for 24 h with blood sampling at enrollment and after treatment; results were compared with healthy controls. Platelet metabolic activity was assessed by oxygen consumption (basal and uncoupled) and reactivity was assessed with agonist-stimulated thromboelastography (TEG) and fluorometric measurement of agonist-stimulated cytosolic [Ca++] without and with pharmacological soluble guanylate (sGC) modulation. RESULTS:Participants (N = 38 per group) were well-matched at enrollment for PE severity, comorbidities as well as TEG parameters and platelet O2 consumption. NO treatment doubled the mean plasma [NO3-] (P < 0.001) indicating successful delivery, but placebo treatment produced no change. After 24 h, neither TEG nor O2 consumption parameters differed significantly between treatment groups. Platelet cytosolic [Ca++] was elevated with PE versus controls, and was decreased by treatment with cinaciguat (an sGC activator), but not riociguat (an sGC stimulator). Stimulated platelet lysate sGC activity was increased with PE compared with controls. CONCLUSIONS:In patients with acute submassive PE, despite evidence of adequate drug delivery, inhaled NO had no major effect on platelet O2 consumption or agonist-stimulated parameters on TEG. Pharmacological activation, but not stimulation, of sGC effectively decreased platelet cytosolic [Ca++], and platelet sGC activity was increased with PE, confirming the viability of sGC as a therapeutic target.

| S-EPMC7032016 | biostudies-literature

Putative Biomarkers for Acute Pulmonary Embolism in Exhaled Breath Condensate.

Project description:Current diagnostic markers for pulmonary embolism (PE) are unspecific. We investigated the proteome of the exhaled breath condensate (EBC) in a porcine model of acute PE in order to identify putative diagnostic markers for PE. EBC was collected at baseline and after the induction of autologous intermediate-risk PE in 14 pigs, plus four negative control pigs. The protein profiles of the EBC were analyzed using label-free quantitative nano liquid chromatography-tandem mass spectrometry. A total of 897 proteins were identified in the EBCs from the pigs. Alterations were found in the levels of 145 different proteins after PE compared with the baseline and negative controls: albumin was among the most upregulated proteins, with 14-fold higher levels 2.5 h after PE (p-value: 0.02). The levels of 49 other proteins were between 1.3- and 17.1-fold higher after PE. The levels of 95 proteins were lower after PE. Neutrophil gelatinase-associated lipocalin (fold change 0.3, p-value < 0.01) was among the most reduced proteins 2.5 h after PE. A prediction model based on penalized regression identified five proteins including albumin and neutrophil gelatinase-associated lipocalin. The model was capable of discriminating baseline samples from EBC samples collected 2.5 h after PE correctly in 22 out of 27 samples. In conclusion, the EBC from pigs with acute PE contained several putative diagnostic markers of PE.

| S-EPMC8584843 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data