Peak Nitric Oxide Concentration Research Articles

Nitric Oxide Concentration: A New Data Set Derived From SABER Measurements

AbstractVertical profiles of nitric oxide (NO) concentration are derived between 120 and 250 km using updated NO emission rates measured by Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite. The Naval Research Laboratory Mass Spectrometer Incoherent Scatter Radar (MSIS) 2.1 model is used to provide the required parameters of temperature, atomic oxygen number density, and molecule oxygen number density needed to derive the NO concentrations using a non‐local thermodynamic equilibrium (non‐LTE) model. The SABER NO concentration shows a significant correlation with solar activity with larger peak NO concentrations and higher altitude extent during solar maximum years compared to those during the solar minimum years. The SABER NO agrees well with the MSIS 2.1 NO at altitudes above 120 km for all latitudes, while the pronounced SABER‐MSIS NO discrepancy below 120 km is likely due to the temperature underestimation by MSIS 2.1. A detailed error analysis is presented and considers systematic and random errors in all the terms in the non‐LTE model used to derive the NO concentration. Random error in MSIS 2.1 temperature and atomic oxygen dominates the uncertainty in single NO profiles above 120 km. We estimated a systematic error up to ∼36% between 120 and 250 km during solar maximum years.

Sounding Rocket Observation of Nitric Oxide in the Polar Night

AbstractAn altitude profile of Nitric Oxide (NO) in the 80–110 km altitude range was measured in the polar night from a sounding rocket on 27 January 2020. The observations were made using the technique of stellar occultation with a UV spectrograph observing the γ (1,0) band of NO near 215 nm. The tangent point for the altitude profile was at 74° latitude, a location that had been in darkness for 80 days. The retrieved slant column density profile is interpreted using an assumed four‐parameter analytic profile shape. Retrievals of the fitting parameters yield a profile with a peak NO concentration of 2.2 ± 0.7 × 108 cm−3 at 93.5 ± 4.1 km. The observations were made during a time of minimum solar and geomagnetic activity. The NO maximum retrieved from the rocket profile is significantly larger in abundance and lower in altitude than other observations on the same day at nearby latitudes just outside the polar night. These rocket‐borne results are consistent with NO that is created over the course over the polar winter and is confined to high latitudes in the polar night by the mesospheric polar vortex. During the course of that confinement the abundance increases due to the lack of photodissociation, allowing the NO to descend. We show that the observed descent can be explained by eddy diffusion‐driven transport, though vertical advection cannot be ruled out.

An electrochemical nitric oxide biosensor based on immobilized cytochrome c on a chitosan-gold nanocomposite modified gold electrode

Goldnanoparticle (AuNPs), chitosan (CS), cytochrome c (Cyt c) and Nafion were immobilized on the surface of a gold electrode to form a Nafion/Cyt c/CS-3-Mercaptopropionic acid (MPA)-AuNPs/cysteamine-MPA (SAMs)-Au electrode. The CS-MPA-AuNPs nanocomposite was characterized by UV–vis spectroscopy. Electrochemical behavior of modified electrode was analyzed by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and chronoamperometry. Uv-vis results showed that CS-MPA-AuNPs nanocomposite could improve electron transfer between Cyt c and electrode surface and keep the catalytic activity of Cyt c. A pair of well defined and reversible redox peaks could be observed for the modified electrode in a 0.1M phosphate buffer solution (PBS, pH 7.0). The anodic and cathodic peak potentials of Cyt c/CS-MPA-AuNPs/SAMs-Au electrode were at 0.006V and −0.043V (vs. Ag/AgCl), respectively. Particular electrocatalytic activity was shown by Cyt c on CS-MPA-AuNPs layer for nitric oxide (NO) reduction. The relationship between peak current and NO concentration was linear in the range of 1×10−7–21.5×10−7M with a detection limit of 0.45×10−7M (S/N=3).The sensitivity was 0.199μA/μM. The obtained results indicating that the newly developed biosensor was quite selective and stable which was used for accurate and exact detection of NO.

Mathematical modeling of nitric oxide diffusion in small arterioles

The present study examined how the existence of glycocalyx layer (GLY) could influence the wall shear stress (WSS) and nitric oxide (NO) bioavailability in small arterioles. It was accomplished by considering GLY in determination of WSS, and its consequential effect on NO diffusion was predicted by a time-dependent computational model. The results showed that the WSS with consideration of GLY was not significantly different from that without the consideration. Although the difference was not statistically significant, the mean WSS with consideration of GLY was slightly greater than that without the consideration. The corresponding computational simulation to the existence of GLY showed no significant effect of GLY consideration on the peak NO concentration in the endothelium. In addition, no significant difference was found in sGC activation between with and without consideration of GLY. The above findings suggest that small changes in WSS due to the GLY existence may not significantly influence the NO transport or sGC activation in arterioles.

Picomolar Nitric Oxide Signals from Central Neurons Recorded Using Ultrasensitive Detector Cells

Nitric oxide (NO) is a widespread signaling molecule with potentially multifarious actions of relevance to health and disease. A fundamental determinant of how it acts is its concentration, but there remains a lack of coherent information on the patterns of NO release from its sources, such as neurons or endothelial cells, in either normal or pathological conditions. We have used detector cells having the highest recorded NO sensitivity to monitor NO release from brain tissue quantitatively and in real time. Stimulation of NMDA receptors, which are coupled to activation of neuronal NO synthase, routinely generated NO signals from neurons in cerebellar slices. The average computed peak NO concentrations varied across the anatomical layers of the cerebellum, from 12 to 130 pm. The mean value found in the hippocampus was 200 pm. Much variation in the amplitudes recorded by individual detector cells was observed, this being attributable to their location at variable distances from the NO sources. From fits to the data, the NO concentrations at the source surfaces were 120 pm to 1.4 nm, and the underlying rates of NO generation were 36-350 nm/s, depending on area. Our measurements are 4-5 orders of magnitude lower than reported by some electrode recordings in cerebellum or hippocampus. In return, they establish coherence between the NO concentrations able to elicit physiological responses in target cells through guanylyl cyclase-linked NO receptors, the concentrations that neuronal NO synthase is predicted to generate locally, and the concentrations that neurons actually produce.

Mechanisms of Activity-dependent Plasticity in Cellular Nitric Oxide-cGMP Signaling

Cellular responsiveness to nitric oxide (NO) is shaped by past history of NO exposure. The mechanisms behind this plasticity were explored using rat platelets in vitro, specifically to determine the relative contributions made by desensitization of NO receptors, which couple to cGMP formation, and by phosphodiesterase-5 (PDE5), which is activated by cGMP and also hydrolyzes it. Repeated delivery of brief NO pulses (50 nm peak) at 1-min intervals resulted in a progressive loss of the associated cGMP responses, which was the combined consequence of receptor desensitization and PDE5 activation, with the former dominating. Delivery of pulses of differing amplitude showed that NO stimulated and desensitized receptors with similar potency (EC50 = 10–20 nm). PDE5 activation was highly sensitive to NO, with a single pulse peaking at 2 nm being sufficient to evoke a 50% loss of response to a subsequent near-maximal NO pulse. However, the activated state of the PDE subsided quickly after removal of NO, the half-time for recovery being 25 s. In contrast, receptor desensitization reverted much more slowly, the half-time being 16 min. Accordingly, with long (20-min) exposures, NO concentrations as low as 600 pm provoked significant desensitization. The results indicate that PDE5 activation and receptor desensitization subserve distinct short term and longer term roles as mediators of plasticity in NO-cGMP signaling. A kinetic model explicitly describing the complex interplay between NO concentration, cGMP synthesis, PDE5 activation, and the resulting cGMP accumulation successfully simulated the present and previous data.

Characterization of Near-Road Pollutant Gradients Using Path-Integrated Optical Remote Sensing

Understanding motor vehicle emissions, near-roadway pollutant dispersion, and their potential impact to near-roadway populations is an area of growing environmental interest. As part of ongoing U.S. Environmental Protection Agency research in this area, a field study was conducted near Interstate 440 (I-440) in Raleigh, NC, in July and August of 2006. This paper presents a subset of measurements from the study focusing on nitric oxide (NO) concentrations near the roadway. Measurements of NO in this study were facilitated by the use of a novel path-integrated optical remote sensing technique called deep ultraviolet differential optical absorption spectroscopy (DUV-DOAS). This paper reviews the development and application of this measurement system. Time-resolved near-road NO concentrations are analyzed in conjunction with wind and traffic data to provide a picture of emissions and near-road dispersion for the study. Results show peak NO concentrations in the 150 ppb range during weekday morning rush hours with winds from the road accompanied by significantly lower afternoon and weekend concentrations. Traffic volume and wind direction are shown to be primary determinants of NO concentrations with turbulent diffusion and meandering accounting for significant near-road concentrations in off-wind conditions. The enhanced source capture performance of the open-path configuration allowed for robust comparisons of measured concentrations with a composite variable of traffic intensity coupled with wind transport (R2 = 0.84) as well as investigations on the influence of wind direction on NO dilution near the roadway. The benefits of path-integrated measurements for assessing line source impacts and evaluating models is presented. The advantages of NO as a tracer compound, compared with nitrogen dioxide, for investigations of mobile source emissions and initial dispersion under crosswind conditions are also discussed.

Martin Friedrich - Vice-Chair of the Working Group for IRI

Measurements of nitric oxide (NO) concentrations were carried out from Thumba, India, using rocket-borne radiometers. The technique of measurement is based on the detection of day-glow emissions of the NO gamma (1,0) band. The results obtained are presented in this paper. The peak NO concentration shows a very good correlation with integrated value of the solar X-ray flux in the 0.1–0.8 nm band, thereby indicating the influence of the X-ray flux on the NO concentration. The observed variability of NO is thought to be mainly due to solar activity and partly due to different X-ray flux values on the days of the flights. Theoretical model calculations for rocket flight conditions were found to be in fairly good agreement with the observed profiles. The differences below 90 km altitude in the NO profiles are thought to be due to eddy turbulence. This model is also used to study changes in the NO concentration with solar activity and latitude.

Direct gas measurements indicate that the novel cyclooxygenase inhibitor AZD3582 is an effective nitric oxide donor in vivo

1. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is a COX-inhibiting nitric oxide donor that inhibits COX-1 and COX-2. It is as effective as naproxen in models of pain and inflammation, but causes less gastroduodenal damage. Nitric oxide (NO) is generated from AZD3582 in vitro, and this study sought to show that the drug donates NO in vivo. 2. In anaesthetised male New Zealand white rabbits, the endogenous NO concentration in exhaled air was reduced by N(G)-nitro-L-arginine methyl ester (L-NAME) (30 mg kg(- 1) i.v.) from 33.5+/-1.0 ppb (mean+/-s.e.m.; n=6 per group) to 3.0+/-1.0 ppb, while increasing blood pressure and reducing heart rate. AZD3582 (0.2, 0.6, 2.0 or 6.0 micromol kg(- 1) min(- 1)) given 30 min after L-NAME increased the concentration of NO in exhaled air (P<0.05), decreased blood pressure and increased heart rate in a dose-dependent manner versus L-NAME control values. The peak mean NO concentration obtained was 44+/-8.0 ppb. 3. In in situ-perfused rabbit lungs, L-NAME (185 micromol l(- 1)) reduced the NO concentration in exhaled air from 106+/-13 to 4.0+/-0.4 ppb (n=5). Addition of AZD3582 (6 micromol min(- 1)) to the perfusate produced an initial rapid increase in the NO concentration in exhaled air, followed by a sustained, but lower plateau. Infusion of L-NAME increased, and AZD3582 decreased, pulmonary arterial pressure. 4. In both anaesthetised rabbits and in the perfused lungs, brief periods of hypoxia increased NO concentrations generated by AZD3582. 5. We conclude that, in rabbits, AZD3582 donates NO in vivo with characteristics similar to those reported for nitroglycerin and isosorbide nitrates

Multiple Single-breath Measurements of Nitric Oxide in the Intubated Patient

Multiple flow rate measurements of exhaled nitric oxide (NO) have been advocated to fractionate NO from alveolar and bronchial sources. The aim of this study was to develop a method by which multiple single-breath exhalations at various flow rates could be performed in intubated, mechanically ventilated patients. Nine patients without lung disease were studied awake and after intubation, during general anesthesia. A suction ejection system connected to a restrictor valve was used to control the exhalation flow rate. From these measurements the fraction of alveolar NO (FANO), the fraction of airway wall NO (FawNO), and the airway wall transfer rate (DNO) were calculated. The fraction of exhaled NO was reduced by 50% after intubation. DNO was also reduced by intubation (from 10 +/- 1.3 to 6.4 +/- 2.1 nl second(-1) ppb(-1) x 10(-3)) whereas neither FawNO nor FANO was affected. The peak NO concentration after 20 seconds of apnea during general anesthesia was similar to calculated FawNO. The vacuum aspiration method used in this study allowed for reproducible multiple single-breath measurements and calculation of alveolar and bronchial NO parameters. Further studies will reveal whether this methodology will improve the value of exhaled NO analysis in intubated, mechanically ventilated patients with pulmonary disease.

Dynamics of nitric oxide release in the cardiovascular system.

The endothelium plays a critical role in maintaining vascular tone by releasing nitric oxide (NO). Endothelium derived NO diffuses to smooth muscles, triggering their relaxation. The dynamic of NO production is a determining factor in signal transduction. The present studies were designed to elucidate dynamics of NO release from normal and dysfunctional endothelium. The nanosensors (diameter 100-300 nm) exhibiting a response time better than 100 micros and detection limit of 1.0 x 10(-9) mol L(-1) were used for in vitro monitoring of NO release from single endothelial cells from the iliac artery of normotensive (WKY) rats, hypertensive (SHR) rats, and normal and cholesterolemic rabbits. Also, the dynamics and distribution of NO in left ventricular wall of rabbit heart were measured. The rate of NO release was much higher (1200 +/- 50 nmol L(-1) s(-1)) for WKY than for SHR (460 +/- 10 nmol L(-1) s(-1)). Also, the peak NO concentration was about three times higher for WKY than SHR. Similar decrease in the dynamics of NO release was observed for cholesterolemic rabbits. The dynamics of NO release changed dramatically along the wall of rabbit aorta, being highest (0.86 +/- 0.12 micromol L(-1)) for the ascending aorta, and lowest for the iliac aorta (0.48 +/- 0.15 micromol L(-1)). The distribution of NO in the left ventricular wall of rabbit heart was not uniform and varied from 1.23 +/- 0.20 micromol L(-1) (center) to 0.90 +/- 0.15 micromol L(-1) (apex). Both, the maximal concentration and the dynamics of NO release can be useful diagnostic tools in estimating the level of endothelial dysfunction and cardiovascular system efficiency.

Dynamics of nitric oxide release in the cardiovascular system.

The endothelium plays a critical role in maintaining vascular tone by releasing nitric oxide (NO). Endothelium derived NO diffuses to smooth muscles, triggering their relaxation. The dynamic of NO production is a determining factor in signal transduction. The present studies were designed to elucidate dynamics of NO release from normal and dysfunctional endothelium. The nanosensors (diameter 100-300 nm) exhibiting a response time better than 100 micros and detection limit of 1.0 x 10(-9) mol L(-1) were used for in vitro monitoring of NO release from single endothelial cells from the iliac artery of normotensive (WKY) rats, hypertensive (SHR) rats, and normal and cholesterolemic rabbits. Also, the dynamics and distribution of NO in left ventricular wall of rabbit heart were measured. The rate of NO release was much higher (1200 +/- 50 nmol L(-1) s(-1)) for WKY than for SHR (460 +/- 10 nmol L(-1) s(-1)). Also, the peak NO concentration was about three times higher for WKY than SHR. Similar decrease in the dynamics of NO release was observed for cholesterolemic rabbits. The dynamics of NO release changed dramatically along the wall of rabbit aorta, being highest (0.86 +/- 0.12 micromol L(-1)) for the ascending aorta, and lowest for the iliac aorta (0.48 +/- 0.15 micromol L(-1)). The distribution of NO in the left ventricular wall of rabbit heart was not uniform and varied from 1.23 +/- 0.20 micromol L(-1) (center) to 0.90 +/- 0.15 micromol L(-1) (apex). Both, the maximal concentration and the dynamics of NO release can be useful diagnostic tools in estimating the level of endothelial dysfunction and cardiovascular system efficiency.

Dynamics of nitric oxide during simulated ischaemia‐reperfusion in rat striatal slices measured using an intrinsic biosensor, soluble guanylyl cyclase

Nitric oxide (NO) may act as a toxin in several neuropathologies, including the brain damage resulting from cerebral ischaemia. Rat striatal slices were used to determine the mechanism of enhanced NO release following simulated ischaemia and, for estimating the NO concentrations, the activity of guanylyl cyclase served as a biosensor. Exposure of the slices for 10 min to an oxygen- and glucose-free medium caused a 70% fall in cGMP levels. On recovery, cGMP increased 2-fold above basal, where it remained for 40 min before declining. The pattern of changes matched those of cGMP or NO oxidation products measured during and after brain ischaemia in vivo. The increase observed during the recovery period was blocked by inhibition of NO synthase or NMDA receptors and was curtailed by tetrodotoxin, implying that it was caused by glutamate release leading to activation of the NMDA receptor-NO synthase pathway. Calibration of the cGMP levels against NO-stimulated guanylyl cyclase yielded a basal NO concentration of 0.6 nm. The peak NO concentration achieved on recovery from simulated ischaemia was estimated as 0.8 nm. These values are compatible with the low micromolar concentrations of NO oxidation products (chiefly nitrate) found by microdialysis in vivo, providing the NO inactivation rate (forming nitrate) is accounted for. NO at a concentration around 1 nm is unlikely to be toxic to cells. However, if the NO inactivation mechanism were to fail (as it can) the NO production rate normally providing only subnanomolar NO could readily generate toxic (microM) NO concentrations.

Nasal nitric oxide and the nasal cycle.

To establish the relationship between nasal patency and the nitric oxide (NO) concentration in the nasal airways. Unilateral nasal NO concentration (n = 11) and inhaled nasal NO concentration at oropharynx (n = 9) were measured in healthy adult volunteers. Subjects breathed normally through the nose with a known resistance (ranged from none to total occlusion) placed in one nostril. In a subgroup (n = 7), the unilateral nasal NO concentrations were determined with nasal cavity congestion induced by lateral decubitus. When the added nasal resistance was less than 6 cm H(2)0 per liter per second, the peak NO concentrations in the nose remained below 80 parts per billion (ppb). Thereafter, the higher the resistance, the greater the NO concentration. It was up to 1109.7 ppb when the front nostril was totally occluded. There was no correlation between oropharyngeal NO concentrations and resistance in the front of the nose (r = 0.4). There was a significantly negative correlation between nasal cavity volumes and nasal NO concentrations (r = -0.8, P <.001). Increases in nasal resistance to levels encountered in the nasal cycle and in recumbency augments the NO concentration within the obstructed side of the nose. Although that within the nose changes with patency, the NO concentration is constant down to the lower airways. The modulation role of the upper airways to the inhaled NO concentration remains unclear.

Exhaled nitric oxide level decreases after cardiopulmonary bypass in adult patients.

To measure exhaled nitric oxide (NO) and compare it with lung function after cardiopulmonary bypass (CPB) in adult patients. Pulmonary dysfunction is sometimes observed after CPB. Impaired production of NO may account for this dysfunction. Prospective, single-center, observational study. University hospital operating room, intensive care unit. Sixteen adult patients undergoing cardiac surgery with CPB. None except cardiac surgery with CPB. Exhaled NO was measured continuously by the chemiluminescence method and was expressed as the peak and mean NO concentrations, and the NO output (VNO). These parameters were calculated by averaging four sequential tidal NO values. The data were obtained serially from before CPB to 16 hrs after CPB. Lung function was evaluated by monitoring lung compliance, pulmonary artery pressure, and alveolar-arterial oxygen difference (P(A-a)O2). The cardiac index did not change except for a significant increase at 16 hrs compared with 6 hrs after CPB. Peak NO, mean NO, and VNO decreased from 15.4 +/- 2.0 ppb (before CPB) to 8.2 +/- 0.8 ppb (6 hrs after CPB), from 5.7 +/- 0.7 ppb to 2.8 +/- 0.6 ppb, and from 29.2 +/- 3.1 nL/min to 15.7 +/- 2.2 nL/min, respectively. These changes were associated with the increases in pulmonary artery pressure and alveolar-arterial oxygen difference, and the decrease in lung compliance. VNO recovered to the level measured before CPB 16 hrs after CPB, which was consistent with the physiologic recovery in pulmonary hypertension, lung compliance, and gas exchange. Measurement of exhaled NO as VNO, which was associated with lung dysfunction, may be an indicator of lung injury in adult patients after cardiopulmonary bypass.

Microcoaxial electrode for in vivo nitric oxide measurement.

Nitric oxide (NO) is a gaseous mediator involved in various physiological phenomena, such as vasorelaxation and neurotransmission. Investigation of local cellular responses of NO production in vivo and in vitro requires a measurement method with a high spatial resolution. For selective NO measurement, we therefore developed a microcoaxial electrode whose tip diameter is less than 10 microm. Calibration using various concentrations of NO (0.1-1.0 microM) showed that the electrode has good linearity (r = 0.99) and its detection limit is 0.075 microM (S/N = 3). We verified the applicability of this electrode to in vivo and in vitro local measurement NO released from bovine aortic cultured endothelial cells (BAECs) stimulated by acetylcholine (ACh). After the addition of ACh, a transient increase in NO concentration was detected by the electrode. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), a putative NO synthase inhibitor, NO release (peak NO concentration) from RAECs was significantly less than that in the absence of L-NAME (0.18 +/- 0.04 microM vs 0.47 +/- 0.13; P < 0.01). After removal of L-NAME, NO release partially recovered (0.39 +/- 0.10 microM). In conclusion, the microcoaxial electrode was successfully applied to direct and continuous NO measurement in biological systems.

Exhaled nitric oxide and bronchoalveolar lavage nitrite/nitrate in active pulmonary sarcoidosis.

Increased exhaled nitric oxide (NO) may reflect respiratory tract inflammation in untreated asthmatics. We compared exhaled NO and bronchoalveolar lavage (BAL) nitrate/nitrite (NO3-/NO2-) in 10 patients who had untreated, active pulmonary sarcoidosis with those of normal control subjects. Exhaled NO concentrations, determined by chemiluminescence, were similar in patients and control subjects (peak NO concentration of patients [mean +/- SD]: 13.6 +/- 5.9 parts per billion [ppb], peak NO concentration of control subjects: 11.2 +/- 5.7 ppb, p = 0.32; mean alveolar NO concentration of patients: 7.8 +/- 4.4 ppb, mean alveolar NO concentration of control subjects: 7.1 +/- 4.2 ppb, p = 0.70; end-tidal NO concentration of patients: 6.9 +/- 4.5 ppb, end-tidal NO concentration of control subjects: 6.6 +/- 4.0 ppb, p = 0.60). BAL NO2- was assayed using a modified Griess reaction after reduction of NO3- to NO2-. There was no significant difference in mean BAL NO2- concentrations, expressed as nanomoles per milliliter of epithelial lining fluid (patients: 544 nmol/ml, control subjects: 579 nmol/ml, p = 0.81) or as nanomoles per milliliter of BAL fluid (patients: 6.7 nmol/ml, control subjects: 5.7 nmol/ml, p = 0.41). These data suggest that excess NO generation does not accompany the respiratory tract inflammation of pulmonary sarcoidosis.

Factors influencing the tracheal fluctuation of inhaled nitric oxide in patients with acute lung injury.

Inhaled nitric oxide (NO) improves arterial oxygenation in patients with acute lung injury (ALI) by selectively dilating pulmonary vessels perfusing ventilated lung areas. It can be hypothesized that NO uptake from the lung decreases with increasing ventilation perfusion mismatch. This study was undertaken to determine the factors influencing the fluctuation of tracheal NO concentration over the respiratory cycle as an index of NO pulmonary uptake in patients with ALI. By using a prototype system (Opti-NO) delivering a constant flow of NO only during the inspiratory phase, 3 and 6 ppm of NO were administered during controlled mechanical ventilation into a lung model and to 11 patients with ALI. All patients had a thoracic computed tomography (CT) scan. Based on an analysis of tomographic densities, lungs were divided into three zones: normally aerated (-1.000 to -500 Hounsfield units [HU]), poorly aerated (-500 to -100 HU), and nonaerated (-100 to +100 HU), and the volume of each zone was computed. Concentrations of NO in the inspiratory limb and trachea were continuously measured by a fast-response chemiluminescence apparatus. In the lung model, tracheal NO concentration was stable with minor fluctuation. In contrast, in patients, tracheal NO concentration fluctuated widely during the respiratory cycle (55 +/- 10%). Because uptake of NO from the lungs was absent in the lung model but present in the patients, this fluctuation was considered as an index of pulmonary uptake of NO. This was further substantiated by (1) the coincidence of the peak and minimum tracheal NO concentration with the end-inspiratory and end-expiratory phases, respectively, and (2) continued decrease of tracheal NO concentration during prolonged expiratory phase. In patients with ALI, the fluctuation of tracheal NO concentration expressed as the difference between inspiratory and expiratory NO concentrations divided by inspiratory NO concentration was greater at 6 ppm than at 3 ppm (P < 0.01), was linearly correlated with normally aerated lung volume, inversely correlated with alveolar dead space and with poorly aerated lung volume. In patients with ALI, fluctuation of tracheal NO concentration over the respiratory cycle can be considered as an index of NO uptake from the lungs that depends on aerated lung volume and perfusion of ventilated lung areas. At bedside, it may be used to follow the evolution of ventilation-perfusion mismatch.

Effect of measurement conditions on measured levels of peak exhaled nitric oxide.

BACKGROUND: It is possible to measure nitric oxide (NO) levels in exhaled air. The absolute concentrations of exhaled NO obtained by separate workers in similar patient groups and normal subjects...

Inaccuracies of nitric oxide delivery systems during adult mechanical ventilation.

Various systems to administer inhaled nitric oxide (NO) have been used in patients and experimental animals. We used a lung model to evaluate five NO delivery systems during mechanical ventilation with various ventilatory patterns. An adult mechanical ventilator was attached to a test lung configured to separate inspired and expired gases. Four injection systems were evaluated with NO injected either into the inspiratory circuit 90 cm proximal to the Y piece or directly at the Y piece and delivered either continuously or only during the inspiratory phase. Alternatively, NO was mixed with air using a blender and delivered to the high-pressure air inlet of the ventilator. Nitric oxide concentration was measured from the inspiratory limb of the ventilator circuit and the tracheal level using rapid- and slow-response chemiluminescence analyzers. The ventilator was set for constant-flow volume control ventilation, pressure control ventilation, pressure support ventilation, or synchronized intermittent mandatory ventilation. Tidal volumes of 0.5 l and 1 l were evaluated with inspiratory times of 1 s and 2 s. The system that premixed NO proximal to the ventilator was the only one that maintained constant NO delivery regardless of ventilatory pattern. The other systems delivered variable NO concentration during pressure control ventilation and spontaneous breathing modes. Systems that injected a continuous flow of NO delivered peak NO concentrations greater than the calculated dose. These variations were not apparent when a slow-response chemiluminescence analyzer was used. NO delivery systems that inject NO at a constant rate, either continuously or during inspiration only, into the inspiratory limb of the ventilator circuit produce highly variable and unpredictable NO delivery when inspiratory flow is not constant. Such systems may deliver a very high NO concentration to the lungs, which is not accurately reflected by measurements performed with slow-response analyzers.