Examining axial diffusion of nitric oxide in the lungs using heliox and breath hold

2006 ◽  
Vol 100 (2) ◽  
pp. 623-630 ◽  
Author(s):  
Hye-Won Shin ◽  
Peter Condorelli ◽  
Steven C. George
Keyword(s):  
Nitric Oxide ◽  
Muscle Tone ◽  
Hold Time ◽  
Healthy Adults ◽  
Breath Hold ◽  
Airway Wall ◽  
Axial Diffusion ◽  
Insufflating Gas ◽  
Independent Parameters ◽  
Single Path

Exhaled nitric oxide (NO) is highly dependent on exhalation flow; thus exchange dynamics of NO have been described by multicompartment models and a series of flow-independent parameters that describe airway and alveolar exchange. Because the flow-independent NO airway parameters characterize features of the airway tissue (e.g., wall concentration), they should also be independent of the physical properties of the insufflating gas. We measured the total mass of NO exhaled ( AI,II) from the airways after five different breath-hold times (5–30 s) in healthy adults (21–38 yr, n = 9) using air and heliox as the insufflating gas, and then modeled AI,II as a function of breath-hold time to determine airway NO exchange parameters. Increasing breath-hold time results in an increase in AI,II for both air and heliox, but AI,II is reduced by a mean (SD) of 31% (SD 6) ( P < 0.04) in the presence of heliox, independent of breath-hold time. However, mean (SD) values (air, heliox) for the airway wall diffusing capacity [3.70 (SD 4.18), 3.56 pl·s−1·ppb−1 (SD 3.20)], the airway wall concentration [1,439 (SD 487), 1,503 ppb (SD 644>)], and the maximum airway wall flux [4,156 (SD 2,502), 4,412 pl/s (SD 2,906)] using a single-path trumpet-shaped airway model that considers axial diffusion were independent of the insufflating gas ( P > 0.55). We conclude that a single-path trumpet model that considers axial diffusion captures the essential features of airway wall NO exchange and confirm earlier reports that the airway wall concentration in healthy adults exceeds 1 ppm and thus approaches physiological concentrations capable of modulating smooth muscle tone.

A new and more accurate technique to characterize airway nitric oxide using different breath-hold times

2005 ◽  
Vol 98 (5) ◽  
pp. 1869-1877 ◽  
Author(s):  
Hye-Won Shin ◽  
Peter Condorelli ◽  
Steven C. George
Keyword(s):  
Nitric Oxide ◽  
Muscle Tone ◽  
Experimental Studies ◽  
Significant Loss ◽  
Healthy Adults ◽  
New Technique ◽  
Breath Hold ◽  
Airway Wall ◽  
Axial Diffusion ◽  
Order Of Magnitude

Exhaled nitric oxide (NO) arises from both airway and alveolar regions of the lungs, which provides an opportunity to characterize region-specific inflammation. Current methodologies rely on vital capacity breathing maneuvers and controlled exhalation flow rates, which can be difficult to perform, especially for young children and individuals with compromised lung function. In addition, recent theoretical and experimental studies demonstrate that gas-phase axial diffusion of NO has a significant impact on the exhaled NO signal. We have developed a new technique to characterize airway NO, which requires a series of progressively increasing breath-hold times followed by exhalation of only the airway compartment. Using our new technique, we determined values (means ± SE) in healthy adults (20–38 yr, n = 8) for the airway diffusing capacity [4.5 ± 1.6 pl·s−1·parts per billion (ppb)−1], the airway wall concentration (1,340 ± 213 ppb), and the maximum airway wall flux (4,350 ± 811 pl/s). The new technique is simple to perform, and application of this data to simpler models with cylindrical airways and no axial diffusion yields parameters consistent with previous methods. Inclusion of axial diffusion as well as an anatomically correct trumpet-shaped airway geometry results in significant loss of NO from the airways to the alveolar region, profoundly impacting airway NO characterization. In particular, the airway wall concentration is more than an order of magnitude larger than previous estimates in healthy adults and may approach concentrations (∼5 nM) that can influence physiological processes such as smooth muscle tone in disease states such as asthma.

scholarly journals Flow-independent nitric oxide exchange parameters in healthy adults

2001 ◽  
Vol 91 (5) ◽  
pp. 2173-2181 ◽  
Author(s):  
Hye-Won Shin ◽  
Christine M. Rose-Gottron ◽  
Federico Perez ◽  
Dan M. Cooper ◽  
Archie F. Wilson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Flow Rate ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Hold Time ◽  
Compartment Model ◽  
Healthy Adults ◽  
New Technique ◽  
Breath Hold ◽  
Two Compartment Model

Currently accepted techniques utilize the plateau concentration of nitric oxide (NO) at a constant exhalation flow rate to characterize NO exchange, which cannot sufficiently distinguish airway and alveolar sources. Using nonlinear least squares regression and a two-compartment model, we recently described a new technique (Tsoukias et al. J Appl Physiol 91: 477–487, 2001), which utilizes a preexpiratory breath hold followed by a decreasing flow rate maneuver, to estimate three flow-independent NO parameters: maximum flux of NO from the airways ( J NO,max, pl/s), diffusing capacity of NO in the airways ( D NO,air, pl · s−1 · ppb−1), and steady-state alveolar concentration (Calv,ss, ppb). In healthy adults ( n = 10), the optimal breath-hold time was 20 s, and the mean (95% intramaneuver, intrasubject, and intrapopulation confidence interval) J NO,max, D NO,air, and Calv,ss are 640 (26, 20, and 15%) pl/s, 4.2 (168, 87, and 37%) pl · s−1 · ppb−1, and 2.5 (81, 59, and 21%) ppb, respectively. J NO,maxcan be estimated with the greatest certainty, and the variability of all the parameters within the population of healthy adults is significant. There is no correlation between the flow-independent NO parameters and forced vital capacity or the ratio of forced expiratory volume in 1 s to forced vital capacity. With the use of these parameters, the two-compartment model can accurately predict experimentally measured plateau NO concentrations at a constant flow rate. We conclude that this new technique is simple to perform and can simultaneously characterize airway and alveolar NO exchange in healthy adults with the use of a single breathing maneuver.

scholarly journals Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

2004 ◽  
Vol 97 (3) ◽  
pp. 874-882 ◽  
Author(s):  
Hye-Won Shin ◽  
Peter Condorelli ◽  
Christine M. Rose-Gottron ◽  
Dan M. Cooper ◽  
Steven C. George
Keyword(s):  
Nitric Oxide ◽  
Flow Rate ◽  
Compartment Model ◽  
Breath Hold ◽  
Axial Diffusion ◽  
Molecular Diffusivity ◽  
Exhaled No ◽  
Two Compartment Model ◽  
Insufflating Gas ◽  
The Impact

Exhaled nitric oxide (NO) is a potential noninvasive index of lung inflammation and is thought to arise from the alveolar and airway regions of the lungs. A two-compartment model has been used to describe NO exchange; however, the model neglects axial diffusion of NO in the gas phase, and recent theoretical studies suggest that this may introduce significant error. We used heliox (80% helium, 20% oxygen) as the insufflating gas to probe the impact of axial diffusion (molecular diffusivity of NO is increased 2.3-fold relative to air) in healthy adults (21–38 yr old, n = 9). Heliox decreased the plateau concentration of exhaled NO by 45% (exhalation flow rate of 50 ml/s). In addition, the total mass of NO exhaled in phase I and II after a 20-s breath hold was reduced by 36%. A single-path trumpet model that considers axial diffusion predicts a 50% increase in the maximum airway flux of NO and a near-zero alveolar concentration (CaNO) and source. Furthermore, when NO elimination is plotted vs. constant exhalation flow rate (range 50–500 ml/s), the slope has been previously interpreted as a nonzero CaNO (range 1–5 ppb); however, the trumpet model predicts a positive slope of 0.4–2.1 ppb despite a zero CaNO because of a diminishing impact of axial diffusion as flow rate increases. We conclude that axial diffusion leads to a significant backdiffusion of NO from the airways to the alveolar region that significantly impacts the partitioning of airway and alveolar contributions to exhaled NO.

A single-breath technique with variable flow rate to characterize nitric oxide exchange dynamics in the lungs

2001 ◽  
Vol 91 (1) ◽  
pp. 477-487 ◽  
Author(s):  
Nikolaos M. Tsoukias ◽  
Hye-Won Shin ◽  
Archie F. Wilson ◽  
Steven C. George
Keyword(s):  
Nitric Oxide ◽  
Flow Rate ◽  
A Priori Estimates ◽  
Hold Time ◽  
New Technique ◽  
Breath Hold ◽  
No Production ◽  
Healthy Human ◽  
Mean Values ◽  
Breathing Maneuver

Current techniques to estimate nitric oxide (NO) production and elimination in the lungs are inherently nonspecific or are cumbersome to perform (multiple-breathing maneuvers). We present a new technique capable of estimating key flow-independent parameters characteristic of NO exchange in the lungs: 1) the steady-state alveolar concentration (Calv,ss), 2) the maximum flux of NO from the airways ( J NO,max), and 3) the diffusing capacity of NO in the airways ( D NO,air). Importantly, the parameters were estimated from a single experimental single-exhalation maneuver that consisted of a preexpiratory breath hold, followed by an exhalation in which the flow rate progressively decreased. The mean values for J NO,max, D NO,air, and Calv,ss do not depend on breath-hold time and range from 280–600 pl/s, 3.7–7.1 pl · s−1 · parts per billion (ppb)−1, and 0.73–2.2 ppb, respectively, in two healthy human subjects. A priori estimates of the parameter confidence intervals demonstrate that a breath hold no longer than 20 s may be adequate and that J NO,max can be estimated with the smallest uncertainty and D NO,air with the largest, which is consistent with theoretical predictions. We conclude that our new technique can be used to characterize flow-independent NO exchange parameters from a single experimental single-exhalation breathing maneuver.

scholarly journals Reference equations for pulmonary diffusing capacity of carbon monoxide and nitric oxide in adult Caucasians

2018 ◽  
Vol 52 (1) ◽  
pp. 1500677 ◽  
Author(s):  
Mathias Munkholm ◽  
Jacob Louis Marott ◽  
Lars Bjerre-Kristensen ◽  
Flemming Madsen ◽  
Ole Find Pedersen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hold Time ◽  
Specific Conductance ◽  
Breath Hold ◽  
Diffusing Capacity ◽  
Single Breath ◽  
Capillary Membrane ◽  
Reference Equations ◽  
Hb Concentration

The aim of this study was to determine reference equations for the combined measurement of diffusing capacity of the lung for carbon monoxide (CO) and nitric oxide (NO) (DLCONO). In addition, we wanted to appeal for consensus regarding methodology of the measurement including calculation of diffusing capacity of the alveolo-capillary membrane (Dm) and pulmonary capillary volume (Vc).DLCONO was measured in 282 healthy individuals aged 18–97 years using the single-breath technique and a breath-hold time of 5 s (true apnoea period). The following values were used: 1) specific conductance of nitric oxide (θNO)=4.5 mLNO·mLblood−1·min−1·mmHg−1; 2) ratio of diffusing capacity of the membrane for NO and CO (DmNO/DmCO)=1.97; and 3) 1/red cell CO conductance (1/θCO)=(1.30+0.0041·mean capillary oxygen pressure)·(14.6/Hb concentration in g·dL−1).Reference equations were established for the outcomes of DLCONO, including DLCO and DLNO and the calculated values Dm and Vc. Independent variables were age, sex, height and age squared.By providing new reference equations and by appealing for consensus regarding the methodology, we hope to provide a basis for future studies and clinical use of this novel and interesting method.

Modeling pulmonary nitric oxide exchange

2004 ◽  
Vol 96 (3) ◽  
pp. 831-839 ◽  
Author(s):  
Steven C. George ◽  
Marieann Hogman ◽  
Solbert Permutt ◽  
Philip E. Silkoff
Keyword(s):  
Nitric Oxide ◽  
Analytical Techniques ◽  
Compartment Model ◽  
Exhaled Breath ◽  
Airway Wall ◽  
Exhaled No ◽  
Two Compartment Model ◽  
Health And Disease ◽  
Independent Parameters ◽  
Marked Dependence

Nitric oxide (NO) was first detected in the exhaled breath more than a decade ago and has since been investigated as a noninvasive means of assessing lung inflammation. Exhaled NO arises from the airway and alveolar compartments, and new analytical methods have been developed to characterize these sources. A simple two-compartment model can adequately represent many of the observed experimental observations of exhaled concentration, including the marked dependence on exhalation flow rate. The model characterizes NO exchange by using three flow-independent exchange parameters. Two of the parameters describe the airway compartment (airway NO diffusing capacity and either the maximum airway wall NO flux or the airway wall NO concentration), and the third parameter describes the alveolar region (steady-state alveolar NO concentration). A potential advantage of the two-compartment model is the ability to partition exhaled NO into an airway and alveolar source and thus improve the specificity of detecting altered NO exchange dynamics that differentially impact these regions of the lungs. Several analytical techniques have been developed to estimate the flow-independent parameters in both health and disease. Future studies will focus on improving our fundamental understanding of NO exchange dynamics, the analytical techniques used to characterize NO exchange dynamics, as well as the physiological interpretation and the clinical relevance of the flow-independent parameters.

Assessment of exhaled nitric oxide kinetics in healthy infants

2003 ◽  
Vol 94 (6) ◽  
pp. 2384-2390 ◽  
Author(s):  
T. Martı́nez ◽  
A. Weist ◽  
T. Williams ◽  
C. Clem ◽  
P. Silkoff ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Exhaled Nitric Oxide ◽  
Forced Expiration ◽  
Airway Wall ◽  
Compression Technique ◽  
Exhaled No ◽  
Healthy Infants ◽  
Dependent Flow ◽  
Independent Parameters ◽  
Exchange Parameters

Exhaled nitric oxide (Fe NO) measurements provide a noninvasive approach to the evaluation of airway inflammation. Flow-independent NO exchange parameters [airway NO transfer factor (DNO) and airway wall NO concentration (CwNO)] can be estimated from Fe NO measurements at low flows and may elucidate mechanisms of disturbances in NO exchange. We measured Fe NO in sedated infants by using an adaptation of a raised lung volume rapid thoracic compression technique that creates forced expiration through a mass-flow controller that lasts 5–10 s, at a constant preset flow. We measured Fe NO at expired flows of 50, 25, and 15 ml/s in five healthy infants (7–31 mo). Median Fe NO increased [24, 40, and 60 parts per billion (ppb)] with decreasing expiratory flows (50, 25, and 15 ml/s). Group median (range) for DNO and CwNO were 12.7 (3.2–37) × 10−3nl · s−1 · ppb−1and 108.9 (49–385) ppb, respectively, similar to values reported in healthy adults. Exhaled NO is flow dependent; flow-independent parameters of exhaled NO kinetics can be assessed in infants and are similar to values described in adults.

scholarly journals Standardisation and application of the single-breath determination of nitric oxide uptake in the lung

2017 ◽  
Vol 49 (2) ◽  
pp. 1600962 ◽  
Author(s):  
Gerald S. Zavorsky ◽  
Connie C.W. Hsia ◽  
J. Michael B. Hughes ◽  
Colin D.R. Borland ◽  
Hervé Guénard ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hold Time ◽  
Haemoglobin Concentration ◽  
Specific Conductance ◽  
Breath Holding ◽  
Breath Hold ◽  
Diffusing Capacity ◽  
Detection Range ◽  
Single Breath ◽  
Alveolar Oxygen

Diffusing capacity of the lung for nitric oxide (DLNO), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breathDLNO. This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar “collection” or continuously sampledviarapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4–6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40–60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension (PAO2) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min-1·mmHg-1·mL-1of blood; 6) the equation for 1/θCO should be (0.0062·PAO2+1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holdingPAO2and adjusted to an average haemoglobin concentration (male 14.6 g·dL−1, female 13.4 g·dL−1); 7) a membrane diffusing capacity ratio (DMNO/DMCO) should be 1.97, based on tissue diffusivity.

Skin Cooling on Breath-Hold Duration and Predicted Emergency Air Supply Duration During Immersion

2020 ◽  
Vol 91 (7) ◽  
pp. 578-585
Author(s):  
Victory C. Madu ◽  
Heather Carnahan ◽  
Robert Brown ◽  
Kerri-Ann Ennis ◽  
Kaitlyn S. Tymko ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Hold Time ◽  
Whole Body ◽  
Breath Hold ◽  
Endurance Time ◽  
Skin Exposure ◽  
Breathing Apparatus ◽  
Air Supply ◽  
Skin Cooling ◽  
Breath Hold Duration

PURPOSE: This study was intended to determine the effect of skin cooling on breath-hold duration and predicted emergency air supply duration during immersion.METHODS: While wearing a helicopter transport suit with a dive mask, 12 subjects (29 ± 10 yr, 78 ± 14 kg, 177 ± 7 cm, 2 women) were studied in 8 and 20°C water. Subjects performed a maximum breath-hold, then breathed for 90 s (through a mouthpiece connected to room air) in five skin-exposure conditions. The first trial was out of water for Control (suit zipped, hood on, mask off). Four submersion conditions included exposure of the: Partial Face (hood and mask on); Face (hood on, mask off); Head (hood and mask off); and Whole Body (suit unzipped, hood and mask off).RESULTS: Decreasing temperature and increasing skin exposure reduced breath-hold time (to as low as 10 ± 4 s), generally increased minute ventilation (up to 40 ± 15 L · min−1), and decreased predicted endurance time (PET) of a 55-L helicopter underwater emergency breathing apparatus. In 8°C water, PET decreased from 2 min 39 s (Partial Face) to 1 min 11 s (Whole Body).CONCLUSION: The most significant factor increasing breath-hold and predicted survival time was zipping up the suit. Face masks and suit hoods increased thermal comfort. Therefore, wearing the suits zipped with hoods on and, if possible, donning the dive mask prior to crashing, may increase survivability. The results have important applications for the education and preparation of helicopter occupants. Thermal protective suits and dive masks should be provided.Madu VC, Carnahan H, Brown R, Ennis K-A, Tymko KS, Hurrie DMG, McDonald GK, Cornish SM, Giesbrecht GG. Skin cooling on breath-hold duration and predicted emergency air supply duration during immersion. Aerosp Med Hum Perform. 2020; 91(7):578–585.

Modulation of cerebral arterial tone by endothelium-derived relaxing factor

1993 ◽  
Vol 264 (4) ◽  
pp. H1245-H1250 ◽  
Author(s):  
J. E. Brian ◽  
R. H. Kennedy
Keyword(s):  
Nitric Oxide ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Maximum Tension ◽  
Relaxing Factor ◽  
Middle Cerebral Arteries ◽  
Endothelium Derived Relaxing Factor ◽  
Vascular Smooth Muscle Tone ◽  
Dose Dependent ◽  
Arterial Tone

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.

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