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.

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.

A two-compartment model of pulmonary nitric oxide exchange dynamics

1998 ◽  
Vol 85 (2) ◽  
pp. 653-666 ◽  
Author(s):  
Nikolaos M. Tsoukias ◽  
Steven C. George
Keyword(s):  
Nitric Oxide ◽  
Elimination Rate ◽  
Compartment Model ◽  
Phase Iii ◽  
Exhaled Breath ◽  
Dynamic Relationship ◽  
Exhaled No ◽  
Two Compartment Model ◽  
Conducting Airways ◽  
The Relationship

The relatively recent detection of nitric oxide (NO) in the exhaled breath has prompted a great deal of experimentation in an effort to understand the pulmonary exchange dynamics. There has been very little progress in theoretical studies to assist in the interpretation of the experimental results. We have developed a two-compartment model of the lungs in an effort to explain several fundamental experimental observations. The model consists of a nonexpansile compartment representing the conducting airways and an expansile compartment representing the alveolar region of the lungs. Each compartment is surrounded by a layer of tissue that is capable of producing and consuming NO. Beyond the tissue barrier in each compartment is a layer of blood representing the bronchial circulation or the pulmonary circulation, which are both considered an infinite sink for NO. All parameters were estimated from data in the literature, including the production rates of NO in the tissue layers, which were estimated from experimental plots of the elimination rate of NO at end exhalation (ENO) vs. the exhalation flow rate (V˙E). The model is able to simulate the shape of the NO exhalation profile and to successfully simulate the following experimental features of endogenous NO exchange: 1) an inverse relationship between exhaled NO concentration and V˙E, 2) the dynamic relationship between the phase III slope andV˙E, and 3) the positive relationship between ENO andV˙E. The model predicts that these relationships can be explained by significant contributions of NO in the exhaled breath from the nonexpansile airways and the expansile alveoli. In addition, the model predicts that the relationship between ENO and V˙E can be used as an index of the relative contributions of the airways and the alveoli to exhaled NO.

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.

Impact of axial diffusion on nitric oxide exchange in the lungs

2002 ◽  
Vol 93 (6) ◽  
pp. 2070-2080 ◽  
Author(s):  
Hye-Won Shin ◽  
Steven C. George
Keyword(s):  
Nitric Oxide ◽  
Longitudinal Distribution ◽  
No Production ◽  
Small Airways ◽  
Diffusing Capacity ◽  
Alveolar Region ◽  
Axial Diffusion ◽  
Maximum Flux ◽  
Exhaled No ◽  
The Impact

Nitric oxide (NO) appears in the exhaled breath and is a potentially important clinical marker. The accepted model of NO gas exchange includes two compartments, representing the airway and alveolar region of the lungs, but neglects axial diffusion. We incorporated axial diffusion into a one-dimensional trumpet model of the lungs to assess the impact on NO exchange dynamics, particularly the impact on the estimation of flow-independent NO exchange parameters such as the airway diffusing capacity and the maximum flux of NO in the airways. Axial diffusion reduces exhaled NO concentrations because of diffusion of NO from the airways to the alveolar region of the lungs. The magnitude is inversely related to exhalation flow rate. To simulate experimental data from two different breathing maneuvers, NO airway diffusing capacity and maximum flux of NO in the airways needed to be increased approximately fourfold. These results depend strongly on the assumption of a significant production of NO in the small airways. We conclude that axial diffusion may decrease exhaled NO levels; however, more advanced knowledge of the longitudinal distribution of NO production and diffusion is needed to develop a complete understanding of the impact of axial diffusion.

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.

A different analysis applied to a mathematical model on output of exhaled nitric oxide

2005 ◽  
Vol 99 (1) ◽  
pp. 378-380 ◽  
Author(s):  
Bart L. Rottier ◽  
Judith Cohen ◽  
Thom W. van der Mark ◽  
W. Rob Douma ◽  
Eric J. Duiverman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Elimination Rate ◽  
Compartment Model ◽  
Phase Iii ◽  
Exhaled Breath ◽  
Dynamic Relationship ◽  
Exhaled No ◽  
Two Compartment Model ◽  
Conducting Airways ◽  
The Relationship

The following is the abstract of the article discussed in the following letter: The relatively recent detection of nitric oxide (NO) in the exhaled breath has prompted a great deal of experimentation in an effort to understand the pulmonary exchange dynamics. There has been very little progress in theoretical studies to assist in the interpretation of the experimental results. We have developed a two-compartment model of the lungs in an effort to explain several fundamental experimental observations. The model consists of a nonexpansile compartment representing the conducting airways and an expansile compartment representing the alveolar region of the lungs. Each compartment is surrounded by a layer of tissue that is capable of producing and consuming NO. Beyond the tissue barrier in each compartment is a layer of blood representing the bronchial circulation or the pulmonary circulation, which are both considered an infinite sink for NO. All parameters were estimated from data in the literature, including the production rates of NO in the tissue layers, which were estimated from experimental plots of the elimination rate of NO at end exhalation (ENO) vs. the exhalation flow rate (V̇e). The model is able to simulate the shape of the NO exhalation profile and to successfully simulate the following experimental features of endogenous NO exchange: 1) an inverse relationship between exhaled NO concentration and V̇E, 2) the dynamic relationship between the phase III slope and V̇E, and 3) the positive relationship between ENO and V̇E. The model predicts that these relationships can be explained by significant contributions of NO in the exhaled breath from the nonexpansile airways and the expansile alveoli. In addition, the model predicts that the relationship between ENO and V̇E can be used as an index of the relative contributions of the airways and the alveoli 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 Single-exhalation profiles of NO and CO2 in humans: effect of dynamically changing flow rate

1998 ◽  
Vol 85 (2) ◽  
pp. 642-652 ◽  
Author(s):  
Nikolaos M. Tsoukias ◽  
Ziad Tannous ◽  
Archie F. Wilson ◽  
Steven C. George
Keyword(s):  
Flow Rate ◽  
Dead Space ◽  
Human Subjects ◽  
Elimination Rate ◽  
Ambient Air ◽  
Average Concentration ◽  
Phase Iii ◽  
Breath Hold ◽  
Exhaled Breath ◽  
Exhaled No

Endogenous production of nitric oxide (NO) in the human lungs has many important pathophysiological roles and can be detected in the exhaled breath. An understanding of the factors that dictate the shape of the NO exhalation profile is fundamental to our understanding of normal and diseased lung function. We collected single-exhalation profiles of NO and CO2 from normal human subjects after inhalation of ambient air (∼15 parts/billion) and examined the effect of a 15-s breath hold and exhalation flow rate (V˙E) on the following features of the NO profile: 1) series dead space, 2) average concentration in phase III with respect to time and volume, 3) normalized slope of phase III with respect to time and volume, and 4) elimination rate at end exhalation. The dead space is ∼50% smaller for NO than for CO2 and is substantially reduced after a breath hold. The concentration of exhaled NO is inversely related to V˙E, but the average NO concentration with respect to time has a stronger inverse relationship than that with respect to volume. The normalized slope of phase III NO with respect to time and that with respect to volume are negative at a constantV˙E but can be made to change signs if the flow rate continuously decreases during the exhalation. In addition, NO elimination at end exhalation vs.V˙E produces a nonzero intercept and slope that are subject dependent and can be used to quantitate the relative contribution of the airways and the alveoli to exhaled NO. We conclude that exhaled NO has an airway and an alveolar source.

Mathematical Modeling of Different Molecule Removal on On-Line Haemodiafiltration: Influence of Dialysis Duration and Infusion Flow

2015 ◽  
Vol 39 (4) ◽  
pp. 288-296 ◽  
Author(s):  
Francisco Maduell ◽  
Juan Sanchez ◽  
Marta Net ◽  
Miquel Gomez ◽  
Jose M. Gonzalez ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Treatment Time ◽  
Compartment Model ◽  
Dialysis Dose ◽  
Β2 Microglobulin ◽  
Dialysis Duration ◽  
Two Compartment Model ◽  
On Line ◽  
The Impact ◽  
Kinetics Of

Background: In a previous study on a nocturnal, every-other-day online haemodiafiltration scheme, different removal patterns were observed for urea, creatinine, β2-​microglobulin, myoglobin and prolactin. The aim of this study was to evaluate the influence of dialysis duration and infusion flow (Qi) on the removal of different molecular weight (MW) solutes, and to quantify the effect of the different treatments on the kinetics of the solutes by using a classical two-compartment model. Methods: This prospective, in-center study was carried out in 10 patients on a nocturnal, every-other-day online post-dilution haemodiafiltration program. Each patient received four dialysis sessions with different conditions, two 4-h sessions (with infusion flows of 50 or 100 ml/min) and two 8-h sessions (with infusion flows of 50 or 100 ml/min). To analyze the solute kinetics, blood samples were obtained hourly during the dialysis treatments and in the first 3 h post-dialysis. Results: Removal patterns differed in the molecules studied, which were quantified by means of the two-compartment mathematical model. The main results show the impact of dialysis duration on the removal of low molecular weight molecules (urea and creatinine), while the impact of Qi is clearly shown for high molecular weight molecules (myoglobin and prolactin). For middle molecular weight solutes, such as β2-microglobulin, both factors (duration and Qi) enhance the removal efficiency of the dialyzer. Conclusions: Our study evaluates experimentally and mathematically how treatment time and infusion flow affect the filtration of solutes of different MW during post-dilution haemodiafiltration. The results provided by the present study should help physicians to select and individualise the most appropriate schedules to deliver an optimum diffusive and convective dialysis dose for each patient.

Sign in / Sign up

Export Citation Format

Share Document