Stress concentration around an atelectatic region: a finite element model.

Lung parenchyma surrounding an atelectatic region is thought to be subjected to increased stress compared with the rest of the lung. Using 37 hexagonal cells made of linear springs, Mead et al. (1970) measured a stress concentration greater than 30% in the springs surrounding a stiffer central cell. We re-examine the problem using a 2D finite element model of 500 cells made of thin filaments with a non-linear stress-strain relationship. We study the consequences of increasing the central stiff region from one to nine contiguous cells in regular hexagonal honeycombs and random Voronoi honeycombs. The honeycomb structures were uniformly expanded with strains of 15%, 30%, 45% and 55% above their resting, non-deformed geometry. The curve of biaxial stress vs. fractional area change has a similar shape to that of the pressure-volume curve of the lung, showing an initial regime with relatively flat slope and a final regime with decreasing slope, tending toward an asymptote. Regular honeycombs had little variability in the maximum stress in radially oriented filaments adjacent to the central stiff region. In contrast, some filaments in random Voronoi honeycombs were subjected to stress concentration approximately 16 times the average stress concentration in the radially oriented filaments adjacent to the stiff region. These results may have implications in selecting the appropriate strategy for mechanical ventilation in ARDS and defining a "safe" level of alveolar pressure for ventilating atelectatic lungs.

Peripheral resistance: a link between global airflow obstruction and regional ventilation distribution.

Airflow obstruction and heterogeneities in airway constriction and ventilation distribution are well-described prominent features of asthma. However, the mechanistic link between these global and regional features has not been well defined. We speculate that peripheral airway resistance (R(p)) may provide such a link. Structural and functional parameters are estimated from PET and HRCT images of asthmatic (AS) and nonasthmatic (NA) subjects measured at baseline (BASE) and post-methacholine challenge (POST). Conductances of 35 anatomically defined proximal airways are estimated from airway geometry obtained from high-resolution computed tomography (HRCT) images. Compliances of sublobar regions subtended by 19 most distal airways are estimated from changes in regional gas volume between two lung volumes. Specific ventilations (sV) of these sublobar regions are evaluated from 13NN-washout PET scans. For each pathway connecting the trachea to sublobar region, values of R(p) required to explain the sV distribution and global airflow obstruction are computed. Results show that R(p) is highly heterogeneous within each subject, but has average values consistent with global values in the literature. The contribution of R(p) to total pathway resistance (R(T)) increased substantially for POST (P < 0.0001). The fraction R(p)/R(T) was higher in AS than NA at POST (P < 0.0001) but similar at BASE (range: 0.960-0.997, median: 0.990). For POST, R(p)/R(T) range was 0.979-0.999 (NA) and 0.981-0.995 (AS). This approach allows for estimations of peripheral airway resistance within anatomically defined sublobar regions in vivo human lungs and may be used to evaluate peripheral effects of therapy in a subject specific manner.

Functional effect of longitudinal heterogeneity in constricted airways before and after lung expansion.

Heterogeneity in narrowing among individual airways is an important contributor to airway hyperresponsiveness. This paper investigates the contribution of longitudinal heterogeneity (the variability along the airway in cross-sectional area and shape) to airway resistance (R(aw)). We analyzed chest high-resolution computed tomography scans of 8 asthmatic (AS) and 9 nonasthmatic (NA) subjects before and after methacholine (MCh) challenge, and after lung expansion to total lung capacity. In each subject, R(aw) was calculated for 35 defined central airways with >2 mm diameter. Ignoring the area variability and noncircular shape results in an underestimation of R(aw) (%U(total)) that was substantial in some airways (∼50%) but generally small (median <6%). The average contribution of the underestimation of R(aw) caused by longitudinal heterogeneity in the area (%U(area)) to %U(total) was 36%, while the rest was due to the noncircularity of the shape (%U(shape)). After MCh challenge, %U(area) increased in AS and NA (P < 0.05). A lung volume increase to TLC reduced %U(total) and %U(area) in both AS and NA (P < 0.0001, except for %U(total) in AS with P < 0.01). Only in NA, %U(shape) had a significant reduction after increasing lung volume to TLC (P < 0.005). %U(area) was highly correlated, but not identical to the mean-normalized longitudinal heterogeneity in the cross-sectional area [CV(2)(A)] and %U(shape) to the average eccentricity of the elliptical shape. This study demonstrates that R(aw) calculated assuming a cylindrical shape and derived from an average area along its length may, in some airways, substantially underestimate R(aw). The observed changes in underestimations of R(aw) with the increase in lung volume to total lung capacity may be consistent with, and contribute in part to, the differences in effects of deep inhalations in airway function between AS and NA subjects.

Relationship between airway narrowing, patchy ventilation and lung mechanics in asthmatics.

Bronchoconstriction in asthma results in patchy ventilation forming ventilation defects (VDefs). Patchy ventilation is clinically important because it affects obstructive symptoms and impairs both gas exchange and the distribution of inhaled medications. The current study combined functional imaging, oscillatory mechanics and theoretical modelling to test whether the degrees of constriction of airways feeding those units outside VDefs were related to the extent of VDefs in bronchoconstricted asthmatic subjects. Positron emission tomography was used to quantify the regional distribution of ventilation and oscillatory mechanics were measured in asthmatic subjects before and after bronchoconstriction. For each subject, ventilation data was mapped into an anatomically based lung model that was used to evaluate whether airway constriction patterns, consistent with the imaging data, were capable of matching the measured changes in airflow obstruction. The degree and heterogeneity of constriction of the airways feeding alveolar units outside VDefs was similar among the subjects studied despite large inter-subject variability in airflow obstruction and the extent of the ventilation defects. Analysis of the data amongst the subjects showed an inverse relationship between the reduction in mean airway conductance, measured in the breathing frequency range during bronchoconstriction, and the fraction of lung involved in ventilation defects. The current data supports the concept that patchy ventilation is an expression of the integrated system and not just the sum of independent responses of individual airways.

Positron emission tomography imaging of regional lung function.

Regional pulmonary perfusion and ventilation can be assessed by imaging, with positron emission tomography (PET), the pulmonary kinetics of [13N]nitrogen (13N2). Because of its low solubility in blood and tissues, 13N2 infused intravenously in saline solution evolves into the alveolar airspace at first pass, where it accumulates in proportion to regional perfusion during a short apnea. In contrast, infused 13N2 is not retained in non-aerated regions, which do not exchange gas. Robust estimates of regional perfusion and shunt are obtained by modeling the pulmonary kinetics of 13N2 infused as a bolus during a short apnea. Regional ventilation is measured by modeling the washout of 13N2 after breathing is resumed. Regional gas content and dead space ventilation can be measured with inhalation of 13N2. Application of this novel functional imaging technique can further the understanding of the pathophysiology of a variety of pulmonary processes. This review briefly describes the methodological aspects of PET imaging of regional perfusion and ventilation and then focuses on insights in the pathophysiology of acute lung injury and asthma that have been gained by imaging the pulmonary kinetics of 13N2 with PET.

Modeling kinetics of infused 13NN-saline in acute lung injury.

A mathematical model was developed to estimate right-to-left shunt (Fs) and the volume of distribution of 13NN in alveolar gas (VA) and shunt tissue (Vs). The data obtained from this model are complementary to, and obtained simultaneously with, pulmonary functional positron emission tomography (PET). The model describes 13NN kinetics in four compartments: central mixing volume, gas-exchanging lung, shunting compartment, and systemic recirculation. To validate the model, five normal prone (NP) and six surfactant-depleted sheep in the supine (LS) and prone (LP) positions were studied under general anesthesia. A central venous bolus of 13NN-labeled saline was injected at the onset of apnea as PET imaging and arterial 13NN sampling were initiated. The model fit the tracer kinetics well (mean r2 = 0.93). Monte Carlo simulations showed that parameters could be accurately identified in the presence of expected experimental noise. Fs derived from the model correlated well with shunt estimates derived from O2 blood concentrations and from PET images. Fs was higher for LS (54 +/- 18%) than for LP (5 +/- 4%) and NP (1 +/- 1%, P < 0.01). VA, as a fraction of PET-measured lung gas volume, was lower for LS (0.18 +/- 0.09) than for LP (0.96 +/- 0.28, P < 0.01), whereas Vs, as a fraction of PET-measured lung tissue volume, was higher for LS (0.46 +/- 0.26) than for LP (0.05 +/- 0.08, P < 0.01). The main conclusions are as follows: 1) the model accurately describes measured arterial 13NN kinetics and provides estimates of Fs, and 2) in this animal model of acute lung injury, the fraction of available gas volume participating in gas exchange is reduced in the supine position.

Relation between structure, function, and imaging in a three-dimensional model of the lung.

Previous studies have reported morphometric models to predict function relations in the lung. These models, however, are not anatomically explicit. We have advanced a three-dimensional airway tree model to relate dynamic lung function to alterations in structure, particularly when constriction patterns are imposed heterogeneously inspecific anatomic locations. First we predicted the sensitivity of dynamic lung resistance and elastance (RL and EL) to explicit forms of potential constriction patterns. Simulations show that severe and heterogeneous peripheral airway constriction confined to a single region in the lung (apex, mid, or base) will not produce substantial alterations in whole lung properties as measured from the airway opening. Conversely, when measured RL and EL are abnormal, it is likely that significant (but not necessarily homogeneous) constriction has occurred throughout the entire airway tree. We also introduce the concept of image-assisted modeling. Here positron emission tomographic imaging data sensitive to ventilation heterogeneity is synthesized with RL and EL data to help identify which airway constriction conditions could be consistent with both data sets. An ultimate goal would be personalized predictions.

Low-pass filtering, a new method of fractal analysis: application to PET images of pulmonary blood flow.

The pattern of a spatial structure that repeats itself independently of the scale of magnification or resolution is often characterized by a fractal dimension (D). Two-dimensional low-pass filtering, which may serve as a method to assess D, was applied to functional images of pulmonary perfusion measured by positron emission tomography. The corner frequency of a low-pass filter is inversely proportional to the resolution scale. The method was applied to three types of images: random noise images, synthetic fractal images, and positron emission tomographic images of pulmonary perfusion. Images were processed with two-dimensional low-pass filters of decreasing corner frequencies, and a spatial heterogeneity index, the coefficient of variation, was calculated for each low-pass-filtered image. The natural logarithm of the coefficient of variation scaled linearly with the natural logarithm of the resolution scale for the PET images studied (average R(2) = 0.99). D ranged from 1.25 to 1.36 for the residual distribution of pulmonary perfusion after vertical gradients were removed by linear regression. D of the same data without removal of vertical gradients ranged from 1.11 to 1.14, but the fractal plots had systematic deviations from linearity and a lower linear correlation coefficient (R(2) = 0. 96). The method includes all data in the lung field and is insensitive to the effects of misregistration. We conclude that low-pass filtering offers new insights into the interpretation of D of two-dimensional functional images as a measure of the frequency content of spatial heterogeneity.

An objective analysis of the pressure-volume curve in the acute respiratory distress syndrome.

To assess the interobserver and intraobserver variability in the clinical evaluation of the quasi-static pressure-volume (P-V) curve, we analyzed 24 sets of inflation and deflation P-V curves obtained from patients with ARDS. We used a recently described sigmoidal equation to curve-fit the P-V data sets and objectively define the point of maximum compliance increase of the inflation limb (P(mci, i)) and the true inflection point of the deflation limb (P(inf,d)). These points were compared with graphic determinations of lower Pflex by seven clinicians. The graphic and curve-fitting methods were also compared for their ability to reproduce the same parameter value in data sets with reduced number of data points. The sigmoidal equation fit the P-V data with great accuracy (R(2) = 0.9992). The average of Pflex determinations was found to be correlated with P(mci,i) (R = 0.89) and P(inf,d) (R = 0.76). Individual determinations of Pflex were less correlated with the corresponding objective parameters (R = 0.67 and 0.62, respectively). Pflex + 2 cm H(2)O was a more accurate estimator of P(inf,d) (2 SD = +/-6.05 cm H(2)O) than Pflex was of P(mci,i) (2 SD = +/-8.02 cm H(2)O). There was significant interobserver variability in Pflex, with a maximum difference of 11 cm H(2)O for the same patient (SD = 1.9 cm H(2)O). Clinicians had difficulty reproducing Pflex in smaller data sets with differences as great as 17 cm H(2)O (SD = 2.8 cm H(2)O). In contrast, the curve-fitting method reproduced P(mci,i) with great accuracy in reduced data sets (maximum difference of 1.5 cm H(2)O and SD = 0.3 cm H(2)O). We conclude that Pflex rarely coincided with the point of maximum compliance increase defined by a sigmoid curve-fit with large differences in Pflex seen both among and within observers. Calculating objective parameters such as P(mci,i) or P(inf,d) from curve-fitted P-V data can minimize this large variability.

Modeling expiratory flow from excised tracheal tube laws.

Flow limitation during forced exhalation and gas trapping during high-frequency ventilation are affected by upstream viscous losses and by the relationship between transmural pressure (Ptm) and cross-sectional area (A(tr)) of the airways, i.e., tube law (TL). Our objective was to test the validity of a simple lumped-parameter model of expiratory flow limitation, including the measured TL, static pressure recovery, and upstream viscous losses. To accomplish this objective, we assessed the TLs of various excised animal tracheae in controlled conditions of quasi-static (no flow) and steady forced expiratory flow. A(tr) was measured from digitized images of inner tracheal walls delineated by transillumination at an axial location defining the minimal area during forced expiratory flow. Tracheal TLs followed closely the exponential form proposed by Shapiro (A. H. Shapiro. J. Biomech. Eng. 99: 126-147, 1977) for elastic tubes: Ptm = K(p) [(A(tr)/A(tr0))(-n) - 1], where A(tr0) is A(tr) at Ptm = 0 and K(p) is a parametric factor related to the stiffness of the tube wall. Using these TLs, we found that the simple model of expiratory flow limitation described well the experimental data. Independent of upstream resistance, all tracheae with an exponent n < 2 experienced flow limitation, whereas a trachea with n > 2 did not. Upstream viscous losses, as expected, reduced maximal expiratory flow. The TL measured under steady-flow conditions was stiffer than that measured under expiratory no-flow conditions, only if a significant static pressure recovery from the choke point to atmosphere was assumed in the measurement.

A comprehensive equation for the pulmonary pressure-volume curve.

Quantification of pulmonary pressure-volume (P-V) curves is often limited to calculation of specific compliance at a given pressure or the recoil pressure (P) at a given volume (V). These parameters can be substantially different depending on the arbitrary pressure or volume used in the comparison and may lead to erroneous conclusions. We evaluated a sigmoidal equation of the form, V = a + b[1 - e-(P-c)/d]-1, for its ability to characterize lung and respiratory system P-V curves obtained under a variety of conditions including normal and hypocapnic pneumoconstricted dog lungs (n = 9), oleic acid-induced acute respiratory distress syndrome (n = 2), and mechanically ventilated patients with acute respiratory distress syndrome (n = 10). In this equation, a corresponds to the V of a lower asymptote, b to the V difference between upper and lower asymptotes, c to the P at the true inflection point of the curve, and d to a width parameter proportional to the P range within which most of the V change occurs. The equation fitted equally well inflation and deflation limbs of P-V curves with a mean goodness-of-fit coefficient (R2) of 0.997 +/- 0.02 (SD). When the data from all analyzed P-V curves were normalized by the best-fit parameters and plotted as (V-a)/b vs. (P-c)/d, they collapsed into a single and tight relationship (R2 = 0.997). These results demonstrate that this sigmoidal equation can fit with excellent precision inflation and deflation P-V curves of normal lungs and of lungs with alveolar derecruitment and/or a region of gas trapping while yielding robust and physiologically useful parameters.

Effects of lung motion and tracer kinetics corrections on PET imaging of pulmonary function.

A method to assess the three-dimensional distribution of alveolar ventilation-perfusion ratio (VA/Q) by imaging the lungs with positron emission tomography (PET) during a constant-rate intravenous infusion of 13NN-labeled saline solution was developed by C. G. Rhodes, S. O. Valind, L. H. Brudin, P. E. Wollmer, T. Jones, P. D. Buckingham, and J. M. B. Hughes (J. Appl. Physiol. 66: 1896-1904 and 1905-1913, 1989). We have modified this methodology to obtain high-resolution, low-noise PET images of local VA/Q where lung motion artifact was eliminated by respiratory gating of image collection. In addition, we have refined and implemented the methods to assess local alveolar ventilation by imaging the washout of equilibrated 13NN and local perfusion by imaging the distribution of an intravenous bolus of 13NN-labeled saline solution during apnea. This paper experimentally evaluates the effect of the implemented modifications in mechanically ventilated and anesthetized dogs. We found that the lack of gating had no significant effect on the average recovered VA/Q, but the spatial heterogeneity [pixel-by-pixel coefficient of variation squared (CV2) = SD2/mean2] was underestimated by 14%. The lack of gating during the washout underestimated the average specific ventilation by 11% and decreased the corresponding CV2 by 50%.

Contributions of pulmonary perfusion and ventilation to heterogeneity in V(A)/Q measured by PET.

To estimate the contributions of the heterogeneity in regional perfusion (Q) and alveolar ventilation (V A) to that of ventilation-perfusion ratio (V A/Q), we have refined positron emission tomography (PET) techniques to image local distributions of Q and V A per unit of gas volume content (sQ and sV A, respectively) and V A/Q in dogs. sV A was assessed in two ways: 1) the washout of 13NN tracer after equilibration by rebreathing (sV A(i)), and 2) the ratio of an apneic image after a bolus intravenous infusion of 13NN-saline solution to an image collected during a steady-state intravenous infusion of the same solution (sV A(p)). SV A(p) was systematically higher than sV A(i) in all animals, and there was a high spatial correlation between sQ and sV A(p) in both body positions (mean correlation was 0.69 prone and 0.81 supine) suggesting that ventilation to well-perfused units was higher than to those poorly perfused. In the prone position, the spatial distributions of sQ, sV A(p), and V A/Q were fairly uniform with no significant gravitational gradients; however, in the supine position, these variables were significantly more heterogeneous, mostly because of significant gravitational gradients (15, 5.5, and -10%/cm, respectively) accounting for 73, 33, and 66% of the corresponding coefficient of variation (CV)2 values. We conclude that, in the prone position, gravitational forces in blood and lung tissues are largely balanced out by dorsoventral differences in lung structure. In the supine position, effects of gravity and structure become additive, resulting in substantial gravitational gradients in sQ and sV A(p), with the higher heterogeneity in V A/Q caused by a gravitational gradient in sQ, only partially compensated by that in sV A.

Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion.

Regional pneumoconstriction induced by alveolar hypocapnia is an important homeostatic mechanism for optimization of ventilation-perfusion matching. We used positron imaging of 13NN-equilibrated lungs to measure the distribution of regional tidal volume (VT), lung volume (VL), and lung impedance (Z) before and after left (L) pulmonary artery occlusion (PAO) in eight anesthetized, open-chest dogs. Measurements were made during eucapnic sinusoidal ventilation at 0.2 Hz with 4-cmH2O positive end expiratory pressure. Right (R) and L lung impedances (ZR and ZL) were determined from carinal pressure and positron imaging of dynamic regional VL. LPAO caused an increase in magnitude of ZL relative to magnitude of ZR, resulting in a shift in VT away from the PAO side, with a L/R magnitude of Z ratio changing from 1.20 +/- 0.07 (mean +/- SE) to 2.79 +/- 0.85 after LPAO (P < 0.05). Although mean L lung VL decreased slightly, the VL normalized parameters specific admittance and specific compliance both significantly decreased with PAO. Lung recoil pressure at 50% total lung capacity also increased after PAO. We conclude that PAO results in an increase in regional lung Z that shifts ventilation away from the affected area at normal breathing frequencies and that this effect is not due to a change in VL but reflects mechanical constriction at the tissue level.

Assessment and modeling of the physical components of human corporovenous function.

To understand and quantify specific causes of venoocclusive dysfunction, an analog model of penile hemodynamics, including a mechanism of flow limitation by subtunical veins, was developed and a detailed analytic study was conducted in patients with erectile dysfunction. Computer simulations for steady-state and transient intracavernosal conditions were carried out to study graded changes in cavernosal smooth muscle tone, subtunical venular resistance, and cavernosal and tunical compliances. The model predicted a steady-state cavernosal pressure (Pca)-infusion flow relationship with two phases: an initial phase characterized by a gradual slope up to a critical flow and a second phase characterized by a much steeper slope after limitation of subtunical venular flow. Model predictions were compared with clinical data obtained during incremental saline cavernosometry (SaC) and pharmacocavernosometry (PhC) in 13 patients with erectile dysfunction with use of a computer-controlled infusion system that automatically changed from constant-flow to constant-pressure feedback control when Pca reached the threshold of 80 mmHg. Steady-state pressure-flow and pressure-circumference relationships of the penis were analyzed and interpreted in terms of specific components of the electrical analog model. These clinical studies demonstrated that patients with a functional venoocclusive mechanism (i.e., those able to achieve 100 mmHg Pca with infusion flow rates < 60 ml/min during PhC) had a steeper initial slope of the pressure-flow relationship during SaC and a greater increase in penile circumference and Pca after intracavernosal injection of papaverine-phentolamine than those with an impaired venoocclusive mechanism. From the electrical analog model, initial steepness of the pressure-flow relationship (slope) during SaC mainly represented subtunical venular resistance, whereas maintenance of flow during PhC depended on overall function of the different components, i.e., subtunical venular resistance, cavernosal and subtunical compliances, and full relaxation of cavernosal smooth muscle. We conclude that the proposed analog model can be used to interpret and characterize clinical penile hemodynamic data and may provide guidelines for more successful management of patients with erectile dysfunction.

Ventilation distribution and regional lung impedance during partial unilateral bronchial obstruction.

Significant degrees of main-stem bronchial obstruction may not have a detectable effect on ventilation distribution at normal breathing frequencies. We determined the effect of graded left main-stem bronchial obstruction (area reduction of 50 and 70%) on the distribution of tidal volume (VT) and mean lung volume (VL) using radioactive 13NN and two-dimensional planar positron imaging in six supine anesthetized tracheotomized dogs. Measurements were made during eucapnic high-frequency oscillatory ventilation at frequencies (f) of 0.2, 1, 5, and 10 Hz. Right and left lung respiratory system complex impedance (Z) values were assessed by simultaneous measurements of dynamic regional lung volume by positron imaging and carinal pressure. The results show a progressive shift of VT away from the obstruction at f > 1 Hz, with VT left-to-right (L/R) ratios of 0.9, 0.9, 0.58, and 0.46 at f of 0.2, 1, 5, and 10 Hz, respectively, for 70% obstruction. VT shifts with f for 50% obstruction were similar but of lesser magnitude. VL L/R ratio was 0.88 and did not change with f or obstruction. The real part of Z was frequency dependent and increased at low f independent of obstruction. The real part of Z L/R ratio increased with obstruction at 5 and 10 Hz. At low f there was a difference between left and right imaginary parts of Z due to the difference in VL. There was no significant change in the imaginary part of Z as a result of obstruction. We conclude that up to a 70% unilateral bronchial obstruction is not detectable by distribution of ventilation at f < or = 1 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

Expiratory flow pattern following single-lung transplantation in emphysema.

In single lung transplantation (SLT) recipients, a "plateau" of the maximal expiratory flow volume curve (MEFV) and a "biphasic" MEFV have been reported to reflect anastomosis pathology. A plateau is defined as constant airflow over a large expired volume early in the MEFV. A biphasic MEFV has an initial period of high flow followed by a terminal low flow phase. Models of expiratory flow limitation by wave speed, however, predict that the MEFV of SLT recipients with emphysema should both be biphasic and demonstrate a plateau even without anastomosis pathology. Review of the spirometries and clinical courses of our first ten patients receiving SLT for emphysema demonstrated a biphasic MEFV, and a plateau of the MEFV in all patients. No patient showed evidence of anastomosis pathology. Independent lung spirometries, generated by a novel technique, revealed that the initial high flow phase of the MEFV came from the transplanted lung and the terminal low flow from the native emphysematous lung. The location of the flow limitation was demonstrated to be immediately downstream from the anastomosis. Therefore, the MEFV of SLT recipients with emphysema routinely demonstrates both a biphasic pattern and a plateau, neither of which necessarily reflect anastomosis pathology.

Understanding the pressure cost of ventilation: why does high-frequency ventilation work?

OBJECTIVES: To understand when the use of high-frequency ventilation would be advantageous, we formulated the problem of achieving adequate alveolar ventilation at minimal pressure cost by dividing it into two simpler problems: a) the pressure cost per unit of convective oscillatory flow; and b) the convective flow cost necessary to achieve a unit of alveolar ventilation. METHODS: Simple solutions for each of these cost functions were formulated using established models of gas exchange and lung mechanics, including the effects of lung inflation tidal volume and respiratory frequency in alveolar ventilation, nonlinear lung tissue compliance, and alveolar recruitment and derecruitment. Solutions to these models were combined to assess the total pressure cost of high-frequency ventilation as a function of the ventilatory settings and the pathophysiologic variables of the patient. MAIN RESULTS: The model predicted that for variables applicable to an infant with respiratory distress syndrome, the selection of positive end-expiratory pressure (PEEP) becomes critical because the penalties in pressure cost are amplified for both high and low values of PEEP. The selection of frequency is not as critical for frequencies > 10 Hz, although it is more important than in the normal neonatal lung. CONCLUSIONS: This analysis illustrates the importance of using high-frequency ventilation in infant respiratory distress syndrome and of optimizing the amount of PEEP. It also points out the danger of barotrauma in the derecruited lung. When the lungs are in a derecruited state, the combinations of frequency, PEEP, and tidal volume that yield adequate ventilation with safe distention of recruited alveoli are severely limited.

Analyzing 13NN lung washout curves in the presence of intraregional nonuniformities.

The use of 13NN and positron imaging provides a powerful noninvasive means of assessing regional pulmonary function. Current techniques for analyzing lung washout curves, however, are subject to error due to intraregional nonuniformities, particularly in the presence of areas with very long time constants or gas trapping. This paper presents a simple "hybrid" method for analyzing 13NN-washout studies that addresses the problems of regions of air trapping and long time constants within a region of interest. This method assumes an exponential washout form for the slow regions, estimates their fractional volume, and subtracts their contribution from the overall washout curve. The modified Stewart-Hamilton method is then applied to the remaining washout curve to calculate its ventilation. The over-all specific ventilation of the region is calculated as the volume-weighted average of the specific ventilations of the two compartments. The performance of the hybrid method is compared with other currently used correction techniques by using a simulated two-compartment lung washout in which there is a variable amount of gas trapping. The analysis techniques are also applied to washout data with intraregional nonuniformities obtained during experimentally created unilateral bronchial obstruction. This new approach has the advantages of automatically correcting for washout truncation, estimating the relative size of the trapped or slow region while eliminating its bias on the regional ventilation, and yet retaining the unrestricted and robust nature of the Stewart-Hamilton method in the analysis of the well-ventilated regions.

Regional lung mechanics and gas transport in lungs with inhomogeneous compliance.

The effect of respiratory frequency (f) on the distributions of ventilation, regional gas transport, lung volume, and regional impedance was assessed with positron imaging in lungs with nonuniform lung mechanics after unilateral lung lavage. Supine dogs were studied during eucapnic oscillatory ventilation at f between 1 and 15 Hz and at a constant mean airway pressure of 5 cmH2O. Substantial differences in mean lung volume and tidal volume (VT) between lavaged and control lungs were found at all f values, but pendelluft never exceeded 2% of mouth flow. For f < or = 10 Hz, VT distributed in direct proportion to lung volume, whereas gas transport per unit of lung volume, measured from washout maneuvers, was reduced by 20% in the lavaged lung. At 15 Hz, however, the distributions of VT and gas transport approached equality between both lungs. Regional impedance was analyzed with a model that included a Newtonian resistance, an inertance, and Hildebrandt's model of tissue viscoelasticity. The data obtained from this work provide useful insights with respect to the mechanisms of gas transport during high-frequency ventilation and suggest the impact of operating frequency in clinical situations where substantial interregional heterogeneity in lung compliance could be expected.