Effects of respiratory variables on regional gas transport during high-frequency ventilation

The regional effects of tidal volume (VT), respiratory frequency, and expiratory-to-inspiratory time ratio (TE/TI) during high-frequency ventilation (HFV) were studied in anesthetized and paralyzed dogs. Regional ventilation per unit of lung volume (spVr) was assessed with a positron camera during the washout of the tracer isotope 13NN from the lungs of 12 supine dogs. From the washout data, functional images of the mean residence time (MRT) of 13NN were produced and spVr was estimated as the inverse of the regional MRT. We found that at a constant VT X f product (where f represents frequency), increasing VT resulted in higher overall lung spV through the local enhancement of the basal spVr and with little effect in the apical spVr. In contrast, increasing VT X f at constant VT increased overall ventilation without significantly affecting the distribution of spVr values. TE/TI had no substantial effect in regional spVr distribution. These findings suggest that the dependency of gas transport during HFV of the form VT2 X f is the result of a progressive regional transition in gas transport mechanism. It appears, therefore, that as VT increases, the gas transport mechanism changes from a relative inefficient dispersive mechanism, dependent on VT X f, to the more efficient mechanism of direct fresh gas convection to alveoli with high regional tidal volume-to-dead-space ratio. A mathematical model of gas transport in a nonhomogeneous lung that exhibits such behavior is presented.     

Regional mapping of gas transport during high-frequency and conventional ventilation

The effects of changing tidal volume (VT) and frequency (f) on the distribution of ventilation during high-frequency ventilation (HFV) were assessed from the washout of nitrogen-13 by positron emission tomography. Six dogs, anesthetized and paralyzed, were studied in the supine position during conventional ventilation (CV) and during HFV at f of 3, 6, and 9 Hz. In CV and HFV at 6 Hz, VT was selected to achieve eucapnic arterial partial pressure of CO2 (37 +/- 3 Torr). At 3 and 9 Hz, VT was proportionally changed so that the product of VT and f remained constant and equal to that at 6 Hz. Mean residence time (MRT) of nitrogen-13 during washout was calculated for apical, midheart, and basal transverse sections of the lung and further analyzed for gravity-dependent, cephalocaudal and radial gradients. An index of local alveolar ventilation per unit of lung volume, or specific ventilation (spV), was calculated as the reciprocal of MRT. During CV vertical gradients of regional spV were seen in all sections with ventral (nondependent) regions less ventilated than dorsal (dependent) regions. Regional nonuniformity in gas transport was greatest for HFV at 3 and 6 Hz and lowest at 9 Hz and during CV. During HFV, a central region at the base of the lungs was preferentially ventilated, resulting in a regional time-averaged tracer concentration equivalent to that of the main bronchi. Because the main bronchi were certainly receiving fresh gas, the presence of this preferentially ventilated area, whose ventilation increased with VT, strongly supports the hypothesis that direct convection of fresh gas is an important mechanism of gas transport during eucapnic HFV. Aside from the local effect of increasing overall lung ventilation, this central area probably served as an intermediate shuttle station for the transport of gas between mouth and deeper alveoli when VT was less than the anatomic dead space.     

Contributions of diffusion jet flow and cardiac activity to regional ventilation in CFV.

The magnitude and regional distribution of local gas transport during constant-flow ventilation (CFV) were quantified by imaging the washout of nitrogen 13 (13NN) from anesthetized and paralyzed mongrel dogs with positron emission tomography. Equal jet flows, through two 2-mm-ID bronchial catheters 1 cm distal to the carina, were adjusted to provide eucapnic CFV (total flow = 57.6 ml.s-1.kg-1). Basal, midheart, and apical transverse sections were studied in supine and prone anesthetized dogs. The ventilation per unit volume (sV) of selected areas was computed from local 13NN concentration vs. time curves during washout. To separate the regional contributions of CFV and cardiogenic oscillation to enhanced molecular diffusion, additional supine dogs were also studied during unilateral CFV. In this protocol the CFV jet flow was delivered to a single lung while the contralateral lung was left apneic. For each lung, washout data were obtained under CFV and apnea both living and postmortem animals. The local contributions of diffusion, CFV jet effects, and cardiac activity to gas transport were evaluated and tested for additive and multiplicative synergistic interactions. The regional distribution of gas transport during CFV was found to be highly nonuniform and characterized by higher ventilation to regions located close to the main bronchi and those located in the direction in which the CFV jet pointed. No major differences were observed between supine and prone positions. This regional pattern of ventilation distribution was found to be the result of complementary and nearly multiplicative interaction between the regional effects of the CFV jet, concentrated in the central airways, and the preferential cardiogenic gas transport enhancement in ventral regions close to the heart. The data were also analyzed with a model that divides the regional diffusive gas transport resistance into a central component, affected by the CFV jet, and a peripheral component, affected only by cardiac activity. This analysis showed substantial regional heterogeneities in the effects of the different gas transport mechanisms, which are consistent with the geometry of the bronchial tree and the location of the heart in the dog. The results indicate that regional nonuniformities must be considered when modeling gas transport in CFV.     

Gas transport during high-frequency ventilation

During high-frequency small-volume ventilation (HFV), the transport rate of gas from the mouth to a lung region is a function of two conductances (conductance is the transfer rate of a gas divided by its partial pressure difference): regional longitudinal gas conductance along the airways (Grlongi) and gas conductance between lung regions (Ginter). Grlongi per unit regional lung (gas) volume [Grlongi/(Vr beta g)] was determined during HFV in 11 anesthetized paralyzed dogs lying supine. The distribution of Grlongi/(Vr beta g) was nearly uniform during HFV when stroke volumes were less than approximately two-thirds of the Fowler dead-space volume. By contrast, the distribution of Grlongi/(Vr beta g) was nonuniform when the stroke volume exceeded approximately two-thirds of the Fowler dead-space volume and the oscillation frequency was 5 Hz. Gas conductance along the airways per unit lung gas volume [average Glongi/(V beta g)], for the entire lung, increased with stroke volume at all frequencies, but for a given product of oscillation frequency and stroke volume, the average Glongi/(V beta g) was greater when stroke volume was large and oscillation frequency was low. The average Glongi/(V beta g) increased with frequency up to a maximal value; the frequency at which the maximum occurred depended on the kinematic viscosity of the inspired gas mixture.     

Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation

Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) allows for noninvasive assessment of regional metabolic activity, an index of neutrophilic inflammation. We tested the hypothesis that, during mechanical ventilation, surfactant-depleted low-aeration lung regions present increased regional (18)F-FDG uptake suggestive of in vivo increased regional metabolic activity and inflammation. Sheep underwent unilateral saline lung lavage and were ventilated supine for 4 h (positive end-expiratory pressure = 10 cmH(2)O, tidal volume adjusted to plateau pressure = 30 cmH(2)O). We used PET scans of injected (13)N-nitrogen to compute regional perfusion and ventilation and injected (18)F-FDG to calculate (18)F-FDG uptake rate. Regional aeration was quantified with transmission scans. Whole lung (18)F-FDG uptake was approximately two times higher in lavaged than in nonlavaged lungs (2.9 ± 0.6 vs. 1.5 ± 0.3 10(-3)/min; P < 0.05). The increased (18)F-FDG uptake was topographically heterogeneous and highest in dependent low-aeration regions (gas fraction 10-50%, P < 0.001), even after correction for lung density and wet-to-dry lung ratios. (18)F-FDG uptake in low-aeration regions of lavaged lungs was higher than that in low-aeration regions of nonlavaged lungs (P < 0.05). This occurred despite lower perfusion and ventilation to dependent regions in lavaged than nonlavaged lungs (P < 0.001). In contrast, (18)F-FDG uptake in normally aerated regions was low and similar between lungs. Surfactant depletion produces increased and heterogeneously distributed pulmonary (18)F-FDG uptake after 4 h of supine mechanical ventilation. Metabolic activity is highest in poorly aerated dependent regions, suggesting local increased inflammation.     

Local gas transport in eucapnic ventilation: effects of gravity and breathing frequency

The effects of body position and respiratory frequency (f) on regional gas transport during eucapnic conventional ventilation (CV) and high-frequency ventilation (HFV) were assessed from the washout of nitrogen 13 (13NN) using positron-emission tomography. In one protocol, six dogs were ventilated with CV or HFV at f = 6 Hz and tidal volume (VT) selected supine for eucapnia. A coronal cross section of the lung base was studied in the supine, prone, and right and left lateral decubitus positions. In a second protocol, six dogs were studied prone: apical and basal cross sections were studied in CV and in HFV with f = 3 and 9 Hz at eucapnic VT. Regional alveolar ventilation per unit of lung volume (spVr) was calculated for selected regions and analyzed for gravity-dependent cephalocaudal and right-to-left gradients. In both CV and HFV, nonuniformity in spVr was highest supine and lowest prone. In CV there were vertical gradients of spVr in all body positions: nondependent less ventilated than dependent regions, particularly in the supine position. In HFV there was a moderate vertical gradient in spVr in addition to a preferentially ventilated central region in all body positions. Overall lung spV was unaffected by body position in CV but in HFV was highest supine and lowest prone. Nonuniformity in eucapnic prone HFV was unaffected by f and always higher than in CV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lung regional stress and strain as a function of posture and ventilatory mode

During positive-pressure ventilation parenchymal deformation can be assessed as strain (volume increase above functional residual capacity) in response to stress (transpulmonary pressure). The aim of this study was to explore the relationship between stress and strain on the regional level using computed tomography in anesthetized healthy pigs in two postures and two patterns of breathing. Airway opening and esophageal pressures were used to calculate stress; change of gas content as assessed from computed tomography was used to calculate strain. Static stress-strain curves and dynamic strain-time curves were constructed, the latter during the inspiratory phase of volume and pressure-controlled ventilation, both in supine and prone position. The lung was divided into nondependent, intermediate, dependent, and central regions: their curves were modeled by exponential regression and examined for statistically significant differences. In all the examined regions, there were strong but different exponential relations between stress and strain. During mechanical ventilation, the end-inspiratory strain was higher in the dependent than in the nondependent regions. No differences between volume- and pressure-controlled ventilation were found. However, during volume control ventilation, prone positioning decreased the end-inspiratory strain of dependent regions and increased it in nondependent regions, resulting in reduced strain gradient. Strain is inhomogeneously distributed within the healthy lung. Prone positioning attenuates differences between dependent and nondependent regions. The regional effects of ventilatory mode and body positioning should be further explored in patients with acute lung injury.     

Regional extravascular density of the lung in patients with acute pulmonary edema

The regional distribution of extravascular lung density (lung tissue and interstitial or alveolar fluid per unit thoracic volume) and fractional pulmonary blood volume (volume of blood per unit thoracic volume) was measured in five patients with acute interstitial pulmonary edema and two patients with acute alveolar edema. We found a uniform increase in extravascular lung density in the patients with acute interstitial edema but a preferentially dependent distribution in the patients with alveolar edema. Fractional blood volume had an abnormally uniform distribution in patients with interstitial edema. In alveolar edema, there was marked redistribution of blood volume away from severely edematous regions. The results are in agreement with previous experimental work with animal models. The distribution of extravascular lung density and fractional blood volume in subjects with acute interstitial edema is, however, different from that found in subjects with chronic interstitial edema, suggesting that the pathophysiological characteristics of the two conditions may be different.     

Ventilation and perfusion distribution during altered PEEP in the left lung in the left lateral decubitus posture with unchanged tidal volume in dogs

Previous studies in anesthetized humans positioned in the left lateral decubitus (LLD) posture have shown that unilateral positive end-expiratory pressure (PEEP) to the dependent lung produce a more even ventilation distribution and improves gas exchange. Unilateral PEEP to the dependent lung may offer special advantages during LLD surgery by reducing the alveolar-to-arterial oxygen pressure difference {(A-a)PO2 or venous admixture} in patients with thoracic trauma or unilateral lung injury. We measured the effects of unilateral PEEP on regional distribution of blood flow (Q) and ventilation (V(A)) using fluorescent microspheres in pentobarbital anesthetized and air ventilation dogs in left lateral decubitus posture with synchronous lung inflation. Tidal volume to left and right lung is maintained constant to permit the effect on gas exchange to be examined. The addition of unilateral PEEP to the left lung increased its FRC with no change in left-right blood flow distribution or venous admixture. The overall lung V(A)/Q distribution remained relatively constant with increasing unilateral PEEP. Bilateral PEEP disproportionately increased FRC in the right lung but again produced no significant changes in venous admixture or V(A)/Q distribution. We conclude that the reduced dependent lung blood flow observed without PEEP occurs secondary to a reduction in lung volume. When tidal volume is maintained, unilateral PEEP increases dependent lung volume with little effect of perfusion distribution maintaining gas exchange.     

Evaluation of methodological and biological influences on the collection and composition of exhaled breath condensate

The purpose of this inter-species comparison (calves and pigs) was to identify methodological and biological influences on the collection and composition of exhaled breath condensate (EBC). A total of 352 EBC samples were collected, whilst variables of ventilation were registered in parallel. Partial pressure of carbon dioxide (pCO₂) and pH were analysed in non-degassed EBC samples. The concentration of total protein in EBC was measured colorimetrically. In both species, lung function was evaluated before and after EBC collection. Statistical analyses were performed to study the effect of EBC collection on lung function and to identify the influence of ventilatory variables on the collection and composition of EBC. Collection of EBC did not affect lung function. Despite the volume of EBC collected per unit time being primarily dependent on ventilation per unit time, species-specific conditions during the EBC collection process resulted in different dependences of EBC collection from other variables of ventilation (i.e. maximal airflow during expiration or expired tidal volume kg^-1 body weight). The concentration of protein ml^-1 EBC increased with the expired volume per min and with peak expiratory flow. Although the pCO₂ in fresh EBC was significantly negatively dependent on the duration of collection, comparable pHs (5.6 - 6.2) were measured in EBC of both calves and pigs. The obtained data may help one standardize EBC collection in different species.     

Spatial and temporal heterogeneity of ventilator-associated lung injury after surfactant depletion.

Volutrauma and atelectrauma have been proposed as mechanisms of ventilator-associated lung injury, but few studies have compared their relative importance in mediating lung injury. The objective of our study was to compare the injury produced by stretch (volutrauma) vs. cyclical recruitment (atelectrauma) after surfactant depletion. In saline-lavaged rabbits, we used high tidal volume, low respiratory rate, and low positive end-expiratory pressure to produce stretch injury in nondependent lung regions and cyclical recruitment in dependent lung regions. Tidal changes in shunt fraction were assessed by measuring arterial Po(2) oscillations. After ventilating for times ranging from 0 to 6 h, lungs were excised, sectioned gravitationally, and assessed for regional injury by evaluation of edema formation, chemokine expression, upregulation of inflammatory enzyme activity, and alveolar neutrophil accumulation. Edema formation, lung tissue interleukin-8 expression, and alveolar neutrophil accumulation progressed more rapidly in dependent lung regions, whereas macrophage chemotactic protein-1 expression progressed more rapidly in nondependent lung regions. Temporal and regional heterogeneity of lung injury were substantial. In this surfactant depletion model of acute lung injury, cyclical recruitment produced more injury than stretch.     

Alveolar pressure inhomogeneity during low-frequency oscillation of excised canine lobes

To quantify the inhomogeneity of alveolar pressures (PA) during cyclic changes in lung volume similar to those present during spontaneous breathing, inhomogeneity of PA was measured with an alveolar capsule technique in six excised canine lungs. The lungs were ventilated by a quasi-sinusoidal pump with a constant end-expiratory lung volume and tidal volumes of 10, 20, and 40% of vital capacity at breathing frequencies ranging from 5 to 45 breaths/min. Inhomogeneity of PA was quantified as the sample standard deviation of pressures measured in three capsules. A component of inhomogeneity in phase with flow and a smaller component out of phase with flow were present. The in-phase component increased approximately linearly with flow. The ratio of inhomogeneity to flow was smaller at large tidal volumes and, at the two higher tidal volumes studied, the ratio was greater during inspiration than during expiration. If these data are interpreted in terms of a simple circuit model, this degree of inhomogeneity implies an approximately twofold variation in regional time constants. Despite these considerable differences in time constants, the absolute amount of inhomogeneity as defined by the sample standard deviation of the three PA's was small (maximum 0.57 +/- 0.32 cmH2O at the highest breathing frequency and tidal volume) because airway resistance in the canine lung was small.     

Gas exchange and air flow in the lung of the snake,Pituophis melanoleucus

Summary Gas samples from various regions of the lung were obtained throughout the breathing cycle inPituophis melanoleucus. Changes in CO₂ concentration during the interbreath period differed markedly along the length of the lung. In general, the largest and most rapid increases in CO₂ tension were measured at the cranial end of the vascular lung. Further caudad in the vascular lung, the increase was slower and did not reach mixed venous CO₂ tension before exhalation. In animals exhibiting the lowest breathing frequencies and presumably larger tidal volumes, the region of gas exchange extended into the cranial portion of the air sac. There was little or no change in gas tensions within the remaining caudal regions of the air sac. Measurement of exhaled CO₂ and O₂ tensions at the nares confirmed the longitudinal gradient in gas exchange and also demonstrated the sequential emptying of the lung. Large regional differences in the ratio of blood flow to alveolar volume are probably responsible for the gradients in lung gases.Interpretation of N₂ clearance curves in terms of two freely communicating compartments demonstrated the presence of a ventilation inequality. Consistent with this was the lack of body wall contractions between breaths while animals were resting. However, just prior to and during activity body wall contractions not associated with breathing often occurred and resulted in pressure excursions in the lung of ca. five mm H₂O. In addition, the heart beat results in a pressure change within the lung of ca. 0.2 mmH₂O which may be significant in gas mixing.     

Vertical distribution of specific ventilation in normal supine humans measured by oxygen-enhanced proton MRI

Specific ventilation (SV) is the ratio of fresh gas entering a lung region divided by its end-expiratory volume. To quantify the vertical (gravitationally dependent) gradient of SV in eight healthy supine subjects, we implemented a novel proton magnetic resonance imaging (MRI) method. Oxygen is used as a contrast agent, which in solution changes the longitudinal relaxation time (T1) in lung tissue. Thus alterations in the MR signal resulting from the regional rise in O(2) concentration following a sudden change in inspired O(2) reflect SV-lung units with higher SV reach a new equilibrium faster than those with lower SV. We acquired T1-weighted inversion recovery images of a sagittal slice of the supine right lung with a 1.5-T MRI system. Images were voluntarily respiratory gated at functional residual capacity; 20 images were acquired with the subject breathing air and 20 breathing 100% O(2), and this cycle was repeated five times. Expired tidal volume was measured simultaneously. The SV maps presented an average spatial fractal dimension of 1.13 ± 0.03. There was a vertical gradient in SV of 0.029 ± 0.012 cm(-1), with SV being highest in the dependent lung. Dividing the lung vertically into thirds showed a statistically significant difference in SV, with SV of 0.42 ± 0.14 (mean ± SD), 0.29 ± 0.10, and 0.24 ± 0.08 in the dependent, intermediate, and nondependent regions, respectively (all differences, P < 0.05). This vertical gradient in SV is consistent with the known gravitationally induced deformation of the lung resulting in greater lung expansion in the dependent lung with inspiration. This SV imaging technique can be used to quantify regional SV in the lung with proton MRI.     

Evaluation of methodological and biological influences on the collection and composition of exhaled breath condensate

Abstract

The purpose of this inter-species comparison (calves and pigs) was to identify methodological and biological influences on the collection and composition of exhaled breath condensate (EBC). A total of 352 EBC samples were collected, whilst variables of ventilation were registered in parallel. Partial pressure of carbon dioxide (pCO₂) and pH were analysed in non-degassed EBC samples. The concentration of total protein in EBC was measured colorimetrically. In both species, lung function was evaluated before and after EBC collection. Statistical analyses were performed to study the effect of EBC collection on lung function and to identify the influence of ventilatory variables on the collection and composition of EBC. Collection of EBC did not affect lung function. Despite the volume of EBC collected per unit time being primarily dependent on ventilation per unit time, species-specific conditions during the EBC collection process resulted in different dependences of EBC collection from other variables of ventilation (i.e. maximal airflow during expiration or expired tidal volume kg^?1 body weight). The concentration of protein ml^?1 EBC increased with the expired volume per min and with peak expiratory flow. Although the pCO₂ in fresh EBC was significantly negatively dependent on the duration of collection, comparable pHs (5.6???6.2) were measured in EBC of both calves and pigs. The obtained data may help one standardize EBC collection in different species.     

Regional ventilation in statically and dynamically hyperinflated dogs

Hubmayr, Rolf D., and Susan S. Margulies. Regionalventilation in statically and dynamically hyperinflated dogs.J. Appl. Physiol. 81(4):1815-1821, 1996.Using the parenchymal marker technique innormal anesthetized dogs, we compared the dynamics of regional lungexpansion between two ventilation strategies designed to increase meanthoracic volume. Dynamic hyperinflation (DH) was produced byventilating the lungs at a rate of 50 breaths/min and with a duty cycleof 0.5. Static hyperinflation (SH) was produced throughthe application of extrinsic positive end-expiratory pressure while thelungs were ventilated at a rate of 15 breaths/min and with a duty cycleof 0.15. Regional tidal volume(VT,r), regional functionalresidual volume, and the time delay between regional expansion and the flow signal at the common airway were computed for upto 100 regions/lobe in 5 animals. Ventilation strategy had no effect onthe overall variance of VT,rwithin lobes. Although the VT,rmeasured during SH correlated withVT,r measured during DH, theaverage correlation coefficient was only 0.69. Ventilation rate-relateddifferences in VT,r and regionalfunctional residual capacity varied with the regional time delay inways qualitatively consistent with parallel inhomogeneity of unit timeconstants. However, a large component of frequency-dependent behaviorremains unexplained by established mechanisms. We conclude that DH and SH should not be considered equivalent lung unit recruitmentstrategies.

     

Modification of pulmonary gas mixing by postural changes

Mixing for two gases of markedly different gaseous diffusivity, helium (He) (mol wt = 4) and sulfur hexafluoride (SF6) (mol wt = 146) has been studied by a rebreathing method in different postures. In nine normal subjects duplicate measurements were made in the erect (seated), supine, and lateral decubitus posture, at a constant tidal volume (700 ml) and frequency (1 Hz) starting from functional residual capacity (FRC). Additional measurements were made on four of the subjects, rebreathing seated erect at a volume similar to the relaxed FRC supine and supine at a volume similar to the relaxed FRC seated. In the supine posture the mean breath number to reach 99% equilibrium (n99), was not significantly different for the two gases, 8.9 for He and 9.8 for SF6. There was a difference (P less than 0.01) when erect; n99 (He) = 8.2 and n99 (SF6) = 10.9. The greatest He-SF6 difference (P less than 0.001) was in the lateral decubitus position n99 (He) = 10.1 and n99 (SF6) = 15.9. The mean relaxed FRC as percent of seated was 71% supine and 75% in lateral decubitus posture. Rebreathing seated at a lower volume did not abolish the He-SF6 mixing difference nor did rebreathing at a higher volume when supine induce a He-SF6 mixing difference. Thus the effect of posture on gas mixing cannot be due solely to lung volume and must represent a convective and diffusive dependent change in the distribution of ventilation per unit lung volume.     

Gravity-independent inequality in pulmonary blood flow in humans

Single-photon emission computerized tomography of the lung with 99mTc-labeled human albumin macroaggregates (99mTc-MAA) was used in six healthy subjects to study the three-dimensional distribution of pulmonary blood flow. 99mTc-MAA was injected while the subjects were resting in the supine position and holding their lung volume at normal end expiration. Tomography was performed on each subject from 120 projections of radioactivity in the lungs acquired with a rotating gamma camera. To minimize lung motion artifacts, the subjects were asked to hold their breath at end expiration during the 10-s duration of data acquisition in each projectional angle. Perfusion images of lung slices (11 mm thick) were reconstructed, and the radioactivity within each slice was expressed per unit lung volume of 3.7 X 3.7 X 11 mm. Perfusion images of a midcoronal slice from each subject manifested a concentric pattern of radioactivity that decreased significantly from the center to the periphery, suggesting that blood flow rate per unit lung volume was up to 10 times larger near the central region. This gradient in activity between the center and the periphery of the coronary slices was gravity independent as the subjects were supine. Images of sagittal slices from the middle of the right lung also manifested a similar pattern of concentric gradient in activity, with the vertical distribution (gravity related) almost comparable with the horizontal distribution (gravity independent). These results indicate that pulmonary blood flow in resting supine humans is spatially stratified with a marked central-to-peripheral gradient in all directions. It appears that zone 4 (reduced blood flow) is not a phenomenon limited to the dependent region of the lung as commonly thought but rather is a manifestation of this spatial distribution whereby blood flow is lowest in all peripheral regions of the lung.     

Significance of airway resistance for the pattern of breathing and lung volumes in exercising humans

The effects of increased airway resistance on lung volumes and pattern of breathing were studied in eight subjects performing leg exercise on a cycle ergometer. Airway resistance was changed 1) by increasing the density (D) of the respired gas by a factor of 4.2 and changing the inspired gas from O2 at 1.3 bar to air at 6 bar and 2) by increasing airway flow rates by exposing the subjects to incremental work loads of 0-200 W. Increased gas D caused a slower and deeper respiration at rest and during exercise and, at work loads greater than 120 W, depressed the responses of ventilation and mean inspiratory flow. Raised airway resistance induced by increases in D and/or airway flow rates altered respiratory timing by increasing the ratio of inspiratory time (TI) to total breath duration. Furthermore, analyses of the relationships between tidal volume and TI and between end-inspiratory volume and TI revealed elevation of Hering-Breuer inspiratory volume thresholds. We propose that this elevation, and hence exercise-induced increases of tidal volume, can largely be explained by previous observations that the threshold of the inspiratory off-switch mechanisms depends on central inspiratory activity (cf. C. von Euler, J. Appl. Physiol. 55: 1647-1659, 1983), which in turn increases with airway resistance (Acta Physiol. Scand. 120: 557-565, 1984).     

Quantification of lung surface area using computed tomography

Objective

To refine the CT prediction of emphysema by comparing histology and CT for specific regions of lung. To incorporate both regional lung density measured by CT and cluster analysis of low attenuation areas for comparison with histological measurement of surface area per unit lung volume.

Methods

The histological surface area per unit lung volume was estimated for 140 samples taken from resected lung specimens of fourteen subjects. The region of the lung sampled for histology was located on the pre-operative CT scan; the regional CT median lung density and emphysematous lesion size were calculated using the X-ray attenuation values and a low attenuation cluster analysis. Linear mixed models were used to examine the relationships between histological surface area per unit lung volume and CT measures.

Results

The median CT lung density, low attenuation cluster analysis, and the combination of both were important predictors of surface area per unit lung volume measured by histology (p < 0.0001). Akaike''s information criterion showed the model incorporating both parameters provided the most accurate prediction of emphysema.

Conclusion

Combining CT measures of lung density and emphysematous lesion size provides a more accurate estimate of lung surface area per unit lung volume than either measure alone.