Alveolar Gas Volume Research Articles

Three Alveolar Phenotypes Govern Lung Function in Murine Ventilator-Induced Lung Injury.

Mechanical ventilation is an essential lifesaving therapy in acute respiratory distress syndrome (ARDS) that may cause ventilator-induced lung injury (VILI) through a positive feedback between altered alveolar mechanics, edema, surfactant inactivation, and injury. Although the biophysical forces that cause VILI are well documented, a knowledge gap remains in the quantitative link between altered parenchymal structure (namely alveolar derecruitment and flooding), pulmonary function, and VILI. This information is essential to developing diagnostic criteria and ventilation strategies to reduce VILI and improve ARDS survival. To address this unmet need, we mechanically ventilated mice to cause VILI. Lung structure was measured at three air inflation pressures using design-based stereology, and the mechanical function of the pulmonary system was measured with the forced oscillation technique. Assessment of the pulmonary surfactant included total surfactant, distribution of phospholipid aggregates, and surface tension lowering activity. VILI-induced changes in the surfactant included reduced surface tension lowering activity in the typically functional fraction of large phospholipid aggregates and a significant increase in the pool of surface-inactive small phospholipid aggregates. The dominant alterations in lung structure at low airway pressures were alveolar collapse and flooding. At higher airway pressures, alveolar collapse was mitigated and the flooded alveoli remained filled with proteinaceous edema. The loss of ventilated alveoli resulted in decreased alveolar gas volume and gas-exchange surface area. These data characterize three alveolar phenotypes in murine VILI: flooded and non-recruitable alveoli, unstable alveoli that derecruit at airway pressures below 5 cmH2O, and alveoli with relatively normal structure and function. The fraction of alveoli with each phenotype is reflected in the proportional changes in pulmonary system elastance at positive end expiratory pressures of 0, 3, and 6 cmH2O.

Lobar analysis of collapsibility indices to assess functional lung volumes in COPD patients.

BackgroundWe investigated correlations between lung volume collapsibility indices and pulmonary function test (PFT) results and assessed lobar differences in chronic obstructive pulmonary disease (COPD) patients, using paired inspiratory and expiratory three dimensional (3D) computed tomography (CT) images.MethodsWe retrospectively assessed 28 COPD patients who underwent paired inspiratory and expiratory CT and PFT exams on the same day. A computer-aided diagnostic system calculated total lobar volume and emphysematous lobar volume (ELV). Normal lobar volume (NLV) was determined by subtracting ELV from total lobar volume, both for inspiratory phase (NLVI) and for expiratory phase (NLVE). We also determined lobar collapsibility indices: NLV collapsibility ratio (NLVCR) (%) = (1 − NLVE/NLVI) × 100%. Associations between lobar volumes and PFT results, and collapsibility indices and PFT results were determined by Pearson correlation analysis.ResultsNLVCR values were significantly correlated with PFT results. Forced expiratory volume in 1 second, measured as percent of predicted results (FEV1%P) was significantly correlated with NLVCR values for the lower lobes (P<0.01), whereas this correlation was not significant for the upper lobes (P=0.05). FEV1%P results were also moderately correlated with inspiratory, expiratory ELV (ELVI,E) for the lower lobes (P<0.05). In contrast, the ratio of the diffusion capacity for carbon monoxide to alveolar gas volume, measured as percent of predicted (DLCO/VA%P) results were strongly correlated with ELVI for the upper lobes (P<0.001), whereas this correlation with NLVCR values was weaker for upper lobes (P<0.01) and was not significant for the lower lobes (P=0.26).ConclusionFEV1%P results were correlated with NLV collapsibility indices for lower lobes, whereas DLCO/VA%P results were correlated with NLV collapsibility indices and ELV for upper lobes. Thus, evaluating lobar NLV collapsibility might be useful for estimating pulmonary function in COPD patients.

The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse.

Inert-gas washout measurements using oxygen, in the lungs of small animals, are complicated by the continuous process of oxygen consumption (V̇o2). The multiple-breath nitrogen washout (MBNW) technique uses the alveolar slope to determine measures of ventilation inhomogeneity in the acinar (Sacin) and conducting (Scond) airway regions, as well as overall inhomogeneity, as determined by the lung clearance index (LCI). We hypothesized that measured ventilation inhomogeneity in the mouse lung while it is alive is in fact an artifact due to the high V̇o2 in proportion to alveolar gas volume (Va), and not ventilation inhomogeneity per se. In seven male C57BL/6 mice, MBNW was performed alive and postmortem to derive measures with and without the effect of gas exchange, respectively. These results were compared with those obtained from an asymmetric multibranch point mathematical model of the mouse lung. There was no statistical difference in Sacin and LCI between alive and postmortem results (Sacin alive = 0.311 ± 0.043 ml(-1) and Sacin postmortem = 0.338 ± 0.032 ml(-1), LCI alive = 7.0 ± 0.1 and LCI postmortem = 7.0 ± 0.1). However, there was a significant decrease in Scond from 0.086 ± 0.005 ml(-1) alive to 0.006 ± 0.002 ml(-1) postmortem (P < 0.01). Model simulations replicated these results. Furthermore, in the model, as V̇o2 increased, so did the alveolar slope. These findings suggests that the MBNW measurement of Scond in the mouse lung is confounded by the effect of gas exchange, a result of the high V̇o2-to-Va ratio in this small animal, and not due to inhomogeneity within the airways.

How does a hopping kangaroo breathe?

We developed a model to demonstrate how a hopping kangaroo breathes. Interestingly, a kangaroo uses less energy to breathe while hopping than while standing still. This occurs, in part, because rather than using muscle power to move air into and out of the lungs, air is pulled into (inspiration) and pushed out of (expiration) the lungs as the abdominal organs "flop" within the kangaroo's body. Specifically, as the kangaroo hops upward, the abdominal organs lag behind, and the insertion of the diaphragm is pulled toward its origin, flattening the dome and increasing the vertical dimension of the thoracic cavity (the thoracic cavity and lungs enlarge). Increasing the volume of the thoracic cavity reduces alveolar pressure below atmospheric pressure (barometric pressure), and air moves into the alveoli by bulk flow. In contrast, the impact of the organs against the diaphragm at each landing causes expiration. Specifically, upon landing, the abdominal organs flop into the diaphragm, causing it to return to its dome shape and decreasing the vertical dimension of the thoracic cavity. This compresses the alveolar gas volume and elevates alveolar pressure above barometric pressure, so air is expelled. To demonstrate this phenomenon, the plunger of a syringe model of the respiratory system was inserted through a compression spring. Holding the syringe and pressing the plunger firmly against a hard surface expels air from the lungs (the balloon within the syringe deflates) and compresses the spring. This models the kangaroo landing after a hop forward. Subsequently, the compression spring provides the energy for the "kangaroo" to "hop" forward upon the release of the syringe, and air enters the lungs (the balloon within the syringe inflates). The model accurately reflects how a hopping kangaroo breathes. A model was chosen to demonstrate this phenomenon because models engage and inspire students as well as significantly enhance student understanding.

The Impact of Various Anthropometric Measurements of Obesity on Pulmonary Function in Candidates for Surgery

Obesity has proven to be associated with respiratory symptoms and impaired pulmonary function, which could increase the incidence of postoperative complications after bariatric surgery. However, the component of obesity that has the most influence on pulmonary function has not been identified, especially in Asian-Pacific populations. This cross-sectional study enrolled obese Chinese patients >or=18 years of age with a body mass index (BMI) >32 kg/m(2), who were being evaluated for bariatric surgery. All patients performed pulmonary function test, and the results were analyzed according to various anthropometric measurements. Multiple-regression analyses were also conducted and adjusted for age, sex, and smoking history to determine the factors that impaired the pulmonary function of the obese patients. A total of 150 consecutive patients were enrolled from July 2007 to August 2008. We found that body weight, BMI, waist circumference (WC), hip circumference, and waist-to-height ratio but not waist-to-hip ratio had a significant correlation with decreased forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), total lung capacity (TLC), vital capacity (VC), and increased diffusing capacity of the lung for carbon monoxide to alveolar gas volume. After multiple linear regression analysis, only WC was associated with reductions in FEV1, FVC, TLC, and VC. Obesity is associated with a restrictive pattern of impaired pulmonary function in various anthropometric parameters measured in obese Chinese adults in Taiwan. Among these parameters, WC had the greatest impact on pulmonary function, which could also implicate the rate of postoperative complication and the need of more intensive care after bariatric surgery.

Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism

The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 ± 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 ± 8.64 to 39.14 ± 6.77 mmHg) and alveolar air (from 92.97 ± 2.14 to 63.91 ± 8.27 mmHg). The effective alveolar ventilation exhibited a significant reduction (from 199.62 ± 42.01 to 84.34 ± 44.13) consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio) also presented a significant reduction after embolization (from 0.96 ± 0.34 to 0.33 ± 0.17 fraction). The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 ± 1.71 to 60.76 ± 6.62 mmHg), but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 ± 1.22 to 23.15 ± 8.24 mmHg). Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 ± 1.36 to 37.61 ± 12.79 mmHg), as also did the calculated alveolar (from 56.38 ± 22.47 to 178.09 ± 37.46 mL) and physiological (from 0.37 ± 0.05 to 0.75 ± 0.10 fraction) dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation redistribution induced by hypocapnic bronchoconstriction.

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The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 +/- 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 +/- 8.64 to 39.14 +/- 6.77 mmHg) and alveolar air (from 92.97 +/- 2.14 to 63.91 +/- 8.27 mmHg). The effective alveolar ventilation exhibited a significant reduction (from 199.62 +/- 42.01 to 84.34 +/- 44.13) consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio) also presented a significant reduction after embolization (from 0.96 +/- 0.34 to 0.33 +/- 0.17 fraction). The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 +/- 1.71 to 60.76 +/- 6.62 mmHg), but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 +/- 1.22 to 23.15 +/- 8.24 mmHg). Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 +/- 1.36 to 37.61 +/- 12.79 mmHg), as also did the calculated alveolar (from 56.38 +/- 22.47 to 178.09 +/- 37.46 mL) and physiological (from 0.37 +/- 0.05 to 0.75 +/- 0.10 fraction) dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation redistribution induced by hypocapnic bronchoconstriction.

Topographical distribution of pulmonary perfusion and ventilation, assessed by PET in supine and prone humans.

Using positron emission tomography (PET) and intravenously injected (13)N(2), we assessed the topographical distribution of pulmonary perfusion (Q) and ventilation (V) in six healthy, spontaneously breathing subjects in the supine and prone position. In this technique, the intrapulmonary distribution of (13)N(2), measured during a short apnea, is proportional to regional Q. After resumption of breathing, regional specific alveolar V (sVA, ventilation per unit of alveolar gas volume) can be calculated from the tracer washout rate. The PET scanner imaged 15 contiguous, 6-mm-thick, slices of lung. Vertical gradients of Q and sVA were computed by linear regression, and spatial heterogeneity was assessed from the squared coefficient of variation (CV(2)). Both CV and CV were corrected for the estimated contribution of random imaging noise. We found that 1) both Q and V had vertical gradients favoring dependent lung regions, 2) vertical gradients were similar in the supine and prone position and explained, on average, 24% of Q heterogeneity and 8% of V heterogeneity, 3) CV was similar in the supine and prone position, and 4) CV was lower in the prone position. We conclude that, in recumbent, spontaneously breathing humans, 1) vertical gradients favoring dependent lung regions explain a significant fraction of heterogeneity, especially of Q, and 2) although Q does not seem to be systematically more homogeneous in the prone position, differences in individual behaviors may make the prone position advantageous, in terms of V-to-Q matching, in selected subjects.

Interrelationships between regional blood flow, blood volume, and ventilation in supine humans

Positron emission tomography was used to measure alveolar gas volume, pulmonary blood volume (VB), regional alveolar ventilation (VA), and the regional ventilation-to-perfusion ratio (VA/Q) in a transaxial slice at midheart level in eight supine subjects and one prone normal subject during quiet breathing. These relationships allow regional blood flow (Q) to be calculated as VA/(VA/Q). No significant differences between right and left lung were found. Within the volume studied, which excluded the peripheral 2 cm of the lung, there was an exponential increase in Q by 11%/cm from 1.2 ml.min-1.cm-3 in the upper (ventral) to 3.5 ml.min-1.cm-3 in the lower (dorsal) lung regions, explaining 61% of the total variation within groups, whereas the horizontal gradient only explained 7% (right lung; supine subjects). Similar gravitational gradients were found in the single prone subject. VA and Q were well matched except at the dorsal lung thoracic border where low values of VA/Q due to a reduction in ventilation were occasionally found even in these normal subjects. VB and Q were reasonably well matched, implying that variations in vascular transit time due to gravity are kept to a minimum. The coefficient of local variation of peripheral vascular transit times (VB/Q) (33%) was, therefore, less than would have been expected if VB and Q were uncorrelated (57%).

Measurement of alveolar gas volume by ambient pressure changes in isolated lungs.

Alveolar gas volume (AGV) may be measured in humans (Peslin et al., J. Appl. Physiol. 62: 359-363, 1987) by applying very slow sinusoidal variations of ambient pressure (delta Pam) around the body and studying the relationship between delta Pam and the resulting gas displacement at the mouth (delta Vaw): AGVapc = (PB.delta Vaw)/(delta Pam.cos phi), where AGVapc is AGV measured by ambient pressure changes, PB is barometric minus alveolar water vapor pressure, and phi is the phase angle between Pam and Vaw. The applicability of this method to excised lungs at various transpulmonary pressures was assessed in six rabbit lungs and three dog lobes by reference to AGV measurements by He dilution (AGVdil) and by a volumetric method (AGVvol). Except in one instance, AGVapc did not change significantly when the frequency of delta Pam was varied from 0.02 to 0.2 Hz. AGVapc was highly correlated (P less than 0.001) to both AGVdil and AGVvol. It did not differ significantly from AGVdil (81.4 +/- 50.6 vs. 80.2 +/- 44.2 ml) and was only marginally higher than AGVvol (64.6 +/- 26.9 vs. 62.4 +/- 24.4 ml, P less than 0.05). We conclude that the method usually provides accurate results in excised lung preparations. Its main advantages are that it does not require manipulating the lung or changing its volume and that the measurement takes less than 1 min.

Assessment of Time-Volume and Flow-Volume Components of Forced Vital Capacity: Measurement with Spirometry, Body Plethysmography and Respiratory Inductive Plethysmography in Nonsmokers and Smokers

The purpose of this investigation was to assess the effectiveness of the time-volume and flow-volume components of the forced vital capacity measured by simultaneous spirometry, respiratory inductive plethysmography, and body plethysmography in detecting small airway disease. Spirometry measured the exit of gas from the lungs, whereas body plethysmography measured both the exit of gas and alveolar gas compression. Respiratory inductive plethysmography, which reflected change in thoracic volume, provided semi-quantitative data f both gas exit and alveolar gas compression which generally lay between spirometry and body plethysmography. In nine nonsmokers and 12 smokers (six with small airway disease as defined by abnormal closing volumes and alveolar uniformity), analysis of forced vital capacity revealed that the only test which differentiated nonsmokers from smokers was the higher spirometric estimation of maximum expiratory flow measured at 25 percent VC in nonsmokers. Combining flow measure at the mouth with volume referenced to change in alveolar gas volume as measured by body or respiratory inductive plethysmography did not differentiate nonsmokers from smokers. Moment analysis performed of forced vital capacity with all of the three devices did not distinguish nonsmokers from smokers. The data in this study and a review of other investigations indicate that the time-volume and flow-volume components of the forced vital capacity on air breathing are not very sensitive in detecting early lung disease in smokers.

Assessment of Density Dependent Flow-Volume Parameters in Nonsmokers and Smokers: Measurement with Spirometry, Body Plethysmography and Respiratory Inductive Plethysmography

The purpose of this investigation was to assess the density-dependent flow-volume components of the forced vital capacity using simultaneous spirometry, respiratory inductive plethysmography, and body plethysmography in the detection of small airway disease. The forced vital capacity was measured during air, helium-oxygen and sulfur-hexafluoride breathing to provide a range of gas density influences. Combining flow measured at the mouth with volume referenced to change in alveolar gas volume as measured by body or respiratory inductive plethysmography during helium-oxygen breathing accentuated the differences between nonsmokers and smokers because of the variable degree of alveolar gas compression occurring over the second half of FVC. The volume of isoflow obtained when comparing the helium and oxygen mixture to air also effectively separated nonsmokers from smokers. The utilization of the high density gas mixture, sulfur hexafluoride-oxygen during the FVC maneuver did not provide useful diagnostic information. Therefore, density-dependent flow-volume information using helium as a test gas alone or compared to air with a variety of analyses is a good approach to detection of early lung disease in smokers.

LUNG TISSUE VOLUME ESTIMATE BY SIMULTANEOUS RADIOGRAPHIC AND HELIUM DILUTION METHODS

Lung tissue volume measurement adds quantitative information to the diagnosis and assessment of the response to therapy in patients with increased extravascular lung water. Indicator-dilution and acetylene rebreathing measurements are difficult and limited to research investigations. We reasoned that total lung tissue (lung tissue, blood and extravascular water) volume (VTT) could be estimated using the difference between radiographic displacement volume of the thorax (RDVT and alveolar gas volume (VA) by helium rebreathing. Ten healthy subjects underwent simultaneous RDVT and VA determinations using upright posteroanterior (PA) and lateral (LAT) chest radiographs and helium rebreathing. RDVT was measured from radiographs using a computerized modification of the Barnhard method (Barrett WA et al: 1976 AARD 113: 239–244). VA was obtained simultaneously following the PA and LAT radiographic exposures. The average VTT at functional residual capacity (FRC) was 730 + 75 ml which includes capillary blood, most of the major arterial and venous blood in the pulmonary circulation, extra-vascular water and lung tissue (dry weight). This estimate is greater than those measured with acetylene (approximately 630 ml) (Farney FJ, Morris AH, Gardner RM, Armstrong JD, J Appl Physiol 1977 43: 246–253) but falls below the expected by 135 ml (lung dry weight 160 ml, lung blood volume 320 ml and extravascular water 385 ml). The agreement of radiographic estimates of total tissue volume with data obtained by other methods is promising and may provide accurate measurements of VTT in selected patients with uncomplicated heart failure or diffuse interstitial processes.

The influence of the haldane effect on alveolar CO2 tension equilibrated with mixed venous blood in man.

When blood in the pulmonary capillary is oxygenated in hypercapnic air, PCO2 in the red cell has been thought to exceed alveolar PCO2 due to the Haldane effect, inducing outward CO2 diffusion. As long as the inward CO2 diffusion and, consequently, HCO3- formation are prevented in the red cell, the CO2 gain in plasma is reduced down to the level predicted from a CO2 dissociation curve of separated plasma. Therefore, if the direction of the CO2 diffusion is not reversed during the contact time, the virtual venous PCO2 (PEq), where the CO2 loss due to the Haldane effect is balanced with the gain due to the venoalveolar PCO2 gradient, becomes higher than the oxygenated venous PCO2 in proportion to the CO2 difference between the true and separated plasma. In order to verify the validity of the above assumption, the PEq value was measured in normo- and hypercapnia by using the Defares' extrapolation method in six normal subjects. The results obtained revealed that the PEq estimated in hypercapnia was obviously higher than that in normocapnia. The above difference was significantly greater in normoxia than in hypoxia. Furthermore, it agreed fairly well with the theoretical difference presumed by taking the difference in CO2 content between separated and true plasma and the R. Q. effect on the alveolar gas volume into account, suggesting that the inward CO2 diffusion following the oxygenation reaction could be disregarded in normoxic hypercapnia.

The CO single breath transfer factor of the lung. A reliable clinical parameter in valvular heart disease.

The CO single breath transfer factor of the lung expressed per unit of alveolar gas volume during breath-holding, Tv, and its component factors Dmv and Vcv have been determined in 46 patients suffering from valvular heart disease. It has been shown that Tv cannot be correctly interpreted, unless the values of Dmv and Vcv are known. The results of measurements of gas transfer using this method offer a reliable guide for establishing the efficacy of the cardiac pump, and for following up the effect of therapy in valvular heart disease.

A METHOD OF ANALYSIS OF THE PULMONARY GAS EXCHANGE SYSTEM

This method of system analysis is based on O2 and CO2 concentration curves obtained simultaneously from expired air during constant flow expiration. First, theoretical equations for alveolar O2 and CO2 curves were derived by using a simple gas exchange model. By substituting them with the measured data on alveolar gas concentrations and volume, such parameters as O2 uptake VO2, pulmonary blood flow Q and venous PCO2 were estimated. Expired air was continuously analyzed by means of a glow discharge gas analyzer and the alveolar gas volume was measured immediately after the gas analysis using a body plethysmograph. The estimated Q value showed a dispersion of about 14% average standard deviation in each subject, but other parameters showed no large variation. The average Q values of several measurements, however, corresponded with those obtained by an acetylene inhalation method. The VO2 also corresponded well with that measured by spirometry. This coinciding data seemed to reveal that the model was reasonable for the analysis. CO2 output, by virtue of the Haldane effect, was examined through the analyses in both normoxia and hypoxia in 9 normal subjects. No significant effect was observed.