Effect of lung volume on ventilation distribution

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Moment analysis of multibreath nitrogen washout in young children

The purpose of this study was to determine whether on-line computerized moment analysis of multibreath N2 washout (MBNW) could be used as a method of estimating lung function in children too young to cooperate with routine pulmonary function testing. The limits of normal variability were determined from results obtained from duplicate studies performed on 36 healthy children ages 3-6 yr. Five healthy adults were studied for comparison. Test sensitivity was estimated by comparing the results in the healthy group to those of 10 age-matched children with cystic fibrosis (CF). Outcome variables of interest included functional residual capacity, the first-to-zeroth moment ratio (M1/M0), the second-to-zeroth moment ratio (M2/M0), and the lung clearance index. Test precision in the healthy group was high with the intrasubject coefficient of variation for all variables being less than 10%. There was no difference in mean within- or among-subject variability between the healthy children and the older, theoretically more cooperative, healthy adults. Mean M1/M0 and M2/M0 were both higher in CF than in the healthy group, 2.69 vs. 2.32 and 13.04 vs. 9.31, respectively (P less than 0.001). Moment ratios in CF showed good negative correlations with Shwachman scores; thus those CF patients with the most advanced lung disease had the highest moment ratios and vice versa. Moment analysis of MBNW has promise as a means of quantifying lung function in young children, since the method is noninvasive, low in inherent variability, requires only quiet breathing, and has the sensitivity required to detect rather mild ventilation inhomogeneity.     

Effect of airway closure on ventilation distribution

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80-90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502-2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.     

Effect of breath holding on ventilation maldistribution during tidal breathing in normal subjects

To test the hypothesis that during the course of a multiple-breath N2 washout (MBNW) diffusion-dependent ventilation maldistribution is more apparent in the early breaths, whereas convection-dependent maldistribution predominates in the later breaths, we performed MBNW with 0-, 1-, and 4-s end-inspiratory breath holds (BH0, BH1, BH4, respectively) in five normal subjects. Each subject breathed with a constant tidal volume of 1 liter, at 10-12 breaths/min and at constant flow rates. For each breath we computed the slope of the alveolar plateau normalized by the mean expired N2 concentration (Sn), the Bohr dead space (VDB), and an index analogous to the Fowler dead space (V50). In all five subjects, Sn, VDB, and V50 decreased with breath holding, indicating diffusion dependence of these indexes. Over the first five breaths the rate of increase of Sn as a function of cumulative expired volume (delta Sn/delta sigma VE) decreased by 29 and 54% during BH1 and BH4, respectively, compared with BH0. In contrast, from breath 5 to the end of the washout there was no significant change in delta Sn/delta sigma VE during BH1 and BH4 compared with BH0. Our results provide further experimental support for the hypothesis that the increase of Sn as a function of cumulative expired volume after the fifth breath constitutes a diffusion-independent index of ventilation inhomogeneity. It therefore reflects alveolar gas inequalities among larger units.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of expiratory threshold loading during steady-state exercise.

Increases in functional residual capacity (FRC) decrease inspiratory muscle efficiency; the present experiments were designed to determine the effect of FRC change on the ventilatory response to exercise. Six well-trained adults were exposed to expiratory threshold loads (ETL) ranging from 5 to 40 cmH2O during steady-state exercise on a bicycle ergometer at 40-95% VO2max. Inspiratory capacity (IC) was measured and changes of IC interpreted as changes of FRC. ETL did not consistently limit exercise performance. At heavy work (greater than 92% VO2max) minute ventilation decreased with increasing ETL; at moderate work (less than 58% VO2max) it did not. Decreases in ventilation were due to decreases in respiratory frequency with prolongation of the duration of expiration being the most consistent change in breathing pattern. At moderate work levels, FRC increased with ETL; at maximum work it did not. Changes in FRC were dictated by constancy of tidal volume and a fixed maximum end-inspiratory volume of 80-90% of the inspiratory capacity. When tidal volume was such that end-inspiratory volume was less than this value, FRC increased with ETL. Mouth pressure measured during the first 0-1 s of inspiratory effort against an occluded airway (P0-1) was increased by ETL equals 30 cmH2O, in spite of the fact that ventilation was decreased. We concluded that changes in FRC due to ETL had no effect on the ventilatory response to exercise and that changes in P0-1 induced by ETL did not reflect changes of inspiratory drive so much as changes of the pattern of inspiration.     

Does increased baseline ventilation heterogeneity following chest wall strapping predispose to airway hyperresponsiveness?

Baseline ventilation heterogeneity is associated with airway hyperresponsiveness (AHR) in asthma; however, it is unknown whether increased baseline ventilation heterogeneity leads to AHR or both are independent effects of similar disease pathophysiology. Reducing functional residual capacity (FRC) in healthy subjects increases baseline ventilation heterogeneity and airway responsiveness, but the relationship between the two is unclear. The aim was to determine whether an increase in baseline ventilation heterogeneity due to a reduction in FRC correlated with the increase in response to methacholine. In 13 healthy male subjects, ventilation heterogeneity was measured by multiple-breath N(2) washout before a cumulative high-dose (0.79-200 μmol) methacholine challenge. On a separate day, the protocol was performed with chest wall strapping (CWS) to reduce FRC. Indexes of ventilation heterogeneity in the convection-dependent (Scond) and diffusion-convection-dependent (Sacin) airways were calculated from the multiple-breath N(2) washout. CWS decreased FRC by 15.6 ± 2.7% (P < 0.0001). CWS increased the percent fall in forced expiratory volume in 1 s during bronchial challenge (P = 0.006), and the magnitude of this effect was independently determined by the effect of CWS on Sacin and FRC (r(adj)(2) = 0.55, P = 0.02). This suggests that changes in baseline ventilation heterogeneity in healthy subjects are sufficient to increase airway responsiveness, independent of the presence of disease pathology.     

Tracheal smooth muscle mechanics in vivo

We applied the technique of sonomicrometry to directly measure length changes of the trachealis muscle in vivo. Pairs of small 1-mm piezoelectric transducers were placed in parallel with the muscle fibers in the posterior tracheal wall in seven anesthetized dogs. Length changes were recorded during mechanical ventilation and during complete pressure-volume curves of the lung. The trachealis muscle showed spontaneous fluctuations in base-line length that disappeared after vagotomy. Before vagotomy passive pressure-length curves showed marked hysteresis and length changed by 18.5 +/- 13.2% (SD) resting length at functional residual capacity (LFRC) from FRC to total lung capacity (TLC) and by 28.2 +/- 16.2% LFRC from FRC to residual volume (RV). After vagotomy hysteresis decreased considerably and length now changed by 10.4 +/- 3.7% LFRC from FRC to TLC and by 32.5 +/- 14.6% LFRC from FRC to RV. Bilateral supramaximal vagal stimulation produced a mean maximal active shortening of 28.8 +/- 14.2% resting length at any lung volume (LR) and shortening decreased at lengths above FRC. The mean maximal velocity of shortening was 4.2 +/- 3.9% LR.S-1. We conclude that sonomicrometry may be used to record smooth muscle length in vivo. Vagal tone strongly influences passive length change. In vivo active shortening and velocity of shortening are less than in vitro, implying that there are significant loads impeding shortening in vivo.     

Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.     

Respiratory impedance and multibreath N2 washout in healthy, asthmatic, and cystic fibrosis subjects

We measured forced expiratory volume in 1 s (FEV1), respiratory impedance (Zrs) from 4 to 60 Hz, and a multibreath N2 washout (MBNW) in 6 normal, 10 asthmatic, and 5 cystic fibrosis (CF) subjects. The MBNW were characterized by the mean dilution number (MDN) derived by a moment analysis. The Zrs spectra were characterized by the minimum resistance (Rmin), the drop in resistance (Rdrop) from 4 Hz to Rmin, and the first resonance frequency (Fr1). Measurements were repeated after bronchodilation in three normal and all asthmatic subjects. Before bronchodilation, six of the asthmatic subjects showed close to normal FEV1. The Zrs in the normal subjects showed low Rmin (1.9 +/- 0.7 cmH2O.l-1.s), Rdrop (0.4 +/- 0.4), and Fr1 (10 +/- 2 Hz). Four of the mildly obstructed asthmatic subjects had normal Zrs but elevated MDNs (i.e., abnormal ventilation distribution). The other six asthmatic subjects had significantly elevated Rmin (4.1 +/- 0.8), Rdrop (6.3 +/- 5.8), and Fr1 (34 +/- 0.4 Hz) and elevated MDNs. The CF patients had elevated Zrs features and MDNs. After bronchodilation, no changes in FEV1, MDN, or Zrs occurred in the normal subjects. All asthmatic subjects showed increased FEV1 and decreased MDN, but the Zrs was unaltered in the four asthmatic subjects whose base-line Zrs was normal. For the other six asthmatic subjects, there were large decreases in the Rmin, Rdrop, and Fr1. Finally, there was a poor correlation between the MDN and the Zrs features but high correlation between the Zrs features alone. These results imply that significant nonuniform peripheral airway obstruction can exist such that ventilation distribution is abnormal but Zrs from 4 to 60 Hz is not. Abnormalities in Zrs from 4 to 60 Hz occur only after significant overall obstruction in the peripheral and more central airways. Combining Zrs and the MBNW may permit us to infer whether the disease is predominantly in the lung periphery or in the more central airways.     

Partial forced expiratory flow-volume curves in young children during ketamine anesthesia

Maximal flows at functional residual capacity (VmaxFRC) from partial forced expiratory flow-volume (PEFV) curves were obtained in 14 normal preschool children (8 boys, 6 girls) of average age 44 mo, under general anesthesia before elective surgery. PEFV curves were generated from end inspiration by rapid compression of the chest wall with an inflatable jacket. VmaxFRC, expressed in milliliter per second, correlated linearly with height, weight, age, and FRC in milliliter and milliliters per kilogram. The best correlation of VmaxFRC (ml/s) was to height to the power of 2.47, which agrees with the results predicted by wave-speed theory. Mean FRC-corrected VmaxFRC was 2.42 +/- 0.50 (SD) FRC's/s with no significant difference between boys (2.35 FRC's/s) and girls (2.51 FRC's/s). There was no correlation between lung-size corrected VmaxFRC and height, weight, or age, but it tended to decrease with increasing FRC. The intersubject variability for VmaxFRC was reduced by normalizing for FRC, and was significantly better than that reported for awake children. This can be attributed to the greater control over volume history and more reliable maximal flow generation during anesthesia. The intrasubject coefficient of variation (CV) for VmaxFRC was 12.2%, and the intersubject CV was 20.0%. The difference may represent the variability due to dysanapsis. It is concluded that dysanapsis is not a prominent factor in children of this age group. In addition, the similarity of the regression equation for VmaxFRC vs. height to that of FRC vs. height supports the concept of equidimensional growth of the airways and lung parenchyma.     

Effects of deep inhalation in asthma: relative airway and parenchymal hysteresis

Asthmatic subjects were screened for the effects or volume history on the degree of induced airway obstruction with methacholine by comparing isovolumic maximal expiratory flows (Vmax) from partial expiratory flow-volume curves (P) begun near functional residual capacity (FRC) followed by maximal expiratory flow-volume (M) maneuvers begun from total lung capacity (TLC). The isovolumic Vmax values from M and P maneuvers defined two groups: one had a high M/P ratio (high group), indicating a large degree of reversal with deep inhalation, another had a low M/P ratio (low group), indicating minimal reversal. No differences were found between groups. A more complete study was later performed in which we measured specific airway conductance (sGaw) and anatomical dead space (VD) as indices of airway size and hysteresis before and after deep inhalation. The area of quasi-static transpulmonary pressure (Ptp) volume (V) curves from FRC to TLC and back to FRC was measured as an index of parenchymal hysteresis. At base line both groups showed a decrease in both sGaw and VD after a deep inhalation (DI). After constriction neither group changed VD after DI, whereas sGaw increased significantly in the high group after DI. This suggests that dilation of airways with DI occurred peripheral to those contributing to VD in the high group. The areas of the Ptp-V curves were equal at base line; yet the increase in areas with constriction in the low group was much greater.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lung Volume,Breathing Pattern and Ventilation Inhomogeneity in Preterm and Term Infants

Background

Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques.

Methodology/Principal Findings

We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t _PTEF/t _E) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity.

Conclusions

Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process.     

Inter- and intraregional ventilation inhomogeneity in hypergravity and after pressurization of an anti-G suit.

This study assessed the effects of increased gravity in the head-to-foot direction (+G(z)) and anti-G suit (AGS) pressurization on functional residual capacity (FRC), the volume of trapped gas (V(TG)), and ventilation distribution by using inert- gas washout. Normalized phase III slope (Sn(III)) analysis was used to determine the effects on inter- and intraregional ventilation inhomogeneity. Twelve men performed multiple-breath washouts of SF(6) and He in a human centrifuge at +1 to +3 G(z) wearing an AGS pressurized to 0, 6, or 12 kPa. Hypergravity produced moderately increased FRC, V(TG), and overall and inter- and intraregional inhomogeneities. In normogravity, AGS pressurization resulted in reduced FRC and increased V(TG), overall, and inter- and intraregional inhomogeneities. Inflation of the AGS to 12 kPa at +3 G(z) reduced FRC markedly and caused marked gas trapping and intraregional inhomogeneity, whereas interregional inhomogeneity decreased. In conclusion, increased +G(z) impairs ventilation distribution not only between widely separated lung regions, but also within small lung units. Pressurizing an AGS in hypergravity causes extensive gas trapping accompanied by reduced interregional inhomogeneity and, apparently, results in greater intraregional inhomogeneity.     

Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized 99mTc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.     

Changes in Positive End-Expiratory Pressure Alter the Distribution of Ventilation within the Lung Immediately after Birth in Newborn Rabbits

Current recommendations suggest the use of positive end-expiratory pressures (PEEP) to assist very preterm infants to develop a functional residual capacity (FRC) and establish gas exchange at birth. However, maintaining a consistent PEEP is difficult and so the lungs are exposed to changing distending pressures after birth, which can affect respiratory function. Our aim was to determine how changing PEEP levels alters the distribution of ventilation within the lung. Preterm rabbit pups (28 days gestation) were delivered and mechanically ventilated with one of three strategies, whereby PEEP was changed in sequence; 0-5-10-5-0 cmH₂O, 5-10-0-5-0 cmH₂O or 10-5-0-10-0 cmH₂O. Phase contrast X-ray imaging was used to analyse the distribution of ventilation in the upper left (UL), upper right (UR), lower left (LL) and lower right (LR) quadrants of the lung. Initiating ventilation with 10PEEP resulted in a uniform increase in FRC throughout the lung whereas initiating ventilation with 5PEEP or 0PEEP preferentially aerated the UR than both lower quadrants (p<0.05). Consequently, the relative distribution of incoming V_T was preferentially directed into the lower lobes at low PEEP, primarily due to the loss of FRC in those lobes. Following ventilation at 10PEEP, the distribution of air at end-inflation was uniform across all quadrants and remained so regardless of the PEEP level. Uniform distribution of ventilation can be achieved by initiating ventilation with a high PEEP. After the lungs have aerated, small and stepped reductions in PEEP result in more uniform changes in ventilation.     

Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates.

A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas.     

Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans

We examined the effects of lung volume on the bronchoconstriction induced by inhaled aerosolized methacholine (MCh) in seven normal subjects. We constructed dose-response curves to MCh, using measurements of inspiratory pulmonary resistance (RL) during tidal breathing at functional residual capacity (FRC) and after a change in end-expiratory lung volume (EEV) to either FRC -0.5 liter (n = 5) or FRC +0.5 liter (n = 2). Aerosols of MCh were generated using a nebulizer with an output of 0.12 ml/min and administered for 2 min in progressively doubling concentrations from 1 to 256 mg/ml. After MCh, RL rose from a base-line value of 2.1 +/- 0.3 cmH2O. 1-1 X s (mean +/- SE; n = 7) to a maximum of 13.9 +/- 1.8. In five of the seven subjects a plateau response to MCh was obtained at FRC. There was no correlation between the concentration of MCh required to double RL and the maximum value of RL. The dose-response relationship to MCh was markedly altered by changing lung volume. The bronchoconstrictor response was enhanced at FRC - 0.5 liter; RL reached a maximum of 39.0 +/- 4.0 cmH2O X 1-1 X s. Conversely, at FRC + 0.5 liter the maximum value of RL was reduced in both subjects from 8.2 and 16.6 to 6.0 and 7.7 cmH2O X 1-1 X s, respectively. We conclude that lung volume is a major determinant of the bronchoconstrictor response to MCh in normal subjects. We suggest that changes in lung volume act to alter the forces of interdependence between airways and parenchyma that oppose airway smooth muscle contraction.     

Respiratory load compensation in chronic airway obstruction

To assess respiratory neuromuscular function and load compensating ability in patients with chronic airway obstruction (CAO), we studied eight stable patients with irreversible airway obstruction during hyperoxic CO2 rebreathing with and without a 17 cmH2O X l-1 X s flow-resistive inspiratory load (IRL). Minute ventilation (VE), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi) were monitored. Pdi and EMGdi were obtained via a single gastroesophageal catheter with EMGdi being quantitated as the average rate of rise of inspiratory (moving average) activity. Based on the effects of IRL on the Pdi response to CO2 [delta Pdi/delta arterial CO2 tension (PaCO2)] and the change in Pdi for a given change in EMGdi (delta Pdi/delta EMGdi) during rebreathing, two groups could be clearly identified. Four patients (group A) were able to increase delta Pdi/delta PaCO2 and delta Pdi/delta EMGdi, whereas in the other four (group B) the IRL responses decreased. All group B patients were hyperinflated having significantly greater functional residual capacity (FRC) and residual volume than group A. In addition the IRL induced percent change in delta Pdi/delta PaCO2, and delta VE/delta PaCO2 was negatively correlated with lung volume so that in the hyperinflated group B the higher the FRC the greater was the decrease in Pdi response due to IRL. In both groups the greater the FRC the greater was the decrease in the ventilatory response to loading. Patients with CAO, even with severe airways obstruction, can effect load compensation by increasing diaphragmatic force output, but the presence of increased lung volume with the associated shortened diaphragm prevents such load compensation.     

Model simulations of gas mixing and ventilation distribution in the human lung

A new lung model that incorporates intra-acinar diffusion- and convection-dependent inhomogeneities (DCDI) and interregional and intraregional convection-dependent inhomogeneities (CDI) is described. The model is divided into two regions, each containing two subunits. Each of the four subunits in the model consists of a multi-branch-point structure, based on the anatomic data from Haefeli-Bleuer and Weibel (Anat. Record 220: 401-414, 1988). The subunit turnover (TO), i.e., the ratio of subunit tidal to resting volume, and the flow sequences (FS) between the subunits are used as model parameters. The model simulates the normalized alveolar slope (Sn), Fowler and Bohr dead space (VDF and VDB), and alveolar mixing efficiency (AME) as a function of breath number (n) during a multiple-breath N2 washout (MBNW). For the first breath of the MBNW, these indexes are poorly sensitive to the TO distribution or FS between the subunits. However, as the washout proceeds, the n dependence of both Sn and VDB becomes markedly distinct for simulations with different TO and FS. VDF increases only slightly with n during the MBNW for a large range of TO and FS combinations, and AME is independent of FS. Comparison of published experimental observations with model simulations gave a consistent picture of ventilation maldistribution in the human lung. MBNW simulations in conditions of weightlessness, which will be performed shortly in Spacelab, suggest that it will be possible to evaluate quantitatively the intraregional elastic inhomogeneities in the human lung.