Alveolar pressure nonhomogeneity during small-amplitude high-frequency oscillation

In six excised canine lungs, regional alveolar pressures (PA) were measured during small-amplitude high-frequency oscillations applied at the airway opening. Both the regional distribution of PA's and their relationship to pressure excursions at the airway opening (Pao) were assessed in terms of amplitude and phase. PA was sampled in several capsules glued to the pleural surface and communicating with alveolar gas via pleural punctures. Pao and PA were measured over the frequency (f) range 1-60 Hz, at transpulmonary pressures (PL) of 5, 10, and 25 cmH2O. The amplitude of PA excursions substantially exceeded Pao excursions at frequencies near the resonant frequency. At resonance the ratio [PA/Pao] was 1.9, 2.9, and 4.8 at PL's of 5, 10, and 25 cmH2O, respectively. Both spatial homogeneity and temporal synchrony of PA's between sampled lung regions decreased with f and increased with PL. Interregional variability of airway impedance [(Pao - PA)/Vao] and tissue impedance (PA/Vao) tended to be larger than differences due to changing PL but not as large as between-dog variability. These data define the baseline nonhomogeneity of the normal canine lung and also suggest that there may be some advantage in applying high-frequency ventilation at frequencies at least as high as lung resonant frequency.     

Inhomogeneity during deflation of excised canine lungs. II. Alveolar volumes

We have previously demonstrated appreciable inhomogeneity of alveolar pressures measured by a capsule technique in excised canine lobes deflated at submaximal flows (J. Appl. Physiol. 65: 1757-1765, 1988). We further analyzed the results of these experiments by estimating alveolar volumes (VA) and regional flows from regional transpulmonary pressures, assuming that regional pressure-volume relationships were homogeneous. Deflation at submaximal flows of lungs suspended in air caused significant flow-dependent inhomogeneity of VA that increased as lung volume decreased. Immersion of lungs in stable foams that simulated the gradient of pleural pressure modified the pattern of emptying, but not always to a gravity-dependent sequence. Limitation of regional expiratory flow was often asynchronous during both air suspension and foam immersion. There was no evidence of a common regional flow-volume curve. Submaximal deflation is a complex heterogeneous process, with the interregional pattern of emptying determined by the interaction of factors that are both intrinsic and extrinsic to the lungs.     

Inhomogeneity during deflation of excised canine lungs. I. Alveolar pressures

Factors both intrinsic and extrinsic to the lung may cause inhomogeneity of alveolar pressures during deflation. Wilson et al. (J. Appl. Physiol. 59: 1924-1928, 1985) predicted that any such inhomogeneity would be limited by interdependence of regional expiratory flows. To test this hypothesis and to explore how the pleural pressure gradient might affect inhomogeneity of alveolar pressures, we deflated at submaximal flows excised canine lobes that first were suspended in air and then were immersed in foams that simulated the vertical gradient of pleural pressure. Interregional inhomogeneity of regional transpulmonary pressures was measured with use of an alveolar capsule technique. Flow-dependent inhomogeneity of alveolar pressures was present, with differences in alveolar pressure quickly relaxing to a constant limiting value at each flow. Foam immersion increased inhomogeneity at a given flow. We conclude that factors intrinsic to the lung cause significant inhomogeneity of alveolar pressures at submaximal expiratory flows and that this inhomogeneity is enhanced by the extrinsic gradient of pleural pressure. These observations are consistent with the interdependence of flow proposed by Wilson et al.     

Alveolar pressure inhomogeneity and gas exchange during constant-flow ventilation in dogs

Analysis of momentum transfer between inflow jets and resident gas during constant-flow ventilation (CFV) predicts inhomogeneity of alveolar pressures (PA) and volume, which might account for specific ventilation-variance in the lung. Using alveolar needles to measure pressures (PA) during CFV in eight anesthetized dogs with wide thoracotomy, we observed random dispersion of PA among lobes of up to 12.5 cmH2O. Within each lobe, the PA dispersion was up to 10 cmH2O at CFV of 90 l/min; when flow decreased, PA at all sites decreased, as did the intralobar dispersion. These pressure differences were not observed during conventional mechanical ventilation (CMV). During CFV with room air, dogs were hypoxemic [arterial PO2 (Pao2) 54 +/- 15 Torr] and the venous admixture (Qva/QT) was 50 +/- 15%. When inspiratory O2 fraction was increased to 0.4, Pao2 increased to 172 +/- 35 Torr and Qva/QT dropped to 13.5 +/- 8.4%, confirming considerable ventilation-perfusion (VA/Q) variance not observed during CMV. We conclude that momentum transfer between the inflow stream and resident gas caused inhomogeneities of alveolar pressures, volumes, and ventilation responsible for VA/Q variance and hypoxemia during CFV. Conceivably, the abnormal ventilation distribution is minimized by collateral ventilation and forces of interdependence between regions of high and low alveolar pressures. Momentum transfer also predicted the mucosal damage observed on histological evaluation of the bronchial walls near the site of inflow jet impact.     

Alveolar liquid clearance in multiple nonperfused canine lung lobes

Grimme, John D., Susan M. Lane, and Michael B. Maron.Alveolar liquid clearance in multiple nonperfused canine lung lobes. J. Appl. Physiol. 82(1):348-353, 1997.We evaluated the ability of canine isolatednonperfused lung lobes to absorb fluid from their air spaces bysimultaneously measuring alveolar liquid clearance (ALC) in three lobesremoved from the same dog. Autologous plasma was instilled in the airspaces of each lobe, and the increase in plasma protein concentrationresulting from fluid reabsorption was used to calculate ALC. ALC after4 h was 16.5 ± 0.6% (SE) of the instilled fluid volume underbaseline conditions and was 30.2 ± 1.3% after terbutaline(10⁵ M) administration.These values were similar to those previously reported for intact dogs.Propranolol (10⁴ M) andouabain (10³ M) reduced ALCin terbutaline-stimulated lobes to 20.4 ± 0.8 and 3.9 ± 1.4%,respectively. There was no significant difference in ALC among thethree lobes under either baseline conditions or after terbutalineadministration. These data indicate that the sodium and water transportmechanisms of the canine alveolar epithelium remain viable during 4 hof nonperfusion and that there are no intrinsic differences in thetransport properties of individual lung lobes. The ability to studyseveral lobes simultaneously without the need for perfusion will allowfor the design of experiments in which multiple interventions can bestudied by using lung lobes from the same animal.

     

Extra-alveolar vessel fluid filtration coefficients in excised and in situ canine lobes

We continuously weighed fully distended excised or in situ canine lobes to estimate the fluid filtration coefficient (Kf) of the arterial and venous extra-alveolar vessels compared with that of the entire pulmonary circulation. Alveolar pressure was held constant at 25 cmH2O after full inflation. In the in situ lobes, the bronchial circulation was interrupted by embolization. Kf was estimated by two methods (Drake and Goldberg). Extra-alveolar vessels were isolated from alveolar vessels by embolizing enough 37- to 74-micron polystyrene beads into the lobar artery or vein to completely stop flow. In excised lobes, Kf's of the entire pulmonary circulation by the Drake and Goldberg methods were 0.122 +/- 0.041 (mean +/- SD) and 0.210 +/- 0.080 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. Embolization was not found to increase the Kf's. The mean Kf's of the arterial extra-alveolar vessels were 0.068 +/- 0.014 (Drake) and 0.069 +/- 0.014 (Goldberg) (24 and 33% of the Kf's for the total pulmonary circulation). The mean Kf's of the venous extra-alveolar vessels were similar [0.046 +/- 0.020 (Drake) and 0.065 +/- 0.036 (Goldberg) or 33 and 35% of the Kf's for the total circulation]. No significant difference was found between the extra-alveolar vessel Kf's of in situ vs. excised lobes. These results suggest that when alveolar pressure, lung volume, and pulmonary vascular pressures are high, approximately one-third of the total fluid filtration comes from each of the three compartments.     

Micropuncture measurement of alveolar liquid pressure in excised dog lung lobes

We have investigated the mechanism of alveolar liquid filling in pulmonary edema. We excised, degassed, and intrabronchially filled 14 dog lung lobes from nine dogs with 75, 150, 225, or 350 ml of 5% albumin solution, and then air inflated the lobes to a constant airway pressure of 25 cmH2O. By use of micropipettes, we punctured subpleural alveoli to measure alveolar liquid pressure by the servo-null technique. Alveolar liquid pressure was constant in all lobes despite differences in lobe liquid volume and averaged 10.6 +/- 1.3 cmH2O. Thus, in all lobes a constant pressure drop of 14.4 cmH2O existed from airway to alveolar liquid across the air-liquid interface. We attribute this finding, on the basis of the Laplace equation, to an air-liquid interface of constant radius in all the lobes. In fact, we calculated from the Laplace equation an air-liquid interface radius which equalled morphological estimates of alveolar radius. We conclude that in the steady state, alveoli that contained liquid have a constant radius of curvature of the air-liquid interface possibly because they are always completely liquid filled.     

Regional ventilation in excised lobes exposed to a transpulmonary pressure gradient

We performed the quasi-static single-breath oxygen test (SBO2) in 16 excised canine lower lung lobes while the lobes were first suspended in air and then later immersed in stable foams that provided a vertical transpulmonary pressure gradient. In lobes suspended in air, an approximately linear alveolar plateau (AP) was obtained. The AP during foam immersion was markedly curvilinear, with phase IV seen at end expiration. The observed AP during foam immersion could be predicted by a mathematical model that assumed a homogeneous transpulmonary pressure-regional volume relationship equal to the overall pressure-volume (PV) relationship measured with the lobe suspended in air. The accuracy of this model was further confirmed by measuring the washout of nitrogen injected into different lung regions through alveolar capsules. We also used the model to examine the relationship between the onset of dependent airway closure and two of its proposed indicators: the onset of phase IV and the inflection point of the overall PV relationship. In most lobes, the lung volume at the onset of phase IV was less than the modeled lung volume at dependent airway closure. The lung volume at the inflection point was always less than the modeled lung volume at dependent airway closure. We show that the overall PV relationship measured in lobes suspended in air provides an accurate estimate of regional PV relationships during foam immersion.     

Alveolar liquid pressure in excised edematous dog lung with increased static recoil

Alveolar liquid pressure (Pliq) was measured by micropipettes in conjunction with a servo-nulling pressure measuring system in isolated air-inflated edematous dog lungs. Pliq was measured in lungs either washed with a detergent (0.01% Triton X-100) or subjected to refrigeration for 2-3 days followed by ventilation for 3 h. At 55% of total lung capacity (TLC, the volume at a transpulmonary pressure (Ptp) of 25 cmH2O before treatment), in both the Triton-washed and the ventilated lung, Ptp increased from 5 to 11 cmH2O, whereas Pliq, decreased from -3 to -11 cmH2O relative to alveolar air pressure. Similar increases in Ptp and decreases in Pliq were obtained at higher lung volumes. Alveolar surface tension (T) was estimated from the Laplace equation for a spherical air-liquid interface, assuming that the radius of curvature varies as (volume)n, for -1/3 less than n less than 1/3. For uniform expansion of alveoli (n = 1/3), estimated T was 6 and 18 dyn/cm at 55 and 85% TLC, respectively, before treatment and increased to 23 and 40 dyn/cm following either Triton washing or ventilation. If pericapillary interstitial fluid pressure (Pi) equaled Pliq in edematous lungs, increases in T might reduce Pi and increase extravascular fluid accumulation in lungs made stiff by either Triton washing or cooling and ventilation using large tidal volumes.     

Ventilation heterogeneity in excised lobes: effect of tidal volume.

Although several factors are known to influence nonuniformity of ventilation, including lung mechanical properties (regional structure and compliance), external factors (chest wall, pleural pressure, heart), and ventilatory parameters (tidal and preinspiratory volume, flow rate), their relative contributions are poorly understood. We studied five excised, unperfused, canine right-middle lobes under varied levels of tidal volume (VT), thus eliminating many factors affecting heterogeneity. Multiple-breath washouts of N(2) were analyzed for anatomic dead space volume (VD(anat)), nonuniformity of N(2) washout, and nonuniformity between joined acinar regions vs. that occurring between larger joined regions. Approximately 80% of ventilation heterogeneity was found among joined acinar regions at resting levels of VT, but increasing VT reduced intra-acinar heterogeneity to about 25% of that found at resting levels. Increasing VT had essentially no effect on VD(anat) and heterogeneity among larger joined regions. The results indicate that the magnitude of VT is a major influence on the dominant intra-acinar component of ventilation heterogeneity and that VT effects on VD(anat) are likely due to perfusion and/or influences normally external to the lobar structure.