Respiratory tissue properties derived from flow transfer function in healthy humans

Tomalak, W., R. Peslin, and C. Duvivier. Respiratorytissue properties derived from flow transfer function in healthy humans. J. Appl. Physiol. 82(4):1098-1106, 1997.Assuming homogeneity of alveolar pressure, therelationship between airway flow and flow at the chest during forcedoscillation at the airway opening [flow transfer function(FTF)] is related to lung and chest wall tissue impedance (Zti):FTF = 1 + Zti/Zg, where Zg is alveolar gas impedance, which isinversely proportional to thoracic gas volume. By using a flow-typebody plethysmograph to obtain flow rate at body surface, FTF has beenmeasured at oscillation frequencies (f_os) of 10, 20, 30 and 40 Hz in eight healthy subjects during both quiet and deepbreathing. The data were corrected for the flow shunted through upperairway walls and analyzed in terms of tissue resistance (Rti) andeffective elastance (Eti,eff) by using plethysmographically measuredthoracic gas volume values. In most subjects, Rti was seen to decreasewith increasingf_os and Eti,effto vary curvilinearly withf_os²,which is suggestive of mechanical inhomogeneity. Rti presented a weakvolume dependence during breathing, variable in sign according tof_os and amongsubjects. In contrast, Eti,eff usually exhibited a U-shaped patternwith a minimum located a little above or below functional residualcapacity and a steep increase with decreasing or increasing volume(30-80 hPa/l²) on eitherside. These variations are in excess of those expected from the sigmoidshape of the static pressure-volume curve and may reflect the effect ofrespiratory muscle activity. We conclude that FTF measurement is aninteresting tool to study Rti and Eti,eff and that these parametershave probably different physiological determinants.

     

Time course of respiratory mechanics during histamine challenge in the dog.

We studied the dynamics of respiratory mechanical parameters in anesthetized tracheostomized paralyzed dogs challenged with a bolus of histamine injected either venously (venous group) or arterially (arterial group). The venous group was further divided into two groups: the first was bilaterally vagotomized and received hexamethonium bromide (denervated group), and the second also received atropine sulfate (atropine group). In the venous group, tissue resistance (Rti) and tissue elastance (Eti) increased biphasically, whereas airway resistance was monophasic and synchronized with the second rise of the tissue parameters. In the arterial group, Rti, Eti, and airway resistance increased synchronously. The denervated and atropine groups showed dynamics similar to those of the venous group. We postulate that the first phase observed in Rti and Eti in the venous group is due to constriction of the smooth muscles of the peripheral airways and blood vessels distorting the parenchyma. The second and larger phase is then due to histamine reaching the bronchial circulation and constricting the central airways, again distorting the parenchyma. The results from the arterial group support this hypothesis, whereas those from the denervated group ascertain that none of the phases observed in the venous group was due to nervous reflexes.     

Viscoelastic behavior of a lung alveolar duct model

A study is conducted into the oscillatory behavior of a finite element model of an alveolar duct. Its load-bearing components consist of a network of elastin and collagen fibers and surface tension acting over the air-liquid interfaces. The tissue is simulated using a visco-elastic model involving nonlinear quasi-static stress-strain behavior combined with a reduced relaxation function. The surface tension force is simulated with a time- and area-dependent model of surfactant behavior. The model was used to simulate lung parenchyma under three surface tension cases: air-filled, liquid-filled, and lavaged with 3-dimenthyl siloxane, which has a constant surface tension of 16 dyn/cm. The dynamic elastance (Edyn) and tissue resistance (Rti) were computed for sinusoidal tidal volume oscillations over a range of frequencies from 0.16-2.0 Hz. A comparison of the variation of Edyn and Rti with frequency between the model and published experimental data showed good qualitative agreement. Little difference was found in the model between Rti for the air-filled and lavaged models; in contrast, published data revealed a significantly higher value of Rti in the lavaged lung. The absence of a significant increase in Rti for the lavaged model can be attributed to only minor changes in the individual fiber bundle resistances with changes in their configuration. The surface tension was found to make an important contribution to both Edyn and Rti in the air-filled duct model. It was also found to amplify any existing tissue dissipative properties, despite exhibiting none itself over the small tidal volume cycles examined.     

Size distribution of recruited alveolar volumes in airway reopening.

In 11 isolated dog lung lobes, we studied the size distribution of recruited alveolar volumes that become available for gas exchange during inflation from the collapsed state. Three catheters were wedged into 2-mm-diameter airways at total lung capacity. Small-amplitude pseudorandom pressure oscillations between 1 and 47 Hz were led into the catheters, and the input impedances of the regions subtended by the catheters were continuously recorded using a wave tube technique during inflation from -5 cm H(2)O transpulmonary pressure to total lung capacity. The impedance data were fit with a model to obtain regional tissue elastance (Eti) as a function of inflation. First, Eti was high and decreased in discrete jumps as more groups of alveoli were recruited. By assuming that the number of opened alveoli is inversely proportional to Eti, we calculated from the jumps in Eti the distribution of the discrete increments in the number of opened alveoli. This distribution was in good agreement with model simulations in which airways open in cascade or avalanches. Implications for mechanical ventilation may be found in these results.     

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.     

Tissue and airway impedance of excised normal, senile, and emphysematous lungs.

We partitioned pulmonary resistance (RL) in excised normal, senile, and emphysematous human lungs at various distending pressures; peripheral resistance (Rp) was measured by means of retrograde catheters and lung tissue resistance (Rti) by means of pleural capsules. By subtracting Rp from RL and Rti from Rp, we obtained, respectively, central (Rcaw) and peripheral (Rpaw) airway resistance. We determined also lung volumes, the elastic recoil pressure-volume curve, and the forced expiratory volume in 1 s-to-vital capacity ratio (FEV1/VC). The functional data were related to morphometry: mean linear intercept (Lm), diameter (d), and density (n/cm2) of membranous bronchioles. In the three groups of lungs, Rti demonstrates a marked negative frequency dependence and increases with transplumonary pressure. In emphysematous lungs, the increase of RL is mainly due to an increase of Rpaw; in addition, Rcaw and Rti are higher than normal. In the group of senile lungs, airway resistances are within normal range, but Rti is slightly increased. FEV1/VC is related to Rpaw and elastic recoil pressure; Rpaw is related to d and n/cm2, and Rti is related to dynamic elastance and to Lm.     

Lung tissue resistance during contractile stimulation: structural damping decomposition.

Research in the mechanics of soft tissue, and lung tissue in particular, has emphasized that dissipative processes depend predominantly on the viscous stress. A corollary is that dissipative losses may be expressed as a tissue viscous resistance, (Rti). An alternative approach is offered by the structural damping hypothesis, which holds that dissipative processes within soft tissue depend directly more on the elastic stress than on the viscous stress. This implies that dissipative and elastic processes within lung tissues are coupled at a fundamental level. We induced alterations of Rti by exposing canines to aerosols of the constrictors prostaglandin F2 alpha, histamine, and methacholine and by changing volume history. Using the structural damping paradigm, we could separate those alterations in Rti into the product of two distinct contributions: change in the coefficient of coupling of dissipation to elastance (eta) and change in the elastance itself (Edyn). Response of Edyn accounted for most of the response of resistance associated with contractile stimulation; it accounted for almost all the response associated with differences in volume history. The eta changed appreciably with constriction but accounted for little of the response of Rti with volume history. According to the structural damping hypothesis, induced changes in eta with constriction must reflect changes in the kinetics of the stress-bearing process, i.e., differences in cross-bridge kinetics within the target contractile cell and/or differences in the influence of the target cell on other stress-bearing systems. We conclude that, regardless of underlying processes, the structural damping analysis demonstrates a fundamental phenomenological simplification: when Edyn responds, Rti is obligated to respond to a similar degree.     

Partitioning airway and lung tissue resistances in humans: effects of bronchoconstriction

Kaczka, David W., Edward P. Ingenito, Bela Suki, and KennethR. Lutchen. Partitioning airway and lung tissue resistances inhumans: effects of bronchoconstriction. J. Appl.Physiol. 82(5): 1531-1541, 1997.The contributionof airway resistance(Raw) and tissue resistance(Rti) to totallung resistance(RL)during breathing in humans is poorly understood. We have recentlydeveloped a method for separating Rawand Rti from measurements ofRLand lung elastance (EL)alone. In nine healthy, awake subjects, we applied a broad-band optimalventilator waveform (OVW) with energy between 0.156 and 8.1 Hz thatsimultaneously provides tidal ventilation. In four of the subjects,data were acquired before and during a methacholine (MCh)-bronchoconstricted challenge. TheRLandELdata were first analyzed by using a model with a homogeneous airwaycompartment leading to a viscoelastic tissue compartment consisting oftissue damping and elastance parameters. Our OVW-based estimates ofRaw correlated well with estimatesobtained by using standard plethysmography and were responsive toMCh-induced bronchoconstriction. Our data suggest thatRti comprises ~40% of totalRLat typical breathing frequencies, which corresponds to ~60% ofintrathoracic RL. During mildMCh-induced bronchoconstriction, Rawaccounts for most of the increase inRL. At high doses of MCh, therewas a substantial increase in RLat all frequencies and inEL athigher frequencies. Our analysis showed that bothRaw andRti increase, but most of the increaseis due to Raw. The data also suggestthat widespread peripheral constriction causes airway wall shunting toproduce additional frequency dependence inEL.

     

Determination of airway and tissue resistances after antigen and methacholine in nonhuman primates

Madwed, Jeffrey B., and Andrew C. Jackson.Determination of airway and tissue resistances after antigen andmethacholine in nonhuman primates. J. Appl.Physiol. 83(5): 1690-1696, 1997.Antigen challenge of Ascaris suum-sensitiveanimals has been used as a model of asthma in humans. However, noreports have separated total respiratory resistance into airway (Raw)and tissue (Rti) components. We compared input impedance (Zin) andtransfer impedance (Ztr) to determine Raw and Rti in anesthetizedcynomolgus monkeys under control and bronchoconstricted conditions. Zindata between 1 and 64 Hz are frequency dependent during baselineconditions, and this frequency dependence shifts in response toA. suum or methacholine. Thus itcannot be modeled with the DuBois model, and estimates of Raw and Rticannot be determined. With Ztr, baseline data were much less variablethan Zin in all monkeys. After bronchial challenge withA. suum or methacholine, the absoluteamplitude of the resistive component of Ztr increased and its zerocrossing shifted to higher frequencies. These data can estimate Raw and Rti with the six-element DuBois model. Therefore, in monkeys, Ztr hasadvantages over other measures of lung function, since it provides amethodology to separate estimates of Raw and Rti. In conclusion, Ztrshows spectral features similar to those reported in healthy andasthmatic humans.

     

Flow and volume dependence of respiratory mechanical properties studied by forced oscillation

The influence of inspiratory and expiratory flow magnitude, lung volume, and lung volume history on respiratory system properties was studied by measuring transfer impedances (4-30 Hz) in seven normal subjects during various constant flow maneuvers. The measured impedances were analyzed with a six-coefficient model including airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility. Increasing respiratory flow from 0.1 to 0.4 1/s was found to increase inspiratory and expiratory Raw by 63% and 32%, respectively, and to decrease Iaw, but did not change tissue properties. Raw, Iti, and Cti were larger and Rti was lower during expiration than during inspiration. Decreasing lung volume from 70 to 30% of vital capacity increased Raw by 80%. Cti was larger at functional residual capacity than at the volume extremes. Preceding the measurement by a full expiration rather than by a full inspiration increased Iaw by 15%. The data suggest that the determinants of Raw and Iaw are not identical, that airway hysteresis is larger than lung hysteresis, and that respiratory muscle activity influences tissue properties.     

Halothane decreases both tissue and airway resistances in excised canine lungs

Studies of the anesthetic effects on the airway often use pulmonary resistance (RL) as an index of airway caliber. To determine the effects of the volatile anesthetic, halothane, on tissue and airway components of RL, we measured both components in excised canine lungs before and during halothane administration. Tissue resistance (Rti), airway resistance (Raw), and dynamic lung compliance (CL, dyn) were determined at constant tidal volume and at ventilatory frequencies ranging from 5 to 45 min-1 by an alveolar capsule technique. Halothane decreased RL at each breathing frequency by causing significant decreases in both Raw and Rti but did not change the relative contribution of Rti to RL at any frequency. Halothane increased CL,dyn at each breathing frequency, although there was little change in the static pressure-volume relationship. The administration of isoproterenol both airway and tissue components of RL; it may act by relaxing the contractile elements in the lung. Both components must be considered when the effects of volatile anesthetics on RL are interpreted.     

Endogenous nitric oxide modulates responses of tissue and airway resistance to vagal stimulation in piglets.

The role of endogenous nitric oxide (NO) in modulating the excitatory response of distal airways to vagal stimulation is unknown. In decerebrate, ventilated, open-chest piglets aged 3-10 days, lung resistance (RL) was partitioned into tissue resistance (Rti) and airway resistance (Raw) by using alveolar capsules. Changes in RL, Rti, and Raw were evaluated during vagal stimulation at increasing frequency before and after NO synthase blockade with N(omega)-nitro-L-arginine methyl ester (L-NAME). Vagal stimulation increased RL by elevating both Rti and Raw. NO synthase blockade significantly increased baseline Rti, but not Raw, and significantly augmented the effects of vagal stimulation on both Rti and Raw. Vagal stimulation also resulted in a significant increase in cGMP levels in lung tissue before, but not after, L-NAME infusion. In seven additional piglets after RL was elevated by histamine infusion in the presence of cholinergic blockade with atropine, vagal stimulation failed to elicit any change in RL, Rti, or Raw. Therefore, endogenous NO not only plays a role in modulating baseline Rti, but it opposes the excitatory cholinergic effects on both the tissue and airway components of RL. We speculate that activation of the NO/cGMP pathway during cholinergic stimulation plays an important role in modulating peripheral as well as central contractile elements in the developing lung.     

Airway resistance and tissue elastance from input or transfer impedance in bronchoconstricted monkeys.

Ascaris suum (AS) challenge in nonhuman primates is used as an animal model of human asthma. The primary goal of this study was to determine whether the airways and respiratory tissues in monkeys that are bronchoconstricted by AS inhalation behave similarly to those in asthmatic humans. Airway resistance (Raw) and tissue elastance (Eti) were estimated from respiratory system input (Zin) or transfer (Ztr) impedance. Zin (0.4-20 Hz) and Ztr (2-128 Hz) were measured in anesthetized cynomolgus monkeys (n = 10) under baseline (BL) and post-AS challenge conditions. Our results indicate that AS challenge in monkeys produces 1) predominantly an increase in Raw and not tissue resistance, 2) airway wall shunting at higher AS doses, and 3) heterogeneous airway constriction resulting in a decrease of lung parenchyma effective compliance. We investigated whether the airway and tissue properties estimated from Zin and Ztr were similar and found that Raw estimated from Zin and Ztr were correlated [r(2) = 0.76], not significantly different at BL (13.6 +/- 1.4 and 13.1 +/- 0.9 cmH(2)O. l(-1). s(-1), respectively), but significantly different post-AS (20.5 +/- 4.5 cmH(2)O. l(-1). s(-1) and 18.5 +/- 5.2 cmH(2)O. l(-1). s(-1)). There was no correlation between Eti estimated from Zin and Ztr. The changes in lung mechanical properties in AS-bronchoconstricted monkeys are similar to those recently reported in human asthma, confirming that this is a reasonable model of human asthma.     

Mechanical and gas-distribution behavior of a collateral ventilation model

We extended the theoretical analysis of Otis et al. (J. Appl. Physiol. 8: 427-443, 1956) to study the effects of collateral ventilation on lung mechanics and gas distribution. Equations were developed to express the effective compliance, the effective resistance, and the distribution of airflow and tidal volume in a two-compartment model incorporating a collateral communication. The analysis of the model showed that, in general, collateral ventilation tends to attenuate the degree of frequency dependence of compliance and resistance, the magnitude of this effect being dependent on the mechanical properties of the model, including collateral resistance. The influence of collateral ventilation is important when the model simulates the mechanical characteristics of the emphysematous lung (marked time-constant inequality with regionally high airway resistance, and relatively low collateral resistance). Under these conditions, a large fraction of the tidal volume of the high airway resistance lung compartment is contributed by the collateral communication. The effects of collateral ventilation on the mechanical behavior of the model are negligible when collateral resistance largely exceeds airway resistance (simulating experimental findings in normal lungs). The present theoretical data suggest that the use of equations based on a model incorporating collateral ventilation is justified, at least in predicting the mechanical and gas-distribution behavior of the lung in emphysema.     

Changes in proteoglycans and lung tissue mechanics during excessive mechanical ventilation in rats

Excessive mechanical ventilation results in changes in lung tissue mechanics. We hypothesized that changes in tissue properties might be related to changes in the extracellular matrix component proteoglycans (PGs). The effect of different ventilation regimens on lung tissue mechanics and PGs was examined in an in vivo rat model. Animals were anesthetized, tracheostomized, and ventilated at a tidal volume of 8 (VT(8)), 20, or 30 (VT(30)) ml/kg, positive end-expiratory pressure of 0 (PEEP(0)) or 1.5 (PEEP(1.5)) cmH(2)O, and frequency of 1.5 Hz for 2 h. The constant-phase model was used to derive airway resistance, tissue elastance, and tissue damping. After physiological measurements, one lung was frozen for immunohistochemistry and the other was reserved for PG extraction and Western blotting. After 2 h of mechanical ventilation, tissue elastance and damping were significantly increased in rats ventilated at VT(30)PEEP(0) compared with control rats (ventilated at VT(8)PEEP(1.5)). Versican, basement membrane heparan sulfate PG, and biglycan were all increased in rat lungs ventilated at VT(30)PEEP(0) compared with control rats. At VT(30)PEEP(0), heparan sulfate PG and versican staining became prominent in the alveolar wall and airspace; biglycan was mostly localized in the airway wall. These data demonstrate that alterations in lung tissue mechanics with excessive mechanical ventilation are accompanied by changes in all classes of extracellular matrix PG.     

Functional Lung Imaging during HFV in Preterm Rabbits

Although high frequency ventilation (HFV) is an effective mode of ventilation, there is limited information available in regard to lung dynamics during HFV. To improve the knowledge of lung function during HFV we have developed a novel lung imaging and analysis technique. The technique can determine complex lung motion information in vivo with a temporal resolution capable of observing HFV dynamics. Using high-speed synchrotron based phase contrast X-ray imaging and cross-correlation analysis, this method is capable of recording data in more than 60 independent regions across a preterm rabbit lung in excess of 300 frames per second (fps). This technique is utilised to determine regional intra-breath lung mechanics of preterm rabbit pups during HFV. Whilst ventilated at fixed pressures, each animal was ventilated at frequencies of 1, 3, 5 and 10 Hz. A 50% decrease in delivered tidal volume was measured at 10 Hz compared to 1 Hz, yet at the higher frequency a 500% increase in minute activity was measured. Additionally, HFV induced greater homogeneity of lung expansion activity suggesting this ventilation strategy potentially minimizes tissue damage and improves gas mixing. The development of this technique permits greater insight and further research into lung mechanics and may have implications for the improvement of ventilation strategies used to support severe pulmonary trauma and disease.     

Lung tissue behavior in the mouse during constriction induced by methacholine and endothelin-1

Nagase, Takahide, Hirotoshi Matsui, Tomoko Aoki, YasuyoshiOuchi, and Yoshinosuke Fukuchi. Lung tissue behavior in the mouseduring constriction induced by methacholine and endothelin-1. J. Appl. Physiol. 81(6):2373-2378, 1996.Recently, mice have been extensively used toinvestigate the pathogenesis of pulmonary disease because appropriatemurine models, including transgenic mice, are being increasinglydeveloped. However, little information about the lung mechanics of miceis currently available. We questioned whether lung tissue behavior andthe coupling between dissipative and elastic processes, hysteresivity(), in mice would be different from those in the other species. Toaddress this question, we investigated whether tissue resistance (Rti)and  in mice would be affected by varying lung volume, constrictioninduced by methacholine (MCh) and endothelin-1 (ET-1), andhigh-lung-volume challenge during induced constriction. From measuredtracheal flow and tracheal and alveolar pressures in open-chest ICRmice during mechanical ventilation [tidal volume = 8 ml/kg,frequency (f) = 2.5 Hz], we calculated lung resistance(RL), Rti, airway resistance(Raw), lung elastance (EL),and  (=2fRti/EL). Underbaseline conditions, increasing levels of end-expiratory transpulmonarypressure decreased Raw and increased Rti. The administration ofaerosolized MCh and intravenous ET-1 increasedRL, Rti, Raw, andEL in a dose-dependent manner.Rti increased from 0.207 ± 0.010 to 0.570 ± 0.058 cmH₂O ^· ml^{1 ·} safter 10⁷ mol/kg ET-1(P < 0.01). After inducedconstriction, increasing end-expiratory transpulmonary pressuredecreased Raw. However,  was not affected by changing lung volume,constriction induced by MCh and ET-1, or high-lung-volume challengeduring induced constriction. These observations suggest that1)  is stable in mice regardlessof various conditions, 2) Rti is animportant fraction of RL andincreases after induced constriction, and3) mechanical interdependence mayaffect airway smooth muscle shortening in this species. In mammalianspecies, including mice, analysis of  may indicate that both Rti andEL essentially respond to asimilar degree.

     

Volume dependence of airway and tissue impedances in mice.

We measured respiratory input impedance (1-25 Hz) in mice and obtained parameters for airway and tissue mechanics by model fitting. Lung volume was varied by inflating to airway opening pressure (Pao) between 0 and 20 cm H2O. The expected pattern of changes in respiratory mechanics with increasing lung volume was seen: a progressive fall in airway resistance and increases in the coefficients of tissue damping and elastance. A surprising pattern was seen in hysteresivity (eta), with a plateau at low lung volumes (Pao < 10 cm H2O), a sharp fall occurring between 10 and 15 cm H2O, and eta approaching a second (lower) plateau at higher lung volumes. Studies designed to elucidate the mechanism(s) behind this behavior revealed that this was not due to chest wall properties, differences in volume history at low lung volume, time dependence of volume recruitment, or surface-acting forces. Our data are consistent with the notion that at low lung volumes the mechanics of the tissue matrix determine eta, whereas at high lung volumes the properties of individual fibers (collagen) become more important.     

Low-frequency pulmonary impedance in rabbits and its response to inhaled methacholine.

We assessed pulmonary mechanics in six open-chest rabbits (3 young and 3 adult) by the forced oscillation technique between 0.16 and 10.64 Hz. Under control conditions, pulmonary resistance (RL) decreased markedly between 0.16 and 4 Hz, after which it became reasonably constant. Measurements of alveolar pressure from two alveolar capsules in each rabbit showed that the large decrease of RL with increasing frequency below 4 Hz was due to lung tissue rheology and that tissue resistance was close to zero above 4 Hz. Estimates of resistance and elastance, also obtained by fitting tidal ventilation data at 1 Hz to the equation of the linear single-compartment model, gave values for RL motion that were slightly higher than those obtained by forced oscillations at the same frequency, presumably because of the flow dependence of airways resistance. After treatment with increasing doses of aerosolized methacholine, RL and pulmonary elastance between 0.16 and 1.34 Hz progressively increased, as did the point at which the pulmonary reactance crossed zero (the resonant frequency). The alveolar pressure measurements showed the lung to become increasingly inhomogeneously ventilated in all six animals, whereas in the three younger rabbits lobar atelectasis developed at high methacholine concentrations and the alveolar capsules ceased to communicate with the central airways. We conclude that the low-frequency pulmonary impedance of rabbits exhibits the same qualitative features observed in other species and that it is a sensitive indicator of the changes in pulmonary mechanics occurring during bronchoconstriction.     

Site of action of hypertonic saline in the canine lung.

The site of action of inhaled hypertonic saline was determined in 8- to 10-wk-old puppies by combining measurements of respiratory mechanics, made during mechanical ventilation and after midexpiratory flow interruptions, with direct measurements of alveolar pressure. Under both control conditions and after inhalation of 10% saline, we were able to partition lung mechanics into components representing the airways and tissue viscoelastic properties. Hypertonic saline challenge altered lung mechanics by increasing airway resistance and did not have any effect on elastic or viscoelastic properties of the lung.