A comparison of the dose-response behavior of canine airways and parenchyma

We compared the histamine responsiveness of canine airways and parenchymal tissues in six anesthetized paralyzed open-chest mongrel dogs, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue viscance (Vti). Pressure was measured during tidal breathing (frequency was 0.3 Hz) at the trachea and in three alveolar regions by use of alveolar capsules. Measurements were taken before and after the delivery of increasing concentrations of aerosolized histamine (0.1-30 mg/ml). We found that Vti accounted for 78 +/- 8% of RL under base-line conditions; this proportion remained relatively constant throughout the histamine concentration-response curve. There was a significant correlation between percent change in Vti and percent change in Raw at all levels of histamine-induced constriction (P less than 0.001). Moreover, the sensitivity of the tissues and airways (defined as the concentration of histamine required to double resistance) was remarkably similar. We conclude that, at this frequency of ventilation, Vti accounts for the major portion of RL both under base-line conditions and after histamine-induced constriction. Although increases in RL cannot be attributed solely to events occurring in the airways, the close correlation between changes in Raw and Vti and the similar sensitivities of the two support the use of indexes reflecting changes in airway caliber as an indicator of overall lung histamine responsiveness.     

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.     

Histamine-induced constriction of canine peripheral lung: an airway or tissue response?

We compared the histamine responsiveness of peripheral airways (less than 6.0 mm diam) and parenchymal tissues in eight anesthetized paralyzed open-chest mongrel dogs. We measured pressure in a peripheral bronchus by using an antegrade wedged catheter and pressure in the alveolar region subtended by the wedged bronchus by using an alveolar capsule. Sinusoidal volume oscillations at a frequency of 0.5 Hz were delivered by a linear motor pump into the segment through the wedged catheter. We calculated the resistance of the segment (Rseg) and partitioned Rseg into tissue viscance (i.e., proportional to the resistive pressure drop between the alveolus and the pleura) and peripheral airway resistance. Measurements were taken under baseline conditions and after delivery of increasing concentrations of aerosolized histamine (0.1 micrograms/ml to 100.0 mg/ml) into the segment. We found that the histamine responsiveness of the peripheral airways and lung tissues varied markedly within a given dog. In four of eight dogs the airways were more responsive to histamine, in three of eight the tissues were more responsive, and in one of eight the response was equivalent at the two sites. We conclude that in a given animal, there is marked heterogeneity in the histamine responsiveness of the peripheral airways and parenchymal tissues and that either may dominate responsiveness in the peripheral lung.     

Measurement of interrupter resistance in rabbits exposed to methacholine aerosols.

We studied the effect of increasing airway resistance on equilibration of airway and alveolar pressure during passive expiratory airflow interruption. In 10 anesthetized and paralyzed rabbits, airway and alveolar pressures were compared before and after airway resistance was increased with methacholine. In all studies, airway pressure rose to equilibrate with alveolar pressure immediately after the interruption (delta Pinit) regardless of increases in airway resistance. The pressures then remained equal during the interruption while gradually increasing to plateau (delta Pdiff). Before methacholine exposure, delta Pdiff was small (0.6 +/- 0.3 cmH2O). Steady-state resistance calculated from the sum of delta Pinit and delta Pdiff was similar to airway resistance calculated from delta Pinit alone. After methacholine, increased airway resistance was accompanied by increased delta Pdiff (2.0 +/- 0.5 cmH2O), causing disproportionate increase in steady-state resistance. delta Pdiff increases were equal in the airway and alveoli, implying resistive changes distal to the sampled alveoli. Thus increasing airway resistance did not delay pressure equilibration across airways. However, increases in airway resistance were accompanied by tissue resistive changes that were greater than the increases in airway resistance.     

Effects of aerosol histamine and carbachol on central and peripheral airflow resistance in sheep

Sixteen anesthetized artificially ventilated open-chest sheep were prepared with retrograde catheters to allow for measurement of dynamic compliance of the lungs (Cdyn), total airflow resistance of the lungs (RL), and central (Rc) and peripheral (Rp) airflow resistance. Twelve sheep received aerosol histamine and 12 sheep received aerosol carbachol. Eight sheep received and responded to both aerosol histamine and aerosol carbachol. Three sheep received both aerosol histamine and aerosol carbachol but failed to respond to both agents. Under base-line conditions, for the 16 sheep, 69% of total RL was located in the peripheral component, Rp, and 31% in the central component, Rc. Aerosol histamine caused only peripheral small airway changes while aerosol carbachol predominantly effected the central large airways. When aerosol histamine responsiveness, defined using Cdyn or Rp, was compared to aerosol carbachol responsiveness using Rc, a correlation was demonstrable (r = 0.84, n = 8, P less than 0.05). It is possible in sheep to cause relatively pure peripheral small airway and relatively pure central large airway changes by using different bronchoconstrictor agents. Aerosol histamine and aerosol carbachol responsiveness correlated with each other in these artificially ventilated anesthetized sheep.     

Partitioning of pulmonary resistance during constriction in the dog: effects of volume history

We assessed the relative changes in airways and lung tissue with bronchoconstriction, and the changes in each during and following a deep inhalation (DI). We partitioned pulmonary resistance (RL) into airway (Raw) and tissue (Vtis) components using alveolar capsules in 10 anesthetized, paralyzed, and open-chested dogs ventilated sinusoidally with 350-ml breaths at 1 Hz. We made measurements before and during bronchoconstriction induced by vagal stimulation or inhalation of histamine or prostaglandin F2 alpha (PGF2 alpha), each of which decreased dynamic compliance by approximately 40%. With histamine and PGF2 alpha the rise in RL was predominantly due to Vtis. With vagal stimulation there was a relatively greater increase in Raw than Vtis. At higher lung volumes, Vtis increases offset falls in Raw, producing higher RL at these volumes before and during constriction with PGF2 alpha and histamine. During constriction with vagal stimulation, the fall in Raw with inflation overrode the rise in Vtis, resulting in a lower RL at the higher compared with the lower lung volume. The changes seen after a DI in the control and constricted states were due to alterations in tissue properties, both viscous and elastic. However, the relative hysteresis of the airways and parenchyma were equal, since Raw, our index of airway size, was unchanged after a DI.     

Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction

Positive end-expiratory pressure (PEEP) has generally been withheld from the treatment of patients with chronic airflow obstruction (CAO), in view of the risk of hyperinflation and lack of documented benefit. We studied 10 mechanically ventilated patients with exacerbated CAO and air trapping to determine the impact of PEEP on lung mechanics, alveolar pressure, and the work of breathing. PEEP levels of 5 and 10 cmH2O were applied to patients whose end-expiratory alveolar pressures were documented to be positive when breathing against ambient pressure (the auto-PEEP effect). All patients were studied under two conditions: every breath machine assisted (AMV) and every breath machine controlled (paralyzed, CMV). PEEP improved expiratory resistance without substantially increasing peak static pressure. Inspiratory resistance remained unchanged. The difference between the end-expiratory values of alveolar and central airway pressure narrowed as PEEP increased. Adding PEEP improved the effective triggering sensitivity of the ventilator, diminished ventilatory drive, and reduced the mechanical work of breathing during the machine-assisted ventilatory cycle. Our results indicate that low levels of PEEP may improve lung mechanics and reduce the effort required of mechanically ventilated patients with severe airflow obstruction, without substantially increasing the hazards of hyperinflation.     

Interpretation of interrupter resistance after histamine-induced constriction in the dog

The interrupter method for measuring respiratory system resistance involves interrupting flow at the airway opening and measuring the resultant changes in pressure. We have recently shown (J. Appl. Physiol. 65: 408-414, 1988) that in open-chest mongrel dogs, under control conditions, the initial rapid pressure change (delta Pinit) reflects conducting airway resistance and the subsequent gradual pressure change (delta Pdif) reflects stress recovery of the tissues. We questioned whether the same interpretation would apply after induced constriction. Accordingly, we performed interruption experiments on anesthetized, paralyzed, tracheostomized, open-chest mongrel dogs during passive expiration, measuring pressure at the trachea and in three different alveolar regions with alveolar capsules. We recorded measurements before and after the administration of increasing concentrations of histamine aerosol (0.1-30.0 mg/ml). We found a significant increase in the heterogeneity of alveolar pressures during the relaxed expiration with increasing concentrations of histamine. Despite the introduction of significant mechanical heterogeneities, delta Pinit still reflected the pressure drop as the result of the resistance of the conducting airways. delta Pdif, however, reflected a combination of the stress recovery of the tissues and pendelluft.     

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.     

Biomechanical Aspects of Compliant Airways due to Mechanical Ventilation

Without proper knowledge of mechanical ventilation effects, physicians can aggravate an existing lung injury. A better understanding of the interaction between airflow and airway tissue during mechanical ventilation will be helpful to physicians so that they can provide appropriate ventilator parameters for intubated patients. In this study, a computational model incorporating the interactions between airflow and airway walls was developed to investigate the effects of airway tissue flexibility on airway pressure and stress. Two flow rates, 30 and 60 l/min, from mechanical ventilation were considered. The transient waveform was active inhalation with a constant flow rate and passive exhalation. Results showed that airway tissue flexibility decreased airway pressure at bifurcation sites by approximately 25.06% and 16.91% for 30 and 60 l/min, respectively, and increased wall shear stress (WSS) by approximately 74.00% and 174.91% for 30 and 60 l/min, respectively. The results from the present study suggested that it is very important to consider the interaction between airflow and airway walls when computational models are developed. Results of this study help to better quantify how the airflow rate used in mechanical ventilation, in conjunction with airway tissue flexibility, affects airway pressure and stresses.     

Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.     

Nonhomogeneity of lung response to inhaled histamine assessed with alveolar capsules

To assess the homogeneity of airway responses to inhaled histamine we examined regional alveolar pressure excursions (PA) arising from small-amplitude oscillations applied at the airway opening (Pao). In five anesthetized and vagotomized dogs the sternum was split and the anterior right lung field exposed. PA was sampled using four capsules affixed to the right apical and middle lobes while lung impedance (ZL) and airway impedances (Zaw) were measured during conventional tidal breathing and during forced oscillations (2-60 HZ at 10 cmH2O distending pressure). During tidal breathing after exposure to aerosol histamine regional PA's could be separated into three groups by plotting Lissajous figures of PA vs. Pao: PA in phase with Pao (no looping), PA lagging Pao (moderate looping), and PA decreasing while Pao was increasing and vice versa (paradoxical looping), suggesting unresponsive, responsive, and closed pathways, respectively, between the airway opening and specific alveolar zones. During high-frequency oscillation the corresponding PA spectra were markedly different from control spectra and revealed resonant amplification, overdamped resonance, and marked attenuation, respectively. With induced bronchospasm resonant amplification of PA was damped on average. However, the more obstructed and closed pathways were protected from resonant amplification, and the more open (nonlooping) pathways were subjected to resonant amplification greater than in the control state. In spite of this markedly nonhomogeneous behavior, frequency dependence of ZL was consistent with the model by Mead (J. Appl. Physiol. 26: 670-673, 1969), which ignores nonhomogeneity of peripheral compartments. These data demonstrate that the response of airways to inhaled histamine is nonhomogeneous but that frequency dependence of ZL above 2 Hz is not sufficient to characterize this nonhomogeneity.     

Effects of respiratory drive on upper airways in sleep apnea patients and normal subjects

We compared the changes in nasal and pharyngeal resistance induced by modifications in the central respiratory drive in 8 patients with sleep apnea syndrome (SAS) with the results of 10 normal men. Upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other above the uvula. Nasal and pharyngeal resistances were calculated at isoflow. During CO2 rebreathing and during the 2 min after maximal voluntary hyperventilation, we continuously recorded upper airway pressures, airflow, end-tidal CO2, and the mean inspiratory flow (VT/TI); inspiratory pressure generated at 0.1 s after the onset of inspiration (P0.1) was measured every 15-20 s. In both groups upper airway resistance decreased as P0.1 increased during CO2 rebreathing. When P0.1 increased by 500%, pharyngeal resistance decreased to 17.8 +/- 3.1% of base-line values in SAS patients and to 34.9 +/- 3.4% in normal subjects (mean +/- SE). During the posthyperventilation period the VT/TI fell below the base-line level in seven SAS patients and in seven normal subjects. The decrease in VT/TI was accompanied by an increase in upper airway resistance. When the VT/TI decreased by 30% of its base-line level, pharyngeal resistance increased to 319.1 +/- 50.9% in SAS and 138.5 +/- 4.7% in normal subjects (P less than 0.05). We conclude that 1) in SAS patients, as in normal subjects, the activation of upper airway dilators is reflected by indexes that quantify the central inspiratory drive and 2) the pharyngeal patency is more sensitive to the decrease of the central respiratory drive in SAS patients than in normal subjects.     

Role of thromboxane A2 in airway microvascular leakage induced by inhaled platelet-activating factor.

We studied the effects of OKY-046 (1, 10, and 30 mg/kg iv), a selective thromboxane synthase inhibitor, and of ICI 192605 (0.5 mg/kg), a selective thromboxane A2 receptor antagonist, on airflow obstruction and airway microvascular leakage induced by inhaled platelet-activating factor (PAF). Extravasated Evans blue dye content was measured as a reflection of airway microvascular leakage. In control animals, PAF caused a significantly higher increase in extravasation of dye and significantly less increase in lung resistance (RL) than histamine. OKY-046 significantly inhibited both changes in RL and airway microvascular leakage after PAF in a dose-dependent manner, whereas it inhibited histamine-induced airway microvascular leakage only at main bronchi, without any significant effect on RL. ICI 192605 significantly inhibited both RL and airway microvascular leakage induced by PAF, but not after histamine. After both PAF and histamine, changes in RL correlated significantly with the degree of microvascular leakage. Airway microvascular leakage and airflow obstruction after PAF, but not after histamine, may be dependent on thromboxane A2 generation.     

Partitioning of pulmonary responses to inhaled methacholine in puppies.

Twelve open-chest mongrel puppies, 8-10 wk old, were studied to localize the site of action of inhaled methacholine within the lungs. Six puppies were challenged with methacholine aerosols and six were challenged with an equal number of nebulizations of normal saline (control group). Pulmonary mechanics were measured during mechanical ventilation and after midexpiratory flow interruptions. Alveolar pressure was measured to allow the partitioning of pulmonary mechanics into airway and tissue components. Good matching between airway opening and alveolar pressures was seen throughout the study. After methacholine challenge, lung resistance increased fivefold. Increases in airway resistance and in the parameters reflecting tissue viscoelastic properties contributed to this increase in lung resistance. Dynamic lung elastance also increased threefold. The response of the methacholine group was statistically different from that of the control group. These data indicate that both the airways and pulmonary parenchyma contribute to the response to inhaled methacholine in 8- to 10-wk-old puppies.     

Partitioning of pulmonary resistance in dogs: effect of tidal volume and frequency

To determine the sensitivity of pulmonary resistance (RL) to changes in breathing frequency and tidal volume, we measured RL in intact anesthetized dogs over a range of breathing frequencies and tidal volumes centering around those encountered during quiet breathing. To investigate mechanisms responsible for changes in RL, the relative contribution of airway resistance (Raw) and tissue resistance (Rti) to RL at similar breathing frequencies and tidal volumes was studied in six excised, exsanguinated canine left lungs. Lung volume was sinusoidally varied, with tidal volumes of 10, 20, and 40% of vital capacity. Pressures were measured at three alveolar sites (PA) with alveolar capsules and at the airway opening (Pao). Measurements were made during oscillation at five frequencies between 5 and 45 min-1 at each tidal volume. Resistances were calculated by assuming a linear equation of motion and submitting lung volume, flow, Pao, and PA to a multiple linear regression. RL decreased with increasing frequency and decreased with increasing tidal volume in both isolated and intact lungs. In isolated lungs, Rti decreased with increasing frequency but was independent of tidal volume. Raw was independent of frequency but decreased with tidal volume. The contribution of Rti to RL ranged from 93 +/- 4% (SD) with low frequency and large tidal volume to 41 +/- 24% at high frequency and small tidal volume. We conclude that the RL is highly dependent on breathing frequency and less dependent on tidal volume during conditions similar to quiet breathing and that these findings are explained by changes in the relative contributions of Raw and Rti to RL.     

Immunologic and nonimmunologic responsiveness in ragweed-sensitized dogs

The relationship between airway responsiveness to inhaled antigen and histamine, immunologic release of lung histamine, immunologic responsiveness of skin, and specific immunoglobulin E (IgE) antibodies were examined in 11 inbred allergic dogs immunized with extracts of ragweed and grass and 5 nonimmunized control dogs from the same colony. Airway responsiveness to antigen and histamine was characterized by the doses that increased the airflow resistance of the total respiratory system to twice the control values (ED200). Highly significant correlations were found between airway responsiveness and cutaneous responsiveness to antigen and other immunologic characteristics (e.g., IgE and histamine released from lung by inhaled antigen) in all dogs. In ragweed-sensitized dogs, there was an inverse correlation between immunologic responsiveness (reflected by the cutaneous response to antigen and histamine released from lung by inhaled antigen) and nonimmunologic responsiveness of airways (histamine ED200: r = 0.73, P less than 0.05 and r = 0.75, P less than 0.01, respectively). Antigen ED200 was also correlated with histamine release from lung after antigen inhalation (r = 0.74; P less than 0.01). We conclude that airway reactions to inhaled antigen in allergic dogs are dependent not only on immunologic factors but also on the degree of nonimmunologic airway responsiveness to histamine and that these factors are correlated inversely.     

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.     

Resistance of intrathoracic airways of healthy subjects during periodic flow.

The resistance and reactance of lower airways were measured as functions of the frequency and amplitude of periodic flow in three healthy subjects by relating flow, produced with a piston pump, to the difference between lateral tracheal and alveolar pressure, estimated plethysmorgraphically. Resistance consistently increased with frequency; reactance was small never exceeding resistance. This result cannot be explained by distortion of velocity profiles by inertia because, in long pipes, resistance increases only when inertial forces are large and reactance exceeds resistance. Theoretical analyses of airway resistance suggested that the results reflected inhomogeneity. In lung models which considered airway wall distensibility and inertial reactance of airways, resistance increased with frequency and inertial reactance was small. These results imply that in health, as in lung disease, resistance is determined by the distribution of resistance and reactance within the lung and is not simply the total resistance of the individual airways. As flow amplitude increased at constant frequency, flow-pressure relationships became distorted and resistance increased, due probably to motion of airway walls and further distortion of velocity profiles     

Lung impedance in healthy humans measured by forced oscillations from 0.01 to 0.1 Hz

Lung impedance was measured from 0.01 to 0.1 Hz in six healthy adults by superimposing small-amplitude forced oscillations on spontaneous breathing. Measurements were made with an almost constant-volume input (160-180 ml) or with an almost constant-flow input (20-30 ml.s-1). No significant difference was found between the two conditions. Lung resistance (RL) sharply decreased from 0.97 kPa.l-1.s at 0.01 Hz to 0.27 kPa.l-1.s at 0.03 Hz and then mildly to 0.23 kPa.l-1.s at 0.1 Hz. Lung effective compliance (CL) decreased slightly and regularly from 0.01 Hz (2.38 l.kPa-1) to 0.1 Hz (1.93 l.kPa-1). The data were analyzed using a linear viscoelastic model adapted from Hildebrandt (J. Appl. Physiol. 28:365-372, 1970) and complemented by a Newtonian resistance (R): RL = R + B/(9.2f); CL = 1/(A + 0.25B + B.log2 pi f), where f is the frequency and B/A is an index of lung tissue viscoelasticity. A good fit was generally obtained, with an average difference of 10% between the observed and predicted values. The ratio B/A was not affected by the breathing and was 10.6 and 13.6% in the constant-volume and constant-flow conditions, respectively, which agrees with Hildebrandt's observations in isolated cat lungs. R was systematically larger than the plethysmographic airway resistance, suggesting that lung tissue resistance might also include a Newtonian component.