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Biomedical subjects

B Suki

Publications and source records attributed to B Suki.

At least 55 records · Page 3Linked to original sources

Avalanches and power-law behaviour in lung inflation.

When lungs are emptied during exhalation, peripheral airways close up. For people with lung disease, they may not reopen for a significant portion of inhalation, impairing gas exchange. A knowledge of the mechanisms that govern reinflation of collapsed regions of lungs is therefore central to the development of ventilation strategies for combating respiratory problems. Here we report measurements of the terminal airway resistance, Rt, during the opening of isolated dog lungs. When inflated by a constant flow, Rt decreases in discrete jumps. We find that the probability distribution of the sizes of the jumps and of the time intervals between them exhibit power-law behaviour over two decades. We develop a model of the inflation process in which 'avalanches' of airway openings are seen--with power-law distributions of both the size of avalanches and the time intervals between them--which agree quantitatively with those seen experimentally, and are reminiscent of the power-law behaviour observed for self-organized critical systems. Thus power-law distributions, arising from avalanches associated with threshold phenomena propagating down a branching tree structure, appear to govern the recruitment of terminal airspaces.

Airway Resistance↗

Influence of waveform and analysis technique on lung and chest wall properties.

To test an approach for measuring respiratory system resistance (R) and elastance (E) during non-sinusoidal forcing, we measured airway and esophageal pressures and flow at the trachea of 9 anesthetized-paralyzed dogs during sinusoidal forcing (SF) and 4 types of non-sinusoidal forcings at 0.15 and 0.6 Hz and 300 ml tidal volume. During SF, calculations of E and R of the lungs, chest wall or total system from discrete Fourier transform (DFT) and two other widely used methods (multiple regression and volume-pressure loop analysis) did not differ from each other (P > 0.05). During forcing with sinusoidal or step inspiration with passive expiration (inspiratory to expiratory ratio, I/E, = 1:1), Es from any analysis method were within 10% of values during SF. Although Rs of the lungs, chest wall or total system were not affected by waveform shape with DFT (P > 0.05), the other analysis methods gave values for R during non-SF that differed (P < 0.05) from those during SF by up to 77%. If I/E was changed to 1:2, with or without an added 10% inspiratory pause, values for E and R differed least from values during SF if DFT was used. During severe pulmonary edema induced by infusion of oleic acid in the right atrium, results for lung properties were similar to controls, despite large increases in E and R of the lungs. We conclude that E and R of the lungs and chest wall can be measured by DFT using nonsinusoidal forcing waveforms available on most clinical ventilators, incurring only modest error.

Airway Resistance↗

Oscillatory pressure-flow relationships of canine airways: a steady-state model for different gases.

We measured the airway pressure drop (delta Paw) between the trachea and the alveolus in three normal anesthetized paralyzed dogs, together with flow (V) at the trachea. Alveolar pressure was measured using a closed-chest modification of the standard alveolar capsule technique. Measurements were made during a period of sinusoidal ventilation at 0.83 Hz with a tidal volume of 35 ml/kg, after a 30-s period of apnea. We found that the amplitude of the swings in delta Paw decreased transiently after onset of sinusoidal ventilation. We established that this decrease was due to a reflex bronchodilatation by making additional measurements on vagotomized dogs. We developed a mathematical model to account for the steady-state data that included both laminar and turbulent flow, airway wall elastance, airway gas inertance, and the Bernoulli effect at the site of tracheal pressure measurement. The model accurately described the data obtained from each dog with four different gas mixtures containing air, helium, neon, and sulfur hexafluoride. We also constructed Moody plots from the measured delta Paw-V relationships, after removing the estimated contributions of gas inertance and the Bernoulli effect from delta Paw, and found evidence of the effects of changing airway dimensions throughout a breath, V unsteadiness, and differences between inspiratory and expiratory resistances.

Airway Resistance↗

Lung tissue viscoelasticity: a mathematical framework and its molecular basis.

Recent studies indicated that lung tissue stress relaxation is well represented by a simple empirical equation involving a power law, t-beta (where t is time). Likewise, tissue impedance is well described by a model having a frequency-independent (constant) phase with impedance proportional to omega-alpha (where omega is angular frequency and alpha is a constant). These models provide superior descriptions over conventional spring-dashpot systems. Here we offer a mathematical framework and explore its mechanistic basis for using the power law relaxation function and constant-phase impedance. We show that replacing ordinary time derivatives with fractional time derivatives in the constitutive equation of conventional spring-dashpot systems naturally leads to power law relaxation function, the Fourier transform of which is the constant-phase impedance with alpha = 1 - beta. We further establish that fractional derivatives have a mechanistic basis with respect to the viscoelasticity of certain polymer systems. This mechanistic basis arises from molecular theories that take into account the complexity and statistical nature of the system at the molecular level. Moreover, because tissues are composed of long flexible biopolymers, we argue that these molecular theories may also apply for soft tissues. In our approach a key parameter is the exponent beta, which is shown to be directly related to dynamic processes at the tissue fiber and matrix level. By exploring statistical properties of various polymer systems, we offer a molecular basis for several salient features of the dynamic passive mechanical properties of soft tissues.

Biomechanical Phenomena↗

Airway and tissue mechanics during physiological breathing and bronchoconstriction in dogs.

In five open-chest dogs and with four to five alveolar capsules we used an optimal ventilator waveform (OVW) to follow frequency and tidal volume (VT) dependence of lung, airway, and tissue resistance (R) and elastance (E) before and during constant infusion of histamine (16 micrograms.kg-1.min-1). OVW contains sufficient flow energy between 0.234 and 4.7 Hz, avoids nonlinear harmonic interactions, and simultaneously ventilates with physiological VT. Each OVW breath permits a smooth estimate of frequency dependence of R and E for the whole lung. A constant-phase model analysis provided estimates of purely viscous resistance (Rvis), which represents the sum of airway resistance (Raw) and any purely newtonian component of tissue resistance (Rti), and parameters G and H, which govern frequency dependence of Rti and tissue elastance (Eti), respectively. Tissue structural damping (eta) is calculated as G/H. This model was applied to the whole lung and tissue impedance as estimated from each capsule. We found a small but inconsequential purely newtonian component of Rti, even during constriction. Four dogs showed a peak response at approximately 4 min in lung Rvis coupled (in time) to initial increases in G, H, eta, and airway inhomogeneities. In two of these dogs the response was severe. Tissue properties estimated from whole lung impedance (G, H, and eta) were nearly identical to values estimated from unobstructed capsules throughout infusion. By using a technique independent of alveolar capsules, our results indicate that a major if not dominant response to a constrictive agonist occurs in lung tissues, resulting in a large increase in Rti and Eti. With severe constriction, significant increases occur in Raw and airway inhomogeneities as well. Finally, separation of airway and tissue properties using input impedance estimated from the frequency-rich OVW avoids use of alveolar capsules and may prove an effective tool for partitioning airway and tissue properties in humans.

Airway Resistance↗

Airway geometry and wall mechanical properties estimated from subglottal input impedance in humans.

We measured input impedance between 16 and 2,048 Hz in intubated subjects at functional residual capacity. The corresponding subglottal impedances (ZSG) were then computed using a model where the endotracheal tube was represented by a distributed-parameter two-port network. ZSG was well described by a model based on Horsfield's asymmetric airway geometry at total lung capacity (TLC) with nonrigid walls. The walls of the cartilaginous airways included separate cartilage and soft tissue compartments, whereas the noncartilaginous airway walls had only a soft tissue compartment. Both compartments consisted of a series resistance, inertance, and compliance, the values of which were computed from airway dimensions and wall material properties (viscosity, density, and Young's modulus). Airway wall thickness was determined by scaling an airway wall area-diameter relationship. Airway lengths and diameters were scaled from the Horsfield TLC values by a single factor and by an order-dependent sigmoidal curve, respectively. The estimated soft tissue viscosity and Young's modulus were 1.04 +/- 0.21 cmH2O.s and 593 +/- 319 cmH2O, respectively. Airway lengths and tracheal diameters were not statistically different from the Horsfield values. The estimated diameters of the more peripheral airways were significantly reduced compared with the Horsfield TLC values (e.g., approximately 40% at the terminal airway), which is consistent with the reduction in airway caliber when the lung deflates from TLC to functional residual capacity. These results indicate that high-frequency ZSG is sensitive to subglottal airway geometry and wall properties and that by use of appropriate structural models one can estimate airway geometry and airway wall parameters.

Adult↗

Serial distribution of airway mechanical properties in dogs: effects of histamine.

We measured respiratory input impedance (Zin; 8-2,048 Hz) in five dogs (anesthetized, tracheostomized, vagotomized, and mechanically ventilated) during 80 s of apnea after a bolus intravenous injection of saline or histamine (5.0 mg). In the control case, three antiresonances in Zin were found in four of the dogs, whereas in the remaining dog only two were found. The magnitude and frequency of these antiresonances were significantly altered after bronchoconstriction. To interpret Zin, a model incorporating detailed airway geometry, asymmetrical branching, and nonrigid airway walls was developed. The model fit both the saline and histamine Zin data well and predicted a serial distribution of bronchoconstriction consistent with known effects of histamine; i.e., the diameters of the most peripheral airways were reduced (26% of their control values), whereas tracheal diameters were not significantly affected. The model provided estimates of tracheal diameters that were well correlated (r = 0.92) with direct measurements. Control estimates of soft tissue viscosity (1.63 +/- 0.42 cmH2O.s) and Young's modulus (406 +/- 125 cmH2O) compared closely with values in the literature. These results indicate that bronchoconstriction induced by histamine results in significant changes in Zin over this frequency range and that by using this data analysis approach definitive physiological parameters relative to airway geometry and wall mechanical properties can be obtained from measurements made at the airway opening.

Airway Resistance↗

Nonlinear phenomena in respiratory mechanical measurements.

The impact of nonlinearities on the assessment of respiratory mechanics was examined using a block-structured model (BSM) featuring both flow (V) and tidal volume (VT) nonlinearities. The model consists of an airway compartment (AC) in series with a tissue compartment (TC). The AC is a series connection of a resistance, an inertance, and a nonlinear V-dependent element. The TC is composed of a linear Kelvin body in cascade with a nonlinear polynomial system. Analytic results show that 1) the lack of VT dependence using sine waves does not mean that the system is linear and 2) the hysteresivity (J. J. Fredberg and D. Stamenović. J. Appl. Physiol. 67:2408-2419, 1989) of a wide class of such tissue models is independent of VT, offering a simple mechanism for the coupling between resistance (R) and elastance (E). Furthermore, R from the step response of the TC was approximately 30% smaller than from sinusoids. Below 1 Hz, R and E of the BSM showed a negative VT dependence. Above 1 Hz, R increased with frequency and VT because of V dependence. Analysis of the response of the BSM to composite signals revealed how linear airway resistance can be overestimated because of V dependence and how tissue properties can be under-estimated because of harmonic distortion and cross talk induced by VT-associated nonlinearities.

Airway Resistance↗

Branching airway network models for analyzing high-frequency lung input impedance.

The input impedance of the lung (Zin) at high frequencies (> 100 Hz) is a complex function of the airway geometry and the mechanical properties of the airway walls. To investigate how the purely geometrical factors influence Zin, we measured Zin between 16 and 1,520 Hz in six dried dog lungs with the forced oscillation technique. In each of the lungs we found three resonances, at 36 +/- 5, 648 +/- 100, and 1,289 +/- 150 Hz, and at least two antiresonances (relative maxima in the real part of Zin), at 372 +/- 60 and 1,105 +/- 110 Hz. These data were fit with models featuring a detailed asymmetric branching network of the airways obtained from morphometric data published by Horsfield et al. (J. Appl. Physiol. 52: 21-26, 1982). On the basis of low-frequency (< 100 Hz) data alone, we first established a model of the acini, which was then attached to the end of the airway branching model. With a single scaling factor for the radius and length of the airways, the fit was unsatisfactory. Using sensitivity analysis techniques we determined which candidate variables of the structural model could influence Zin in a manner to improve the fit. We found that a two-parameter model accounting for separate central and peripheral airway diameter scaling provided a reasonable fit to Zin. On average the model required central diameter scaling close to unity (0.94 +/- 0.09), and the peripheral diameter scaling factor was 0.87 +/- 0.38. Over a range of parameter values that we believed were physiologically reasonable (i.e., scaling factors between 0.5 and 1.5), a single set of parameter values was found in all lungs. These results suggest that structurally based inverse models of Zin that include multiple antiresonances may provide information about airway geometry.

Airway Resistance↗

Optimal ventilation waveforms for estimating low-frequency respiratory impedance.

We present a broad-band optimal ventilator waveform (OVW), the concept of which was to create a computer-driven ventilator waveform containing increased energy at specific frequencies (f). Values of f were chosen such that nonlinear harmonic distortion and intermodulation were minimized. The phases at each f were then optimized such that the resulting flow waveform delivered sufficient volume to maintain gas exchange while minimizing peak-to-peak airway opening pressure. Simulations with a linear anatomically consistent branching airway model and a nonlinear viscoelastic model showed that respiratory resistance (Rrs) and elastance (Ers) estimates at 0.1-2 Hz from the OVW are far superior to those from a standard step ventilator waveform (SVW) during healthy and obstructed conditions and that the OVW reduces the influences of harmonic interactions. Using a servo-controlled oscillator, we applied individual sine waves, an OVW containing energy at 0.15625-2.4 Hz, and an SVW to healthy humans and one symptomatic asthmatic subject before and after bronchodilation. The OVW was markedly superior to the SVW and always provided smooth estimates of Rrs and Ers. Before bronchodilation in the asthmatic subject Rrs was highly elevated and Ers was markedly increased with f; after bronchodilation the level of Rrs and the f dependence of Ers decreased. Although based on results from only one asthmatic subject, these data suggest a dominant influence of airway constriction and lung inhomogeneities during asthmatic bronchoconstriction that is alleviated by bronchodilators. These and other results indicate that the OVW approach has high potential for simultaneously probing f and amplitude dependence in the mechanical properties of clinical subjects during physiological breathing conditions and perhaps during dynamic bronchoconstriction.

Adult↗

Effect of methacholine on low-frequency mechanics of canine airways and lung tissue.

We measured tracheal flow, tracheal pressure, and alveolar capsule pressure in four anesthetized paralyzed tracheostomized open-chest dogs. Lung impedance between 0.12 and 4.88 Hz was measured with a forced volume oscillation technique before and after the intravenous administration of methacholine (MCh). Before MCh administration, lung impedance was well described by a model featuring a single airway leading to an alveolar region surrounded by tissue with a continuous distribution of viscoelastic time constants as used by Hantos et al. (J. Appl. Physiol. 68: 849-860, 1990). After MCh, however, this model gave a poor fit to the impedances. The impedances were well accounted for, however, when the model was enhanced to include an extra time constant term, which we suspect is required to account for the uneven ventilation distribution produced by MCh. Airway impedance before MCh administration was well described by a simple resistance-inertance model, but a model incorporating serial inhomogeneity of ventilation was again required after MCh. Our results support those of previous studies indicating that the impedance of the normal dog lung is well described by a homogeneously ventilated viscoelastic tissue model. In contrast, our results after MCh administration show strong evidence of marked regional ventilation inhomogeneity in addition to the rheological properties of the tissues.

Airway Resistance↗

Low-frequency respiratory mechanics using ventilator-driven forced oscillations.

We evaluated the potential for using a fast Fourier transform (FFT) analysis applied to a standard ventilator waveform to estimate (< 2 Hz) frequency dependence of respiratory or lung resistance (R) and elastance (E). In four healthy humans we measured pressure and flow at the airway opening while applying sine wave forcing from 0.2 to 0.6 Hz at two tidal volumes (VT; 250 and 500 ml). We then applied a step inspiratory ventilator flow wave with relaxed expiration at the same VT and only 0.2 Hz. Step waveform data were also acquired from nine mechanically ventilated patients under intensive care unit conditions. Finally, we simultaneously measured total respiratory (rs), lung (L), and chest wall (cw) impedance data from two dogs (0.156-2 Hz) before and after severe pulmonary edema. Rrs and Ers were estimated by the FFT approach. Humans displayed a small frequency dependence in Rrs and Ers from 0.2 to 0.6 Hz, and both Rrs and Ers decreased at the higher VT. The spectral estimates of Rrs and Ers with the step ventilator wave were often qualitatively comparable to sine wave results below 0.6 Hz but became extremely erratic above the third harmonic. Conversely, in dogs the step wave produced reliable and stable estimates up to 2 Hz in all conditions. Nevertheless, Ecw and Ers still displayed clear and correlated oscillations with increasing frequency, whereas EL showed none. This suggests that nonlinear processes, most likely at the chest wall, contribute to periodic-like fluctuations in respiratory mechanical properties when estimated by applying FFT to a step ventilator wave. Moreover, in humans, but not dogs, a ventilator flow cycle contains insufficient signal energy beyond the third harmonic. We show that the amount of energy available at higher frequencies is largely governed by the mechanical time constant contributing to passive expiratory flow. In dogs the shorter time constant contributes to increased energy. In essence, the frequency content of the flow is subject dependent, and this is not a desirable situation for controlling the quality of the impedance spectra available from a standard ventilator wave.

Adult↗

Wave propagation, input impedance, and wall mechanics of the calf trachea from 16 to 1,600 Hz.

Propagation of waves in the airways is important in flow limitation as well as in oscillation mechanics. In five excised calf tracheae, we measured phase propagation velocity (c) and input impedance with open (Zop) or closed end (Zcl) for frequencies (f) between 16 and 1,600 Hz at two axial tensions [nonstretched (TN) and stretched (TS); TS > TN]. From 16 to 64 Hz, c slightly increased because of the viscoelastic properties of the wall tissues. Between 64 and 200 Hz, c was relatively constant and less than the free-field speed of sound (c0 = 340 m/s), with values smaller at TS (140 +/- 39 m/s) than at TN (172 +/- 35 m/s). Above 200 Hz, c exceeded c0 and displayed two maxima at approximately 300 and approximately 700 Hz, with values of approximately 360 and approximately 550 m/s, respectively. For f > 1,400 Hz, c approached c0. We provide evidence that the two maxima in c were the result of the two-compartment behavior of the wall tissues, i.e., the separate cartilaginous and soft tissues. A nonrigid tube model with its wall impedance composed of two series resistance, compliance, and inertance pathways in parallel simultaneously fits c, Zop, and Zcl well and hence provides a link among these data. By use of the relationship between volumetric wall parameters and the tracheal geometry, separate material properties such as viscosity and Young's modulus of both the soft tissue (approximately 1 cmH2O.s and approximately 0.26 x 10(4) cmH2O, respectively) and the cartilage (approximately 3.7 cmH2O.s and approximately 2 x 10(4) cmH2O, respectively) were estimated. These results indicate that measures of c and Zop or Zcl data over these frequencies provide information about the dynamic mechanical properties of both the soft tissue and cartilage in the airway walls.

Animals↗

Correcting for the Bernoulli effect in lateral pressure measurements.

Measurement of airway pressure is essential in the study of respiratory mechanics, and is usually done via a lateral tap in the conduit (e.g., endotracheal tube, cannula, or mouthpiece) leading into the subject's airway. Such pressure measurements, however, may be severely affected by the Bernoulli effect if the diameter of the conduit is small and the gas flow through it sufficiently high. We present in this note a simple method of assessing whether or not the Bernoulli effect is important in any particular situation. The technique involves comparing the pressure-flow relationships of the conduit obtained both by blowing air through it from one end and sucking air in the reverse direction by applying negative pressure at the same end. If the resistance of the conduit is the same for gas flow in both directions, then half the magnitude of the difference between the two pressure-flow relationships gives the magnitude of the Bernoulli effect pressure. We give results of an experimental situation in which this was the case. We also show that those conditions under which the Bernoulli effect is likely to be a problem are also those under which the velocity profile is likely to be approximately flat, thereby permitting the magnitude of the Bernoulli effect to be easily calculated.

Air Pressure↗

Viscoelastic properties of the visceral pleura and its contribution to lung impedance.

The mechanical impedances of 10 dog lung lobes (ZL) and circular pleura samples 1.6 cm in diameter (Zpl) were measured with small-amplitude forced oscillations between 0.2 and 4.2 Hz. Two to four samples were ablated from each lobe after their in situ tension had been fixed at 5 cmH2O transpulmonary pressure with plastic rings. Lobe resistance was inversely proportional to frequency (f) and lobe elastance increased linearly with the logarithm of f by 23%/decade. The real part of Zpl (Rpl) decreased hyperbolically with f. Pleural elastance (Epl) showed only a 5%/decade increase with log f. The regional variability of Epl was large and the data allowed the lumping of Epl into only two groups. The variability of Epl was higher in the group of Epl values from the coastal surfaces than in the group of Epl values from any other surfaces (3105 +/- 2741 (SD) vs 2263 +/- 1152 cm H2O/L). The mean intraindividual variation of Epl corresponding to costal and to other surfaces was 38 +/- 25 and 32 +/- 23%, respectively. The hysteresivity index (Fredberg and Stamenovic, J. Appl. Physiol., 67: 2408-2419, 1989) of the pleura was significantly smaller than that of the lobes (0.025 vs 0.148). Extrapolation of Zpl to the entire lobe surface predicted pleural/lobar resistance and elastance ratios of 2.7 +/- 0.4 and 16.8 +/- 10.6%, respectively, at 0.2 Hz, and 0.4 +/- 0.4 and 15.5 +/- 10.6%, respectively, at 4.2 Hz. This suggests that for small deformations and medium lung volumes the pleural contribution to ZL is almost ideally elastic and only slightly frequency-dependent.

Airway Resistance↗

Pseudorandom signals to estimate apparent transfer and coherence functions of nonlinear systems: applications to respiratory mechanics.

There is an increasing need in physiology to estimate nonparametric linear transfer functions from data originating from biological systems which are invariably nonlinear. For pseudorandom (PRN) input stimuli, we derive general expressions for the apparent transfer (Z) and coherence (gamma 2) functions of nonlinear systems that can be represented by a Volterra series. It is shown that in the case of PRN signals in which the frequency components are integer multiples of other components the estimates of Z are seriously biased due to harmonic distortion and crosstalk among frequency components of the input. When the PRN signal includes components that are not integer multiples of other components harmonic distortion is avoided, but not necessarily cross talk. Here the estimates of Z remain poor without a noticeable influence on gamma 2. To avoid the problems associated with harmonic distortions and minimize the influence of crosstalk, a family of pseudorandom signals is proposed which are especially suited for the estimation of Z and gamma 2 in mechanical measurements of physiological systems at low frequencies. The components in the signals cannot be reproduced as linear combinations of two or more frequency components of the input. In a second-order system, this completely eliminates the bias, while in higher-order, but not strongly nonlinear systems, the interactions among the components are reduced to a level that the response can be considered as if it was measured with independent sine waves of an equivalent amplitude. It is also shown that the values of gamma 2 are not appropriate to assess linearity of the system. The theory is supported by simulation results and experimental examples brought from the field of respiratory mechanics by comparing the input impedance of the respiratory system of a dog measured with various PRN signals.

Airway Resistance↗

Input impedance and peripheral inhomogeneity of dog lungs.

Tracheal pressure, central airflow, and alveolar capsule pressures in cardiac lobes were measured in open-chest dogs during 0.1- to 20-Hz pseudorandom forced oscillations applied at the airway opening. In the interval 0.1-4.15 Hz, the input impedance data were fitted by four-parameter models including frequency-independent airway resistance and inertance and tissue parts featuring a marked negative frequency dependence of resistance and a slight elevation of elastance with frequency. The models gave good fits both in the control state and during histamine infusion. At the same time, the regional transfer impedances (alveolar pressure-to-central airflow ratios) showed intralobar and interlobar variabilities of similar degrees, which increased with frequency and were exaggerated during histamine infusion. Results of simulation studies based on a lung model consisting of a central airway and a number of peripheral units with airway and tissue parameters that were given independent wide distributions were in agreement with the experimental findings and showed that even an extremely inhomogeneous lung structure can produce virtually homogeneous mechanical behavior at the input.

Airway Resistance↗

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.

Administration, Inhalation↗