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.     

Density dependence of respiratory input and transfer impedances in humans

Total respiratory input (Zin) and transfer (Ztr) impedances were obtained from 4 to 30 Hz in 10 healthy subjects breathing air and He-O2. Zin was measured by applying pressure oscillations around the head to minimize the upper airway shunt and Ztr by applying pressure oscillations around the chest. Ztr was analyzed with a six-coefficient model featuring airways resistance (Raw) and inertance (Iaw), alveolar gas compressibility, and tissue resistance, inertance, and compliance. Breathing He-O2 significantly decreased Raw (1.35 +/- 0.32 vs. 1.74 +/- 0.49 cmH2O.l-1.s in air, P less than 0.01) and Iaw (0.59 +/- 0.33 vs. 1.90 +/- 0.44 x 10(-2) cmH2O.l-1.s2), but, as expected, it did not change the tissue coefficients significantly. Airways impedance was also separately computed by combining Zin and Ztr data. This approach demonstrated similar variations in Raw and Iaw with the lighter gas mixture. With both analyses, however, the changes in Iaw were more than what was expected from the change in density. This indicates that factors other than gas inertance are included in Iaw and reveals the short-comings of the six-coefficient model to interpret impedance data.     

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.

     

Inverse modeling of dog airway and respiratory system impedances

Mechanical parameters of the respiratory system are often estimated from respiratory impedances using lumped-element inverse models. One such six-element model is composed of an airway branch [with a resistance (Raw) and inertance (Iaw)] separated from a tissue branch [with a resistance (Rt), inertance (It), and compliance (Ct)] by a shunt compliance representing alveolar gas compression (Cg). Even though the airways are known to have frequency-dependent resistance and inertance, these inverse models have been composed of linear frequency-independent elements. In this study we investigated the use of inverse models where the airway branch was represented by a frequency-independent Raw and Iaw, a Raw that is linearly related to frequency and an Iaw that is independent of frequency, and a system of identical parallel tubes the impedance of which was computed from the tube radius and length. These inverse models were used to analyze airway and respiratory impedances between 2 and 1,024 Hz that were predicted from an anatomically detailed forward model. The forward model represented the airways by an asymmetrically branched network with a terminal impedance representative of known Cg, Rt, It, and Ct. For respiratory impedances between 2 and 128 Hz, all models fit the data reasonably well, and reasonably accurate estimates of Cg, Rt, It, and Ct were extracted from these data. For data above 200 Hz, however, only the multiple-tube model accurately fitted respiratory impedances (Zrs). This model fitted the Zrs data best when composed of 27 tubes, each having a radius of 0.148 cm and a length of 16.5 cm.     

Airways impedance during single breaths of foreign gases.

The changes in airways resistance (Raw) and inertance (Iaw) during single inspirations of pure methane, helium, neon, and ethane at a flow of 0.1 l/s were measured in six healthy subjects by use of a forced-oscillation technique. Raw and Iaw were computed from respiratory transfer impedance obtained at a frequency of 20 Hz by applying pressure oscillations at the chest and measuring flow at the mouth with a bag-in-box system. Compared with the air data, the changes of Iaw after inhalation of 500 ml of gas averaged -41.1% with methane, -82.8% with helium, -25.8% with neon, and +4.8% with ethane. These changes were slightly less than the changes in gas density (-45%, -86%, -31%, and +5%, respectively). The inhaled volumes at which 50% of the changes had occurred (V50) did not differ significantly among gases and were approximately 100 ml. For Raw the data were more noisy than for Iaw; they were discarded in two subjects because of a strong and irreproducible volume dependence in air. Consistent differences were seen between the remaining subjects, one of whom exhibited a predominant viscosity dependence of Raw, one a predominant density dependence, and two an intermediate pattern. V50s were larger for Raw than for Iaw, indicating a more peripheral distribution of Raw. For Raw, V50s were lower with helium than with methane, in agreement with the notion that density-dependent resistance is located mainly in the large airways. The results suggest that some information on the serial distribution of Raw and Iaw may be derived from impedance measurements with foreign gases.     

Density dependence of respiratory system impedances between 5 and 320 Hz in humans

For respiratory system impedance (Zrs), the six-element model of DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956) suggests three resonant frequencies (f1,f2,f3), where f1 is the result of the sum of tissue and airway inertances and tissue compliance and f2 is the result of alveolar gas compression compliance (Cg) and tissue inertance (Iti). Three such resonant frequencies have been reported in humans. However, the parameter estimates resulting from fitting this model to the data suggested that f2 and f3 were not associated with Cg and Iti but with airway acoustic properties. In the present study, we measured Zrs between 5 and 320 Hz in 10 healthy adult humans breathing room air or 80% He-20% O2 (HeO2) to gain insight as to whether airway or tissue properties are responsible for the f2 and f3. When the subjects breathed room air, f2 occurred at 170 +/- 16 (SD) Hz, and when they breathed HeO2 it occurred at 240 +/- 24 Hz. If this resonance were due to Cg and Iti it should not have been affected to this extent by the breathing of HeO2. We thus conclude that f2 is not due to tissue elements but that it is an airway acoustic resonance. Furthermore, application of the six-element model to analyze Zrs data at these frequencies is inappropriate, and models incorporating the airway acoustic properties should be used. One such model is based on the concept of equivalent length, which is defined as the length of an open-ended, cylindrical tube that has the same fundamental acoustic resonant frequency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency response of the chest: modeling and parameter estimation.

The frequency response of the respiratory system was studied in the range from 3 to 70 Hz in 15 normal subjects by applying sinusoidal pressure variations around the chest and measuring gas flow at the mouth. The observed input-output relationships were systematically compared to those predicted on the basis of linear differential equations of increasing order. From 3 to 20 Hz the behavior of the system was best described by a 3rd-order equation, and from 3 to 50 Hz by a 4th-order one. A mechanistic model of the 4th order, featuring tissue compliance (Ct), resistance (Rt) and inertance (It), alveolar gas compressibility (Cg) and airway resistance (Raw), and inertance (Iaw) was developed. Using that model, the following mean values were found: Ct = 2.08-10(-2)1-hPa-1 (1 hPa congruent to 1 cm of water); Rt = 1.10-hPa-1(-1)-s; It = 0.21-10(-2)hPa-1(-1)-s2; Raw = 1.35-hPa-1(-1)-s; Iaw = 2.55-10(-2)hPa-1(-1)-s2. Additional experiments devised to validate the model were reasonably successful, suggesting that the physical meaning attributed to the coefficients was correct. The validity of the assumptions and the physiological meaning of the coefficients are discussed.     

Maturational changes in responses of tissue and airway resistance to histamine

Dreshaj, Ismail A., Musa A. Haxhiu, Charles F. Potter, FatonH. Agani, and Richard J. Martin. Maturational changes in responsesof tissue and airway resistance to histamine. J. Appl.Physiol. 81(4): 1785-1791, 1996.We determinedhow postnatal maturation affects the relative contributions of airwaysand lung parenchyma to pulmonary resistance(RL) and whether there are developmental differences in their respective responses to constrictive agents. We studied open-chest ventilated anesthetized piglets of threeages: 2-4 days, 2-3 wk, and 10 wk.RL was partitioned into tissue(Rti) and airway (Raw) resistance by means of alveolar capsules underbaseline conditions and after intravenous histamine. Postnatalmaturation was associated with a progressive decline inRL, Rti, and Raw and with anincrease in the contribution of Rti toRL from 38 ± 8% at 2-4days to 72 ± 2% at both 2-3 and 10 wk. Histamine causedRL to increase at all ages. Whenpartitioned into Rti and Raw, the percent increase in Rti significantlyexceeded that of Raw at both 2-4 days and 2-3 wk. Incontrast, the percent increase in Raw significantly exceeded that ofRti at 10 wk. Administration of atropine before histamine in pigletsaged 10 wk reduced the response of Rti and Raw to histamine.Histamine-induced responses ofRL were blocked by priorH₁-receptor blockade withpyrilamine (2 mg/kg). These results indicate that1) the contribution of Rti and Rawto RL changes during maturationand that 2) contractile responses toexogenous histamine are manifest predominantly in most distal airwaysand lung parenchyma during early postnatal life; with advancingmaturation there is greater contribution of airways to the increase inRL induced by histamine.

     

Respiratory transfer impedances with pressure input at the mouth and chest

Two methods of measuring respiratory transfer impedance (Ztr) were compared in 14 normal subjects, from 4 to 30 Hz, 1) studying the relationship between transrespiratory pressure (Prs) and flow at the chest when varying pressure at the mouth (Ztrm) and 2) studying the relationship between Prs and flow at the mouth when varying pressure around the chest wall (Ztrw). The similarity of the two relationships was expected on the basis of a T-network model. Almost identical phase responses were obtained from the two methods. Pressure-flow ratios were slightly larger for Ztrw than for Ztrm, but differences did not exceed 2% on average in 11 of 14 subjects. When the data were analyzed with the six-coefficient model proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), similar values were found for tissue compliance and tissue inertance but slightly different values for gaseous inertance in the airways (1.97 +/- 0.35 X 10(-2) cmH2O X l-1 X s2 for Ztrw vs. 1.73 +/- 0.26 for Ztrm; P less than 0.01). Similar results were also found for total respiratory resistance but with a slightly larger contribution of airway resistance for Ztrw (64 +/- 14 vs. 57 +/- 10%; P less than 0.05). As a practical conclusion it is recommended to measure Ztrw, which is technically much easier.     

Physiological basis for resonant frequencies in respiratory system impedances in dogs

The lumped six-element model of the respiratory system proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956) has often been used to analyze respiratory system impedance (Zrs) data. This model predicts a resonance (relative minimum in Zrs) at fr between 6 and 10 Hz and an antiresonance (relative maximum in Zrs) at far at higher frequencies (greater than 64 Hz). The far is due to the lumped tissue inertance (Iti) and the alveolar gas compression compliance (Cg). An fr and far have been recently reported in humans, but the far was shown to be not related to Iti and Cg, but instead it is the first acoustic antiresonance of the airways due to their axial dimensions). Zrs data to frequencies high enough to include the far have not been reported in dogs. In this study, we measured Zrs in dogs for frequencies between 5 and 320 Hz and found an fr at 7.5 +/- 1.6 Hz and two far at 97 +/- 13 and 231 +/- 27 Hz (far,1 and far,2, respectively). When breathing 80% He-20% O2, the fr shifted to 14 +/- 2 Hz, far,1 did not change (98 +/- 9 Hz), and far,2 increased to greater than 320 Hz. The behavior of fr and far,1 is consistent with the structure-function implied by the six-element model. However, the presence of an far,2 is not consistent with this model, because it is the airway acoustic antiresonance not represented in the model. These results indicate that, for frequencies that include the fr and far,1, the six-element model can be used to analyze Zrs data and reliable estimates of the model's parameters can be extracted by fitting the model to the data. However, more complex models must be used to analyze Zrs data that include far,2.     

Reliability of parameter estimates from models applied to respiratory impedance data

Many previous studies have fit lumped parameter models to respiratory input (Zin) and transfer (Ztr) impedance data. For frequency ranges higher than 4-32 Hz, a six-element model may be required in which an airway branch (with a resistance and inertance) is separated from a tissue branch (with a resistance, inertance, and compliance) by a shunt compliance. A sensitivity analysis is applied to predict the effects of frequency range on the accuracy of parameter estimates in this model obtained from Zin or Ztr data. Using a parameter set estimated from experimental data between 4 and 64 Hz in dogs, both Zin and Ztr were simulated from 4 to 200 Hz. Impedance sensitivity to each parameter was also calculated over this frequency range. The simulation predicted that for Zin a second resonance occurs near 80 Hz and that the impedance is considerably more sensitive to several of the parameters at frequencies surrounding this resonance than at any other frequencies. Also, unless data is obtained at very high frequencies (where the model is suspect), Zin data provides more accurate estimates than Ztr data. After adding random noise to the simulated Zin data, we attempted to extract the original parameters by using a nonlinear regression applied to three frequency ranges: 4-32, 4-64, and 4-110 Hz. Estimated parameters were substantially incorrect when using only 4- to 32-Hz or 4- to 64-Hz data, but nearly correct when fitting 4- to 110-Hz data. These results indicate that respiratory system parameters can be more accurately extracted from Zin than Ztr, and to make physiological inferences from parameter estimates based on Zin impedance data in dogs, the data must include frequencies surrounding the second resonance.     

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.

     

Effects of heterogeneities on the partitioning of airway and tissue properties in normal mice.

We measured the mechanical properties of the respiratory system of C57BL/6 mice using the optimal ventilation waveform method in closed- and open-chest conditions at different positive end-expiratory pressures. The tissue damping (G), tissue elastance (H), airway resistance (Raw), and hysteresivity were obtained by fitting the impedance data to three different models: a constant-phase model by Hantos et al. (Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ. J Appl Physiol 72: 168-178, 1992), a heterogeneous Raw model by Suki et al. (Suki B, Yuan H, Zhang Q, Lutchen KR. J Appl Physiol 82: 1349-1359, 1997), and a heterogeneous H model by Ito et al. (Ito S, Ingenito EP, Arold SP, Parameswaran H, Tgavalekos NT, Lutchen KR, Suki B. J Appl Physiol 97: 204-212, 2004). Both in the closed- and open-chest conditions, G and hysteresivity were the lowest and Raw the highest in the heterogeneous Raw model, and G and H were the largest in the heterogeneous H model. Values of G, Raw, and hysteresivity were significantly higher in the closed-chest than in the open-chest condition. However, H was not affected by the conditions. When the tidal volume of the optimal ventilation waveform was decreased from 8 to 4 ml/kg in the closed-chest condition, G and hysteresivity significantly increased, but there were smaller changes in H or Raw. In summary, values of the obtained mechanical properties varied among these models, primarily due to heterogeneity. Moreover, the mechanical parameters were significantly affected by the chest wall and tidal volume in mice. Contribution of the chest wall and heterogeneity to the mechanical properties should be carefully considered in physiological studies in which partitioning of airway and tissue properties are attempted.     

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.     

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.     

Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats.

We investigated the effects of a selective beta(2)-agonist, salbutamol, and of phosphodiesterase type 4 inhibition with 4-(3-butoxy-4-methoxy benzyl)-2-imidazolidinone (Ro-20-1724) on the airway and parenchymal mechanics during steady-state constriction induced by MCh administered as an aerosol or intravenously (iv). The wave-tube technique was used to measure the lung input impedance (ZL) between 0.5 and 20 Hz in 31 anesthetized, paralyzed, open-chest adult Brown Norway rats. To separate the airway and parenchymal responses, a model containing an airway resistance (Raw) and inertance (Iaw), and a parenchymal damping (G) and elastance (H), was fitted to ZL spectra under control conditions, during steady-state constriction, and after either salbutamol or Ro-20-1724 delivery. In the Brown Norway rat, the response to iv MCh infusion was seen in Raw and G, whereas continuous aerosolized MCh challenge produced increases in G and H only. Both salbutamol, administered either as an aerosol or iv, and Ro-20-1724 significantly reversed the increases in Raw and G when MCh was administered iv. During the MCh aerosol challenge, Ro-20-1724 significantly reversed the increases in G and H, whereas salbutamol had no effect. These results suggest that, after MCh-induced changes in lung function, salbutamol increases the airway caliber. Ro-20-1724 is effective in reversing the airway narrowings, and it may also decrease the parenchymal constriction.     

Inability to separate airway from tissue properties by use of human respiratory input impedance

Respiratory input impedance (Zrs) from 2.5 to 320 Hz displays a high-frequency resonance, the location of which depends on the density of the resident gas in the lungs (J. Appl. Physiol. 67: 2323-2330, 1989). A previously used six-element model has suggested that the resonance is due to alveolar gas compression (Cg) resonating with tissue inertance (Iti). However, the density dependence of the resonance indicates that is associated with the first airway acoustic resonance. The goal of this study was to determine whether unique properties for tissues and airways can be extracted from Zrs data by use of models that incorporate airway acoustic phenomena. We applied several models incorporating airway acoustics to the 2.5- to 320-Hz data from nine healthy adult humans during room air (RA) and 20% He-80% O2 (HeO2) breathing. A model consisting of a single open-ended rigid tube produced a resonance far sharper than that seen in the data. To dampen the resonance features, we used a model of multiple open-ended rigid tubes in parallel. This model fit the data very well for both RA and HeO2 but required fewer and longer tubes with HeO2. Another way to dampen the resonance was to use a single rigid tube terminated with an alveolar-tissue unit. This model also fit the data well, but the alveolar Cg estimates were far smaller than those expected based on the subject's thoracic gas volume. If Cg was fixed based on the thoracic gas volume, a large number of tubes were again required. These results along with additional simulations show that from input Zrs alone one cannot uniquely identify features indigenous to alveolar Cg or to the respiratory tissues.     

Respiratory transfer impedance and derived mechanical properties of conscious rats.

A setup is described for measuring the respiratory transfer impedance of conscious rats in the frequency range 16-208 Hz. The rats were placed in a restraining tube in which head and body were separated by means of a dough neck collar. The restraining tube was placed in a body chamber, allowing the application of pseudorandom noise pressure variations to the chest and abdomen. The flow at the airway opening was measured in a small chamber connected to the body chamber. The short-term reproducibility of the transfer impedance was tested by repeated measurements in nine Wistar rats. The mean coefficient of variation for the impedance did not exceed 10%. The impedance data were analyzed using different models of the respiratory system of which a three-coefficient resistance-inertance-compliance model provided the most reliable estimates of respiratory resistance (Rrs) and inertance (Irs). The model response, however, departed systematically from the measured impedance. A nine-coefficient model best described the data. Optimization of this model provided estimates of the respiratory tissue coefficients and upper and lower airway coefficients. Rrs with this model was 13.6 +/- 1.0 (SD) kPa.l-1.s, Irs was 14.5 +/- 1.3 Pa.l-1.s2, and tissue compliance (Cti) was 2.5 +/- 0.5 ml/kPa. The intraindividual coefficient of variation for Rrs and Irs was 11 and 18%, respectively. Because most of the resistance and inertance was located in the airways (85 and 81% of Rrs and Irs, respectively), the partitioning in tissue and upper and lower airway components was rather poor. Our values for Rrs and Irs of conscious rats were much lower and our values for Cti were higher than previously reported values for anesthetized rats.     

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.     

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.