Tracking of airway and tissue mechanics during TLC maneuvers in mice.

A tracking impedance estimation technique was developed to follow the changes in total respiratory impedance (Zrs) during slow total lung capacity maneuvers in six anesthetized and mechanically ventilated BALB/c mice. Zrs was measured with the wave-tube technique and pseudorandom forced oscillations at nine frequencies between 4 and 38 Hz during inflation from a transrespiratory pressure of 0-20 cmH2O and subsequent deflation, each lasting for approximately 20 s. Zrs was averaged for 0.125 s and fitted by a model featuring airway resistance (Raw) and inertance, and tissue damping and elastance (H). Lower airway conductance (Glaw) was linearly related to volume above functional residual capacity (V) between 0 and 75-95% maximum V, with a mean slope of dGlaw/dV = 13.6 +/- 4.6 cmH2O-1. s-1. The interdependence of Raw and H was characterized by two distinct and closely linear relationships for the low- and high-volume regions, separated at approximately 40% maximum V. Comparison of Raw with the highest-frequency resistance of the total respiratory system revealed a marked volume-dependent contribution of tissue resistance to total respiratory system resistance, resulting in the overestimation of Raw by 19 +/- 8 and 163 +/- 40% at functional residual capacity and total lung capacity, respectively, whereas the lowest frequency reactance was proportional to H; these findings indicate that single-frequency resistance values may become inappropriate as surrogates of Raw when tissue impedance is changing.     

Respiratory input impedance in anesthetized paralyzed patients

Respiratory impedance (Zrs) was measured between 0.25 and 32 Hz in seven anesthetized and paralyzed patients by applying forced oscillation of low amplitude at the inlet of the endotracheal tube. Effective respiratory resistance (Rrs; in cmH2O.l-1.s) fell sharply from 6.2 +/- 2.1 (SD) at 0.25 Hz to 2.3 +/- 0.6 at 2 Hz. From then on, Rrs decreased slightly with frequency down to 1.5 +/- 0.5 at 32 Hz. Respiratory reactance (Xrs; in cmH2O.l-1.s) was -22.2 +/- 5.9 at 0.25 Hz and reached zero at approximately 14 Hz and 2.3 +/- 0.8 at 32 Hz. Effective respiratory elastance (Ers = -2pi x frequency x Xrs; in cmH2O/1) was 34.8 +/- 9.2 at 0.25 Hz and increased markedly with frequency up to 44.2 +/- 8.6 at 2 Hz. We interpreted Zrs data in terms of a T network mechanical model. We represented the proximal branch by central airway resistance and inertance. The shunt pathway accounted for bronchial distensibility and alveolar gas compressibility. The distal branch included a Newtonian resistance component for tissues and peripheral airways and a viscoelastic component for tissues. When the viscoelastic component was represented by a Kelvin body as in the model of Bates et al. (J. Appl. Physiol. 61: 873-880, 1986), a good fit was obtained over the entire frequency range, and reasonable values of parameters were estimated. The strong frequency dependence of Rrs and Ers observed below 2 Hz in our anesthetized paralyzed patients could be mainly interpreted in terms of tissue viscoelasticity. Nevertheless, the high Ers we found with low volume excursions suggests that tissues also exhibit plasticlike properties.     

Broadband frequency dependence of respiratory impedance in rats.

Past studies in humans and other species have revealed the presence of resonances and antiresonances, i.e., minima and maxima in respiratory system impedance (Zrs), at frequencies much higher than those commonly employed in clinical applications of the forced oscillation technique (FOT). To help understand the mechanisms behind the first occurrence of antiresonance in the Zrs spectrum, the frequency response of the rat was studied by using FOT at both low and high frequencies. We measured Zrs in both Wistar and PVG/c rats using the wave tube technique, with a FOT signal ranging from 2 to 900 Hz. We then compared the high-frequency parameters, i.e., the first antiresonant frequency (far,1) and the resistive part of Zrs at that frequency [Rrs(far,1)], with parameters obtained by fitting a modified constant-phase model to low-frequency Zrs spectra. The far,1 was 570 +/- 43 (SD) Hz and 456 +/- 16 Hz in Wistar and PVG/c rats, respectively, and it did not shift with respiratory gases of different densities (air, heliox, and a mixture of SF(6)). The far,1 and Rrs(far,1) were relatively independent of methacholine-induced bronchoconstriction but changed significantly with increasing transrespiratory pressures up to 20 cmH(2)O, in the same way as airway resistance but independently of changes to tissue parameters. These results suggest that, unlike the human situation, the first antiresonance in the rat is not primarily dependent on the acoustic dimensions of the respiratory system and can be explained by interactions between compliances and inertances localized to the airways, but this most likely does not include airway wall compliance.     

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.     

Low-frequency respiratory mechanical impedance in the rat

A modified forced oscillatory technique was used to determine the respiratory mechanical impedances in anesthetized, paralyzed rats between 0.25 and 10 Hz. From the total respiratory (Zrs) and pulmonary impedance (ZL), measured with pseudorandom oscillations applied at the airway opening before and after thoracotomy, respectively, the chest wall impedance (ZW) was calculated as ZW = Zrs - ZL. The pulmonary (RL) and chest wall resistances were both markedly frequency dependent: between 0.25 and 2 Hz they contributed equally to the total resistance falling from 81.4 +/- 18.3 (SD) at 0.25 Hz to 27.1 +/- 1.7 kPa.l-1 X s at 2 Hz. The pulmonary compliance (CL) decreased mildly, from 2.78 +/- 0.44 at 0.25 Hz to 2.36 +/- 0.39 ml/kPa at 2 Hz, and then increased at higher frequencies, whereas the chest wall compliance declined monotonously from 4.19 +/- 0.88 at 0.25 Hz to 1.93 +/- 0.14 ml/kPa at 10 Hz. Although the frequency dependence of ZW can be interpreted on the basis of parallel inhomogeneities alone, the sharp fall in RL together with the relatively constant CL suggests that at low frequencies significant losses are imposed by the non-Newtonian resistive properties of the lung tissue.     

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)     

Respiratory impedance and multibreath N2 washout in healthy, asthmatic, and cystic fibrosis subjects

We measured forced expiratory volume in 1 s (FEV1), respiratory impedance (Zrs) from 4 to 60 Hz, and a multibreath N2 washout (MBNW) in 6 normal, 10 asthmatic, and 5 cystic fibrosis (CF) subjects. The MBNW were characterized by the mean dilution number (MDN) derived by a moment analysis. The Zrs spectra were characterized by the minimum resistance (Rmin), the drop in resistance (Rdrop) from 4 Hz to Rmin, and the first resonance frequency (Fr1). Measurements were repeated after bronchodilation in three normal and all asthmatic subjects. Before bronchodilation, six of the asthmatic subjects showed close to normal FEV1. The Zrs in the normal subjects showed low Rmin (1.9 +/- 0.7 cmH2O.l-1.s), Rdrop (0.4 +/- 0.4), and Fr1 (10 +/- 2 Hz). Four of the mildly obstructed asthmatic subjects had normal Zrs but elevated MDNs (i.e., abnormal ventilation distribution). The other six asthmatic subjects had significantly elevated Rmin (4.1 +/- 0.8), Rdrop (6.3 +/- 5.8), and Fr1 (34 +/- 0.4 Hz) and elevated MDNs. The CF patients had elevated Zrs features and MDNs. After bronchodilation, no changes in FEV1, MDN, or Zrs occurred in the normal subjects. All asthmatic subjects showed increased FEV1 and decreased MDN, but the Zrs was unaltered in the four asthmatic subjects whose base-line Zrs was normal. For the other six asthmatic subjects, there were large decreases in the Rmin, Rdrop, and Fr1. Finally, there was a poor correlation between the MDN and the Zrs features but high correlation between the Zrs features alone. These results imply that significant nonuniform peripheral airway obstruction can exist such that ventilation distribution is abnormal but Zrs from 4 to 60 Hz is not. Abnormalities in Zrs from 4 to 60 Hz occur only after significant overall obstruction in the peripheral and more central airways. Combining Zrs and the MBNW may permit us to infer whether the disease is predominantly in the lung periphery or in the more central airways.     

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.     

Lung and chest wall mechanics in rabbits during high-frequency body-surface oscillation

In eight anesthetized and tracheotomized rabbits, we studied the transfer impedances of the respiratory system during normocapnic ventilation by high-frequency body-surface oscillation from 3 to 15 Hz. The total respiratory impedance was partitioned into pulmonary and chest wall impedances to characterize the oscillatory mechanical properties of each component. The pulmonary and chest wall resistances were not frequency dependent in the 3- to 15-Hz range. The mean pulmonary resistance was 13.8 +/- 3.2 (SD) cmH2O.l-1.s, although the mean chest wall resistance was 8.6 +/- 2.0 cmH2O.l-1.s. The pulmonary elastance and inertance were 0.247 +/- 0.095 cmH2O/ml and 0.103 +/- 0.033 cmH2O.l-1.s2, respectively. The chest wall elastance and inertance were 0.533 +/- 0.136 cmH2O/ml and 0.041 +/- 0.063 cmH2O.l-1.s2, respectively. With a linear mechanical behavior, the transpulmonary pressure oscillations required to ventilate these tracheotomized animals were at their minimal value at 3 Hz. As the ventilatory frequency was increased beyond 6-9 Hz, both the minute ventilation necessary to maintain normocapnia and the pulmonary impedance increased. These data suggest that ventilation by body-surface oscillation is better suited for relatively moderate frequencies in rabbits with normal lungs.     

Partitioning of respiratory mechanics in halothane-anesthetized humans

In five spontaneously breathing anesthetized subjects [halothane approximately 1 minimal alveolar concentration (MAC), 70% N2O, 30% O2], flow, changes in lung volume, and esophageal and airway opening pressure were measured in order to partition the elastance (Ers) and flow resistance (Rrs) of the total respiratory system into the lung and chest wall components. Ers averaged (+/- SD) 23.0 +/- 4.9 cmH2O X l-1, while the corresponding values of pulmonary (EL) and chest wall (EW) elastance were 14.3 +/- 3.2 and 8.7 +/- 3.0 cmH2O X l-1, respectively. Intrinsic Rrs (upper airways excluded) averaged 2.3 +/- 0.2 cmH2O X l-1 X s, the corresponding values for pulmonary (RL) and chest wall (RW) flow resistance amounting to 0.8 +/- 0.4 and 1.5 +/- 0.5 cmH2O X l-1 X s, respectively. Ers increased relative to normal values in awake state, mainly reflecting increased EL. Rw was higher than previous estimates on awake seated subjects (approximately 1.0 cmH2O X l-1 X s). RL was relatively low, reflecting the fact that the subjects had received atropine (0.3-0.6 mg) and were breathing N2O. This is the first study in which both respiratory elastic and flow-resistive properties have been partitioned into lung and chest wall components in anesthetized humans.     

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.     

Mean airway pressure and mean alveolar pressure during high-frequency jet ventilation in rabbits

Mean airway pressure underestimates mean alveolar pressure during high-frequency oscillatory ventilation. We hypothesized that high inspiratory flows characteristic of high-frequency jet ventilation may generate greater inspiratory than expiratory pressure losses in the airways, thereby causing mean airway pressure to overestimate, rather than underestimate, mean alveolar pressure. To test this hypothesis, we ventilated anesthetized paralyzed rabbits with a jet ventilator at frequencies of 5, 10, and 15 Hz, constant inspiratory-to-expiratory time ratio of 0.5 and mean airway pressures of 5 and 10 cmH2O. We measured mean total airway pressure in the trachea with a modified Pitot probe, and we estimated mean alveolar pressure as the mean pressure corresponding in the static pressure-volume relationship to the mean volume of the respiratory system measured with a jacket plethysmograph. We found that mean airway pressure was similar to mean alveolar pressure at frequencies of 5 and 10 Hz but overestimated it by 1.1 and 1.4 cmH2O at mean airway pressures of 5 and 10 cmH2O, respectively, when frequency was increased to 15 Hz. We attribute this finding primarily to the combined effect of nonlinear pressure frictional losses in the airways and higher inspiratory than expiratory flows. Despite the nonlinearity of the pressure-flow relationship, inspiratory and expiratory net pressure losses decreased with respect to mean inspiratory and expiratory flows at the higher rates, suggesting rate dependence of flow distribution. Redistribution of tidal volume to a shunt airway compliance is thought to occur at high frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Production mechanism of crackles in excised normal canine lungs

Lung crackles may be produced by the opening of small airways or by the sudden expansion of alveoli. We studied the generation of crackles in excised canine lobes ventilated in an airtight box. Total airflow, transairway pressure (Pta), transpulmonary pressure (Ptp), and crackles were recorded simultaneously. Crackles were produced only during inflation and had high-peak frequencies (738 +/- 194 Hz, mean +/- SD). During inflation, crackles were produced from 111 +/- 83 ms (mean +/- SD) prior to the negative peak of Pta, presumably when small airways began to open. When end-expiratory Ptp was set constant between 15 and 20 cmH2O and end-expiratory Ptp was gradually reduced from 5 cmH2O to -15 or -20 cmH2O in a breath-by-breath manner, crackles were produced in the cycles in which end-expiratory Ptp fell below -1 to 1 cmH2O. This pressure was consistent with previously known airway closing pressures. When end-expiratory Ptp was set constant at -10 cmH2O and end inspiratory Ptp was gradually increased from -5 to 15 or 20 cmH2O, crackles were produced in inspiratory phase in which end-inspiratory Ptp exceeded 4-6 cmH2O. This pressure was consistent with previously known airway opening pressures. These results indicate that crackles in excised normal dog lungs are produced by opening of peripheral airways and are not generated by the sudden inflation of groups of alveoli.     

Stress adaptation and low-frequency impedance of rat lungs

At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of CO2 rebreathing on pulmonary mechanics in premature infants

The effects of hypercapnia produced by CO2 rebreathing on total pulmonary, supraglottic, and lower airway (larynx and lungs) resistance were determined in eight premature infants [gestational age at birth 32 +/- 3 (SE) wk, weight at study 1,950 +/- 150 g]. Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a fluid-filled or 5-Fr Millar pressure catheter. Trials of hyperoxic (40% inspired O2 fraction) CO2 rebreathing were performed during quiet sleep. Total pulmonary resistance decreased progressively as end-tidal PCO2 (PETCO2) increased from 63 +/- 23 to 23 +/- 15 cmH2O.l-1.s in inspiration and from 115 +/- 82 to 42 +/- 27 cmH2O.l-1.s in expiration between room air (PETCO2 37 Torr) and PETCO2 of 55 Torr (P less than 0.05). Lower airway resistance (larynx and lungs) also decreased from 52 +/- 22 to 18 +/- 14 cmH2O.l-1.s in inspiration and from 88 +/- 45 to 30 +/- 22 cmH2O.l-1.s in expiration between PETCO2 of 37 and 55 Torr, respectively (P less than 0.05). Resistance of the supraglottic airway also decreased during inspiration from 7.2 +/- 2.5 to 3.6 +/- 2.5 cmH2O.l-1.s and in expiration from 7.6 +/- 3.3 to 5.3 +/- 4.7 cmH2O.l-1.s at PETCO2 of 37 and 55 Torr (P less than 0.05). The decrease in resistance that occurs within the airway in response to inhaled CO2 may permit greater airflow at any level of respiratory drive, thereby improving the infant's response to CO2.     

Human respiratory input impedance from 4 to 200 Hz: physiological and modeling considerations

Recent studies on respiratory impedance (Zrs) have predicted that at frequencies greater than 64 Hz a second resonance will occur. Furthermore, if one intends to fit a model more complicated than the simple series combination of a resistance, inertance, and compliance to Zrs data, the only way to ensure statistically reliable parameter estimates is to include data surrounding this second resonance. An additional question, however, is whether the resulting parameters are physiologically meaningful. We obtained input impedance data from eight healthy adult humans using discrete frequency forced oscillations from 4 to 200 Hz. Three resonant frequencies were seen: 8 +/- 2, 151 +/- 10, and 182 +/- 16 Hz. A seven-parameter lumped element model provided an excellent fit to the data in all subjects. This model consists of an airway resistance (Raw), which is linearly dependent on frequency, and airway inertance separated from a tissue resistance, inertance, and compliance by a shunt compliance (Cg) thought to represent gas compressibility. Model estimates of Raw and Cg were compared with those suggested by measurement of Raw and thoracic gas volume using a plethysmograph. In all subjects the model Raw and Cg were significantly lower than and not correlated with the corresponding plethysmographic measurement. We hypothesize that the statistically reliable but physiologically inconsistent parameters are a consequence of the distorting influence of airway wall compliance and/or airway quarter-wave resonance. Such factors are not inherent to the seven-parameter model.     

Respiratory mechanics during halothane anesthesia and anesthesia-paralysis in humans

In six spontaneously breathing anesthetized subjects [halothane approximately 1 maximum anesthetic concentration (MAC), 70% N2O-30% O2], we measured flow (V), volume (V), and tracheal pressure (Ptr). With airway occluded at end-inspiration tidal volume (VT), we measured Ptr when the subjects relaxed the respiratory muscles. Dividing relaxed Ptr by VT, total respiratory system elastance (Ers) was obtained. With the subject still relaxed, the occlusion was released to obtain the V-V relationship during the ensuing relaxed expiration. Under these conditions, the expiratory driving pressure is V X Ers, and thus the pressure-flow relationship of the system can be obtained. By subtracting the flow resistance of equipment, the intrinsic respiratory flow resistance (Rrs) is obtained. Similar measurements were repeated during anesthesia-paralysis (succinylcholine). Ers averaged 23.9 +/- 4 (+/- SD) during anesthesia and 21 +/- 1.8 cmH2O X 1(-1) during anesthesia-paralysis. The corresponding values of intrinsic Rrs were 1.6 +/- 0.7 and 1.9 +/- 0.9 cmH2O X 1(-1) X s, respectively. These results indicate that Ers increases substantially during anesthesia, whereas Rrs remains within the normal limits. Muscle paralysis has no significant effect on Ers and Rrs. We also provide the first measurements of inspiratory muscle activity and related negative work during spontaneous expiration in anesthetized humans. These show that 36-74% of the elastic energy stored during inspiration is wasted in terms of negative inspiratory muscle work.     

Reassessment of the interruption technique for measuring flow resistance in humans

We have previously produced evidence that, in patients with obstructive lung disease, compliance of extrathoracic airways is responsible for lack of mouth-to-alveolar pressure equilibration during respiratory efforts against a closed airway. The flow interruption method for measuring respiratory resistance (Rint) is potentially faced with the same problems. We reassessed the merits of the interruption technique by rendering the extrathoracic airways more rigid and by using a rapid shutter. We measured airway resistance (Raw) with whole body plethysmography during panting (at 2 Hz) and Rint during quiet breathing. Rint and Raw were expressed as specific airway (sGaw) and interruptive conductance (sGint), respectively. In nine healthy subjects (cheeks supported), sGint (0.140 +/- 0.050 s-1.cmH2O-1) was lower (P less than 0.02) than sGaw (0.182 +/- 0.043 s-1.cmH2O-1). By contrast, in 12 patients with severe obstructive lung disease (forced expiratory volume in 1 s/vital capacity = 41.0 +/- 19.8%), sGint (0.058 +/- 0.012 s-1.cmH2O-1) was higher (P less than 0.05) than sGaw (0.047 +/- 0.007 s-1.cmH2O-1), when the cheeks were supported. When the mouth floor was also supported, average values of sGaw (0.048 +/- 0.008 s-1.cmH2O-1) and sGint (0.049 +/- 0.014 s-1.cmH2O-1) became similar. In conclusion, we confirm previous findings in healthy subjects of higher values of Rint, with respect to Raw, probably because of differences in glottis opening between quiet breathing and panting. In airflow obstruction, supporting both the cheeks and the mouth floor decreased sGint, which became similar to sGaw.     

Augmentation of parasympathetic contraction in tracheal and bronchial airways by PGF2 alpha in situ

We studied the effect of exogenous prostaglandin F2 alpha (PGF2 alpha) on airway smooth muscle contraction caused by parasympathetic stimulation in 22 mongrel dogs in situ. Voltage (0-30 V, constant 20 Hz) and frequency-response (0-25 Hz, 25 V) curves were generated by stimulating the cut ends of both cervical vagus nerves. Airway response was measured isometrically as active tension (AT) in a segment of cervical trachea and as change in airway resistance (RL) and dynamic compliance (Cdyn) in bronchial airways. One hour after 5 mg/kg iv indomethacin, a cumulative frequency-response curve was generated in nine animals by electrical stimulation of the vagus nerves at 15-s intervals. Reproducibility was demonstrated by generating a second curve 7 min later. A third frequency-response curve was generated during active contraction of the airway caused by continuous intravenous infusion of 10 micrograms X kg-1 X min-1PPGF2 alpha. Additional frequency-response studies were generated 15 and 30 min after PGF2 alpha, when airway contractile response (delta RL = +2.8 +/- 0.65 cmH2O X 1(-1) X s; delta Cdyn = -0.0259 +/- 0.007 1/cmH2O) returned to base line. Substantial augmentation of AT, RL, and Cdyn responses was demonstrated in every animal studied (P less than 0.01 for all points greater than 8 Hz) 15 min after PGF2 alpha. At 30 min, response did not differ from initial base-line control. In four animals receiving sham infusion, all frequency-response curves were identical. We demonstrate that PGF2 alpha augments the response to vagus nerve stimulation in tracheal and bronchial airways. Augmentation does not depend on PGF2 alpha-induced active tone.