A new method to measure nasal impedance in spontaneously breathing adults

As an alternative to standard rhinomanometric methods, we applied forced oscillations at the mouth in five normal subjects and determined their nasal impedance with a novel method involving flow subtraction. Pressure oscillations of constant amplitude were applied at the mouth of a subject both when the nostrils were open and when they were closed with a noseclip. The airflows measured under the two conditions were subtracted to yield the oscillating nasal airflow at the imposed pressure. The resultant pressure-flow relation defined the nasal impedance of the subject. For frequencies between 3 and 15 Hz, the transnasal pressure-flow relation was well described by a linear lumped parameter model consisting of a resistive and inertial element. Nasal resistance obtained with flow subtraction did not differ significantly from control measurements obtained while the subjects performed the Valsalva maneuver. In contrast, nasal inertance obtained with flow subtraction was approximately twice that obtained with the Valsalva method. The difference between inertances may reflect structural changes in nasopharyngeal dimensions that occur with the Valsalva maneuver. We conclude that the mechanical impedance of the nasal passage may be determined during spontaneous breathing from the response to imposed forced oscillations at the mouth. The noninvasive nature of this method suggests that it may be simpler to implement than traditional rhinomanometric methods.     

Effect of cardiogenic oscillations on gas mixing during tracheal insufflation of oxygen

In a previous study using tracheal insufflation of O2 (TRIO) at a rate of 2 l/min, we showed that anesthetized paralyzed dogs could be adequately oxygenated for up to 5 h, albeit with hypercapnia (mean arterial PCO2 approximately 160 Torr). To examine the contribution of cardiogenic oscillations in producing this gas exchange, we studied seven anesthetized paralyzed dogs weighing between 19.6 and 25.5 kg and quantified gas transport by analyzing continuous N2-washout curves in vivo and postmortem. We found that cardiogenic oscillations increase gas mixing roughly fourfold and that this value was independent of insufflation flow rate (0.2-10.0 l/min). Our results lend indirect evidence that, with regard to gas exchange, there are two mechanistically different zones in the lung during TRIO. One zone, located in the more peripheral areas of the lung, is dominated by the effects of cardiac oscillations and molecular diffusion and accounts for the increase in gas mixing found in the alive vs. dead dog. A second zone, close to the insufflated jet of O2, uses convective streaming to produce greater gas mixing at higher flows.     

A modified measurement of respiratory resistance by forced oscillation during normal breathing.

We have modified the measurements of the resistance of the respiratory system, Rrs, by the forced oscillation technique and we have developed equipment to automatically compute Rrs. Flow rate and mouth pressure are treated by selective averaging filters that remove the interference of the subject's respiratory flow on the imposed oscillations. The filtered mean Rrs represents a weighted ensemble average computer over both inspiration and expiration. This method avoids aberrant Rrs values, decreases the variability, and yields an unbiased mean Rrs. Rrs may be measured during slow or rapid spontaneous breathing, in normals and in obstructive patients, over a range of 3-9 Hz. A good reproducibility of Rrs at several days' interval was demonstrated. Frequency dependence of Rrs was found in patients with obstructive lung disease but not in healthy nonsmokers.     

Lymph flow from edematous dog lungs

We measured the flow rate (QLV) from cannulated lung lymph vessels in anesthetized dogs. Low-resistance lymph cannulas were used and the vessels were cannulated at the lung hilus. When we increased left atrial pressure to 42.9 +/- 5.7 (SD) cmH2O (base line = 6.6 +/- 4.6 cmH2O), the lungs became edematous and QLV increased from a base line of 20.4 +/- 21.5 microliters/min to 388 +/- 185 microliters/min. QLV plateaued at the higher level. We also measured the relationship between lymph flow rate and the height of the outflow end of the lymph cannula. From this relationship, determined at the end of the period of elevated left atrial pressure, we calculated the effective resistance and pressure driving lymph from the lungs. We also cannulated lymph vessels in the downstream direction and estimated the effective resistance and pressure opposing flow into the part of the lymphatic system between the lung hilus and the veins (extrapulmonary lymph vessels). We found that the effective resistance of the extrapulmonary part of the lymph system (0.042 +/- 0.030 (SD) cmH2O X min X microliter-1) was large compared with the resistance of the lymph vessels from the lungs (0.026 +/- 0.027). These data indicate that the resistance of the extrapulmonary part of the lung lymph system limits the maximum flow of lymph from edematous lungs.     

Effect of positive airway pressure on capillary transit time in rabbit lung

We used fluorescence videomicroscopy to measure the passage of fluorescent dye through the subpleural microcirculation of the lung. With the rabbit in the left lateral decubitus position, the subpleural microcirculation was viewed either through a transparent parietal pleural window located in the superior part of the chest or directly with the chest open. There was no physical contact with the chest or lung. The rabbit was anesthetized, paralyzed, and mechanically ventilated with 100% O2. The dye was injected into the right ventricle during a 2-min apneic period to eliminate lung movement due to ventilation. The video signal of the passage of the dye was analyzed frame by frame by use of digital image processing to compensate for cardiogenic oscillations of the lung surface. Gray scale levels of an arteriole and adjacent venule were measured every 1/30 s. Capillary transit time was determined from the difference between the concentration-weighted mean time values of the arteriolar and venular dye dilution curves. We studied the effect of airway pressure (0-20 cmH2O) on transit time. Cardiac output was measured at different airway pressures by the thermal dilution technique. Capillary transit time averaged 0.60 s at functional residual capacity. Right ventricular-to-arteriolar transit time was four times as large as the capillary transit time. An increase in airway pressure from 0-5 to 20 cmH2O resulted in a fourfold increase in both capillary and arterial transit times and a threefold decrease in cardiac output.     

Pattern of simulated snoring is different through mouth and nose

Cineradiography of the pharynx during simulated snoring was done in 6 healthy volunteers, and supraglottic pressure and flow rate were recorded in 12 others. We observed, immediately before snoring, a decrease in the sagittal diameter of the oropharynx followed, during snoring, by high-frequency oscillations of soft palate and pharyngeal walls. The pattern of soft palate oscillations was different while snoring through the nose or mouth. During inspiratory snoring through the nose, the soft palate remained in close contact with the back of the tongue and only the uvula presented high-frequency oscillations. Snoring through the mouth resulted in ample high-frequency oscillations of the whole soft palate. Frequency of airflow and supraglottic pressure oscillations was less (P less than 0.05) during mouth (28.2 +/- 7.5 Hz) than during nasal snoring (77.8 +/- 36.7 Hz). This difference may be related to the smaller oscillating mass (i.e., uvula) during nasal snoring. At variance with our previous data, which showed that snoring during sleep, in both heavy (nonapneic) snorers and obstructive sleep apnea patients, was systematically preceded by flow limitation, this was not true during simulated snoring.     

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.     

Role of additive stochastic modulation of the heart activity in the formation of 0.1-Hz blood flow oscillations in the human cardiovascular system

In the framework of our previous hypothesis about the participation of structural and hydrodynamic properties of the vascular bed in the formation of the 0.1-Hz component of blood flow oscillations in the human cardiovascular system and on the basis of the reduced hydrodynamic model, the role of additive stochastic perturbations of the operation of the single-chamber pump that simulates the heart was investigated. It was shown that aperiodic noise modulation of the rigidity of the walls of the pump or its valves generates low-frequency oscillations of pressure and blood flow velocity of arterial vascular bed with the maximum amplitude at a frequency close to 0.1 Hz.     

Influence of inspiratory flow rate and frequency on O2 cost of resistive breathing in humans

We examined the combined effect of an increase in inspiratory flow rate and frequency on the O2 cost of inspiratory resistive breathing (VO2 resp). In each of three to six pairs of runs we measured VO2 resp in six normal subjects breathing through an inspiratory resistance with a constant tidal volume (VT). One of each pair of runs was performed at an inspiratory muscle contraction frequency of approximately 10/min and the other at approximately 30/min. Inspiratory mouth pressure was 45 +/- 2% (SE) of maximum at the lower contraction frequency and 43 +/- 2% at the higher frequency. Duty cycle (the ratio of contraction time to total cycle time) was constant at 0.51 +/- 0.01. However, during the higher frequency runs, two of every three contractions were against an occluded airway. Because VT and duty cycle were kept constant, mean inspiratory flow rate increased with frequency. Careful selection of appropriate parameters allowed the pairs of runs to be matched both for work rate and pressure-time product. The VO2 resp did not increase, despite approximately threefold increases in both inspiratory flow rate and contraction frequency. On the contrary, there was a trend toward lower values for VO2 resp during the higher frequency runs. Because these were performed at a slightly lower mean lung volume, a second study was designed to measure the VO2 resp of generating the same inspiratory pressure (45% maximum static inspiratory mouth pressure at functional residual capacity) at the same frequency but at two different lung volumes. This was achieved with a negligibly small work rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interrupter resistance elucidated by alveolar pressure measurement in open-chest normal dogs

The interrupter method for measuring respiratory system resistance involves rapidly interrupting flow at the mouth while measuring the pressure just distal to the point of interruption. The pressure signal observed invariably exhibits two distinct phases. The first phase is a very rapid jump, designated delta Pinit, which occurs immediately on interruption of flow. The second phase is designated delta Pdif and is a further pressure change in the same direction as delta Pinit but evolving over several seconds. The physiological interpretations of delta Pinit and delta Pdif have been somewhat unclear. Delta Pinit has been taken to equal the pressure drop across the pulmonary airways, possibly with a contribution from the tissues of the respiratory system. Delta Pdif can arise, in principle, from two sources: gas redistribution throughout the lung after interruption of flow and stress recovery within the tissues. To resolve these issues we performed interruption experiments on anesthetized paralyzed, tracheotomized, open-chest normal dogs during passive expiration while measuring alveolar pressures at three sites with alveolar capsules. We found that, in the absence of the chest wall, delta Pinit reflects only the resistance of the airways and that delta Pdif can be ascribed almost entirely to the stress recovery properties of lung tissues.     

Cardiogenic oscillations in He and SF6 expirograms during airway and venous loading

Cardiogenic oscillations in the expired partial pressure profiles of two inert gases (He and SF6) were monitored in seven anesthetized paralyzed mechanically ventilated dogs. He and SF6 were administered either intravenously by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)] or by washin into lung gas [airway loading (AL)]. The single-breath expirograms obtained during constant-flow expiration after inspiration of test gas-free air displayed distinct and regular cardiogenic oscillations. The relative oscillation amplitude (ROA), calculated as oscillation amplitude divided by mixed expired-inspired partial pressure difference, was in the range of 1-8%. The ROA for both He and SF6 was approximately 4.2 times higher in VL than in AL, which indicated that among lung units that emptied sequentially in the cardiac cycle, the effects of alveolar ventilation-perfusion (VA/Q) inequality were more pronounced than those of alveolar ventilation-alveolar volume (VA/VA) inequality. In AL, He and SF6 oscillations were 180 degrees out of phase compared with CO2 and O2 oscillations and with He and SF6 oscillations in VL, which suggests that regions with low VA/VA had high VA/Q and very low Q/VA. The ROA was practically unaffected by breath holding in both AL and VL, which indicates that there was little diffusive or convective (cardiogenic) mixing between the lung units that were responsible for cardiogenic oscillations. The ROA was consistently higher for He than for SF6, and the He-to-SF6 ratio was independent of route of test gas loading, averaging 1.6 in both AL and VL. This result may be explained by laminar Taylor dispersion, whereby oscillations generated in peripheral lung regions are dissipated in inverse proportion to diffusion coefficient during transit through the proximal (larger) airways.     

Regional expiratory flow limitation studied with Technegas in asthma.

Regional expiratory flow limitation (EFL) may occur during tidal breathing without being detected by measurements of flow at the mouth. We tested this hypothesis by using Technegas to reveal sites of EFL. A first study (study 1) was undertaken to determine whether deposition of Technegas during tidal breathing reveals the occurrence of regional EFL in induced bronchoconstriction. Time-activity curves of Technegas inhaled during 12 tidal breaths were measured in four asthmatic subjects at control conditions and after exposure to inhaled methacholine at a dose sufficient to abolish expiratory flow reserve near functional residual capacity. A second study (study 2) was conducted in seven asthmatic subjects at control and after three increasing doses of methacholine to compare the pattern of Technegas deposition in the lung with the occurrence of EFL. The latter was assessed at the mouth by comparing tidal with forced expiratory flow or with the flow generated on application of a negative pressure. Study 1 documented enhanced and spotty deposition of Technegas in the central lung regions with increasing radioactivity during tidal expiration. This is consistent with increased impaction of Technegas on the airway wall downstream from the flow-limiting segment. Study 2 showed that both methods based on analysis of flow at the mouth failed to detect EFL at the time spotty deposition of Technegas occurred. We conclude that regional EFL occurs asynchronously across the lung and that methods based on mouth flow measurements are insensitive to it.     

Relative hysteresis of the airways and lung parenchyma in normal subjects

We evaluated the mechanical properties of the airways sequentially from the glottis toward the main bronchi in 10 normal subjects. Plots of airway cross-sectional area vs. lung volume, measured during inspiration and expiration, were used to determine the relative magnitude of the airways vs. parenchymal hysteresis. Airway cross-sectional area was measured by means of the acoustic reflection technique. We found that the hysteresis of the proximal part of the trachea was greater than that of the lung parenchyma, whereas the hysteresis of the distal trachea and subcarinal segments of the airways was smaller than that of the lung parenchyma. The transition zone between the proximal and the more distal airway properties occurred 8-26 cm distal to the glottis. This transition zone was reproducible in its location on repeated testing in each subject but varied among subjects. To the extent that relative hysteresis of the airways depends on bronchomotor tone, our findings suggest that the bronchomotor tone is inhomogeneous, being maximal at the proximal part of the trachea and gradually decreasing toward the more distal trachea and subcarinal airway segments.     

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.     

Effect of catheter size on pressures recorded in small pulmonary veins in dog lung.

Controversy continues about the contribution of the veins to pulmonary vascular resistance. From data obtained in studies using intravascular catheters, it appears that a major fraction (up to 44%) of the total pulmonary vascular pressure drop resides in larger (greater than 1.0 mm diam) veins, whereas micropuncture data and various models give much less pressure drop. Theoretically, artifactual pressure drops can be obtained if an intravascular catheter partly obstructs the vessel. We made measurements of pressure in the same lung vein with two different-sized catheters (1.2 and 0.6 mm OD, respectively). In paired experiments the larger catheter always measured a higher pressure than the smaller one, except close to the large lobar vein outlet. In some of the experiments we measured the diameter of the vessel containing the indwelling catheter by freezing the lung and then serial-sectioned the frozen lung. From these data we could infer that the range of vein diameter in the which the smaller catheter measured a lower pressure was 1.5-4 mm. We conclude that the larger catheter overestimated the pressure because of greater obstruction. The pressures obtained with the smaller catheter suggest that little (less than 10%) of the total pulmonary vascular resistance resides in veins larger than approximately 1 mm diam under zone 3 baseline conditions.     

Measurement of thoracic gas volume by low-frequency ambient pressure changes

When the whole body is exposed to sinusoidal variations of ambient pressure (delta Pam) at very low frequencies (f), the resulting compression and expansion of alveolar gas is almost entirely achieved by gas flow through the airways (Vaw). As a consequence thoracic gas volume (TGV) may be computed from the imaginary part (Im) of the delta Pam/Vaw relationship: TGV = PB/[2 pi f X Im(delta Pam/Vaw)], where PB is barometric minus alveolar water vapor pressure. The method was tested in 35 normal subjects and compared with body plethysmography. The subjects sat in a chamber connected to a large-stroke-volume reciprocating pump that brought about pressure swings of 40 cmH2O at 0.05 Hz. delta Pam and Vaw were digitally processed by fast Fourier transform to extract the low-frequency component from the much larger respiratory flow. Total lung capacities (TLC) obtained by ambient pressure changes and by plethylsmography were highly correlated (r = 0.959, p less than 0.001) and not significantly different (6.96 +/- 1.38 l vs. 6.99 +/- 1.38). TLC obtained by ambient pressure changes were not influenced by lowering the frequency to 0.03 Hz, adding an external resistance at the mouth, or increasing abdominal gas volume. We conclude that the method is practical and in agreement with body plethysmography in normal subjects.     

Human respiratory input impedance between 32and 800Hz, measured by interrupter technique and forced oscillations

Frey, Urs, Bela Suki, Richard Kraemer, and Andrew C. Jackson. Human respiratory input impedance between 32 and 800 Hz,measured by interrupter technique and forced oscillations. J. Appl. Physiol. 82(3):1018-1023, 1997.Respiratory input impedance (Zin) over a widerange of frequencies (f) has beenshown to be useful in determining airway resistance (Raw) and tissueresistance in dogs or airway wall properties in human adults. Zinmeasurements are noninvasive and, therefore, potentially useful ininvestigation of airway mechanics in infants. However, accuratemeasurements of Zin at these f valueswith the use of forced oscillatory techniques (FOT) in infants aredifficult because of their relatively high Raw and large compliance ofthe face mask. If pseudorandom noise pressure oscillations generated bya loudspeaker are applied at the airway opening (FOT), the power of theresulting flow decreases inversely withf because of capacitive shunting intothe volume of the gas in the speaker chamber and in the face mask. Westudied whether high-frequency respiratory Zin can be measured by using rapid flow interruption [high-speed interrupter technique(HIT)], in which we expect the flow amplitude in the respiratorysystem to be higher than in the FOT. We compared Zin measured by HIT with Zin measured by FOT in a dried dog lung and in five healthy adultsubjects. The impedance was calculated from two pressure signalsmeasured between the mouth and the HIT valve. The impedance could beassessed from 32 to 800 Hz. Its real part at lowf as well as thef and amplitude of the first andsecond acoustic resonance, measured by FOT and by HIT, were notsignificantly different. The power spectrum of oscillatory flow whenthe HIT was used showed amplitudes that were at least 100 times greaterthan those when FOT was used, increasing atf > 400 Hz. In conclusion,the HIT enables the measurement of high-frequency Zin data ranging from 32 to 800 Hz with particularly high flow amplitudes and, therefore, possibly better signal-to-noise ratio. This is particularly important in systems with high Raw, e.g., in infants, when measurements have tobe performed through a face mask.

     

Constant-flow ventilation in pigs

Constant-flow ventilation (CFV) is a ventilatory technique in which physiological blood gases can be maintained in dogs by a constant flow of fresh gas introduced via two catheters placed in the main-stem bronchi (J. Appl. Physiol. 53: 483-489, 1982). High-velocity gas exiting from the catheters can create uneven pressure differences in adjacent lung segments, and these pressure differences could lead to gas flow through collateral channels. To examine this hypothesis, we studied CFV in pigs, animals known to have a high resistance to collateral ventilation. In three pigs we examined steady-state gas exchange, and in six others we studied unsteady gas exchange at three flow rates (20, 35, and 50 l/min) and three catheter positions (0.5, 1.5, and 2.5 cm distal to the tracheal carina). During steady-state runs we were unable to attain normocapnia; the arterial CO2 partial pressure (PaCO2) was approximately 300 Torr at all flow rates and all catheter positions, compared with 20-50 Torr at similar flows and positions in dogs studied previously. The initial unsteady gas-exchange experiments indicated no consistent effect of catheter position or flow rate on the rate of rise of PaCO2. In three other pigs, the rates of rise of PaCO2 were compared with the rates observed with apneic oxygenation (AO). At the maximum flow and deepest position, the rate of rise of PaCO2 was lower during CFV than during AO. These data suggest that flow through collateral channels might be important in producing adequate gas transport during CFV; however, other factors such as airway morphometry and the effects of cardiogenic oscillations may explain the differences between the results in pigs and dogs.     

Airway stability and heterogeneity in the constricted lung.

The effect of bronchoconstriction on airway resistance is known to be spatially heterogeneous and dependent on tidal volume. We present a model of a single terminal airway that explains these features. The model describes a feedback between flow and airway resistance mediated by parenchymal interdependence and the mechanics of activated smooth muscle. The pressure-tidal volume relationship for a constricted terminal airway is computed and shown to be sigmoidal. Constricted terminal airways are predicted to have two stable states: one effectively open and one nearly closed. We argue that the heterogeneity of whole lung constriction is a consequence of this behavior. Airways are partitioned between the two states to accommodate total flow, and changes in tidal volume and end-expiratory pressure affect the number of airways in each state. Quantitative predictions for whole lung resistance and elastance agree with data from previously published studies on lung impedance.     

A new technique to demonstrate flow limitation in partial expiratory flow-volume curves in infants

Partial expiratory flow-volume (PEFV) curves in infants are generated by applying a compressive pressure over the chest wall with an inflatable jacket. This study addresses two issues: pressure transmission to and across the chest wall and whether flow limitation can be identified. Eleven infants sedated with chloral hydrate were studied. Pressure transmission to the chest wall, measured with neonatal blood pressure cuffs placed on the infant's body surface, was 72 +/- 4% of jacket pressure during compression maneuvers. The pressure transmission to the air spaces, determined by measuring airway pressure during a compression maneuver against an occluded airway, was 56 +/- 6% of jacket pressure. A significant amount of the applied pressure is therefore lost across both the jacket and chest wall. Rapid pressure oscillations (RPO) were superimposed on static jacket pressures while expiratory flow was measured. Absence of associated oscillations of flow measured at the mouth was taken to indicate that flow was independent of driving pressure and therefore limited. Flow limitation was demonstrable with the RPO technique in all infants for jacket pressures greater than 50 cmH2O; however, it was evident at jacket pressures less than 30 cmH2O jacket pressure in four infants with obstructive airway disease. The RPO technique is a useful adjunct to the compression maneuver utilized to generate PEFV curves in infants because it facilitates the recognition of expiratory flow limitation.