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

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

Dependence of central airway resistance on frequency and tidal volume: a model study

The resistance of a hollow cast of human central airways was measured during true sinusoidal airflow oscillations over a wide range of frequencies (0.5-40 Hz) and for various flow amplitudes up to 8 l/s. Pressure and flow were measured in the trachea with high-performance transducers, digitized and averaged over 100 cycles. Data were studied at two points in the flow cycle: at peak inspiratory and expiratory flows and in the two neighborhoods around zero flow where airway resistance (Rv approximately equal to o) was taken as the average slope of the pressure-flow (P-V) curve in each zone. When data obtained near peak flow were plotted in terms of dimensionless pressure drop vs. peak Reynolds number (Rem) and compared with steady-state data, we found no difference up to 2 Hz as previously reported (Isabey and Chang, J. Appl. Physiol. 51: 1338-1348, 1981), a slight decay in pressure drop between 4 and 8 Hz, a frequency-dependent increase in peak flow resistance at high frequencies (10-40 Hz) governed by the Strouhal number alpha 2/Rem beyond alpha 2/Rem = 0.5. On the other hand RV approximately equal to o was found to increase relative to steady state as local acceleration increases, e.g., as peak flow increases at a fixed frequency; this differs from the classical linear theory of oscillatory flow in a long straight tube. To explain these results, we had to use, as in our previous study, an alternative expression for the Strouhal number, i.e., epsilon = L X A X (dV/dt)/V2 (where L and A are the length and cross-sectional area of the trachea and V is a constant flow range over which resistance around flow reversal was computed), which accurately reflects the ratio of local acceleration [d(V/A)/dt)] to convective acceleration [(V/A)2/L] in developing branching flow. Finally, to delineate the regions of dominance of each of the dimensionless parameters, we compiled frequency-tidal volume diagrams for peak flows as well as for reversal. Epsilon, which is negligible near peak flows, appeared to govern the oscillatory P-V relationship near flow reversal in a transitional region of the diagram located between regions of steadiness, or moderate unsteadiness, and a region of dominant unsteadiness governed by alpha.     

Partitioning of pulmonary resistance in calves

Nine right apical lobes of healthy Friesian calves and 10 right apical lobes of double-muscled calves of Belgian White and Blue (BWB) breed were suspended in an airtight box, inflated at a constant transpulmonary pressure (Ptp), and subjected to quasi-sinusoidal pressure changes (amplitude: 0.5 kPa) at a frequency of 30 cycles/min. Lobar resistance (RL) was partitioned at six different lung volumes into three components: central airway resistance (Rc), small airway resistance (Rp), and tissue resistance (Rt). Pressure in small airways (2-3 mm ID) was measured with a retrograde catheter. Alveolar pressure was sampled in capsules glued onto the punctured pleural surface. RL was minimal at values of Ptp comprised between 0.5 and 0.7 kPa and increased at higher and lower values of Ptp. At a Ptp of 0.5 kPa, Rc, Rp, and Rt represented 30, 15, and 55% of RL, respectively, in Friesian calves and 25, 25, and 50% in BWB calves. Rp increased markedly at low lung volumes. Rt was responsible for the increase of RL at high Ptp. Rc tended to decrease at high Ptp. The significantly higher values of Rp in BWB calves (P less than 0.05) might explain the sensitivity of this breed to severe bronchopneumonia.     

Expiratory muscle contribution to tidal volume in head-up dogs

A change from the supine to the head-up posture in anesthetized dogs elicits increased phasic expiratory activation of the rib cage and abdominal expiratory muscles. However, when this postural change is produced over a 4- to 5-s period, there is an initial apnea during which all the muscles are silent. In the present studies, we have taken advantage of this initial silence to determine functional residual capacity (FRC) and measure the subsequent change in end-expiratory lung volume. Eight animals were studied, and in all of them end-expiratory lung volume in the head-up posture decreased relative to FRC [329 +/- 70 (SE) ml]. Because this decrease also represents the increase in lung volume as a result of expiratory muscle relaxation at the end of the expiratory pause, it can be used to determine the expiratory muscle contribution to tidal volume (VT). The average contribution was 62 +/- 6% VT. After denervation of the rib cage expiratory muscles, the reduction in end-expiratory lung volume still amounted to 273 +/- 84 ml (49 +/- 10% VT). Thus, in head-up dogs, about two-thirds of VT result from the action of the expiratory muscles, and most of it (83%) is due to the action of the abdominal rather than the rib cage expiratory muscles.     

Ventilation heterogeneity in excised lobes: effect of tidal volume.

Although several factors are known to influence nonuniformity of ventilation, including lung mechanical properties (regional structure and compliance), external factors (chest wall, pleural pressure, heart), and ventilatory parameters (tidal and preinspiratory volume, flow rate), their relative contributions are poorly understood. We studied five excised, unperfused, canine right-middle lobes under varied levels of tidal volume (VT), thus eliminating many factors affecting heterogeneity. Multiple-breath washouts of N(2) were analyzed for anatomic dead space volume (VD(anat)), nonuniformity of N(2) washout, and nonuniformity between joined acinar regions vs. that occurring between larger joined regions. Approximately 80% of ventilation heterogeneity was found among joined acinar regions at resting levels of VT, but increasing VT reduced intra-acinar heterogeneity to about 25% of that found at resting levels. Increasing VT had essentially no effect on VD(anat) and heterogeneity among larger joined regions. The results indicate that the magnitude of VT is a major influence on the dominant intra-acinar component of ventilation heterogeneity and that VT effects on VD(anat) are likely due to perfusion and/or influences normally external to the lobar structure.     

Effects of tidal volume and methacholine on low-frequency total respiratory impedance in dogs

The frequency dependence of respiratory impedance (Zrs) from 0.125 to 4 Hz (Hantos et al., J. Appl. Physiol. 60: 123-132, 1986) may reflect inhomogeneous parallel time constants or the inherent viscoelastic properties of the respiratory tissues. However, studies on the lung alone or chest wall alone indicate that their impedance features are also dependent on the tidal volumes (VT) of the forced oscillations. The goals of this study were 1) to identify how total Zrs at lower frequencies measured with random noise (RN) compared with that measure with larger VT, 2) to identify how Zrs measured with RN is affected by bronchoconstriction, and 3) to identify the impact of using linear models for analyzing such data. We measured Zrs in six healthy dogs by use of a RN technique from 0.125 to 4 Hz or with a ventilator from 0.125 to 0.75 Hz with VT from 50 to 250 ml. Then methacholine was administered and the RN was repeated. Two linear models were fit to each separate set of data. Both models assume uniform airways leading to viscoelastic tissues. For healthy dogs, the respiratory resistance (Rrs) decreased with frequency, with most of the decrease occurring from 0.125 to 0.375 Hz. Significant VT dependence of Rrs was seen only at these lower frequencies, with Rrs higher as VT decreased. The respiratory compliance (Crs) was dependent on VT in a similar fashion at all frequencies, with Crs decreasing as VT decreased. Both linear models fit the data well at all VT, but the viscoelastic parameters of each model were very sensitive to VT. After methacholine, the minimum Rrs increased as did the total drop with frequency. Nevertheless the same models fit the data well, and both the airways and tissue parameters were altered after methacholine. We conclude that inferences based only on low-frequency Zrs data are problematic because of the effects of VT on such data (and subsequent linear modeling of it) and the apparent inability of such data to differentiate parallel inhomogeneities from normal viscoelastic properties of the respiratory tissues.     

Lung and chest wall impedances in the dog: effects of frequency and tidal volume.

Dependences of the mechanical properties of the respiratory system on frequency (f) and tidal volume (VT) in the normal ranges of breathing are not clear. We measured, simultaneously and in vivo, resistance and elastance of the total respiratory system (Rrs and Ers), lungs (RL and EL), and chest wall (Rcw and Ecw) of five healthy anesthetized paralyzed dogs during sinusoidal volume oscillations at the trachea (50-300 ml, 0.2-2 Hz) delivered at a constant mean lung volume. Each dog showed the same f and VT dependences. The Ers and Ecw increased with increasing f to 1 Hz and decreased with increasing VT up to 200 ml. Although EL increased slightly with increasing f, it was independent of VT. The Rcw decreased from 0.2 to 2 Hz at all VT and decreased with increasing VT. Although the RL decreased from 0.2 to 0.6 Hz and was independent of VT, at higher f RL tended to increase with increasing f and VT (i.e., as peak flow increased). Finally, the f and VT dependences of Rrs were similar to those of Rcw below 0.6 Hz but mirrored RL at higher f. These data capture the competing influences of airflow nonlinearities vs. tissue nonlinearities on f and VT dependence of the lung, chest wall, and total respiratory system. More specifically, we conclude that 1) VT dependences in Ers and Rrs below 0.6 Hz are due to nonlinearities in chest wall properties, 2) above 0.6 Hz, the flow dependence of airways resistance dominates RL and Rrs, and 3) lung tissue behavior is linear in the normal range of breathing.     

Effect of tidal volume and frequency on the temporal fall in lung compliance

In this study we have investigated how changes in respiratory frequency and tidal volume in anesthetized dogs affect the fall in dynamic compliance (Cdyn) that occurs with time after a hyperinflation. Results showed that increasing frequency [at controlled arterial (PaCO2)] PCO2 from 16 to 32 breaths/min had no effect on either the rate of fall or the magnitude of the fall up to 1 h after the hyperinflation. However, increasing the tidal volume from 300 to 750 ml abolished the fall in Cdyn from 10 to 50 min after the hyperinflation; the fall within the first 10 min remained unchanged. We also examined the effect of a simulated "hyperinflation" on the compliance of strips of parenchymal tissue in vitro. This result indicated that in the absence of surface forces, parenchymal tissue demonstrates a fall in compliance, which is complete within 10 min. Overall our findings are consistent with the hypothesis that the fall in Cdyn after hyperinflation is a two-phase process. The initial rapid fall in Cdyn (i.e., within 10 min) may simply represent a passive recovery process from the hyperinflation stress on the parenchymal tissue. The slower fall occurring after 10 min likely results from progressive increases in surface tension, and this increase can apparently be blocked by increases in tidal volume.     

Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits

Shen, X., S. J. Gunst, and R. S. Tepper. Effect oftidal volume and frequency on airway responsiveness in mechanically ventilated rabbits. J. Appl. Physiol.83(4): 1202-1208, 1997.We evaluated the effects of the rate andvolume of tidal ventilation on airway resistance (Raw) duringintravenous methacholine (MCh) challenge in mechanically ventilatedrabbits. Five rabbits were challenged at tidal volumes of 5, 10, and 20 ml/kg at a frequency of 15 breaths/min and also under static conditions(0 ml/kg tidal volume). Four rabbits were subjected to MCh challenge atfrequencies of 6 and 30 breaths/min with a tidal volume of 10 ml/kg andalso under static conditions. In both groups, the increase in Raw with MCh challenge was significantly greater under static conditions thanduring tidal ventilation at any frequency or volume. Increases in thevolume or frequency of tidal ventilation resulted in significant decreases in Raw in response to MCh. We conclude that tidal breathing suppresses airway responsiveness in rabbits in vivo. The suppression ofnarrowing in response to MCh increases as the magnitude of the volumeor the frequency of the tidal oscillations is increased. Our findingssuggest that the effect of lung volume changes on airway responsivenessin vivo is primarily related to the stretch of airway smooth muscle.

     

Partitioning of nasal and pulmonary resistance changes during noninvasive plethysmography in mice

Double-chamber plethysmography is a well established noninvasive method of assessing airflow obstruction in small lab animals. It allows measurement of the specific airway resistance (sRaw), which unlike enhanced pause (Penh), is a meaningful airway mechanics parameter. Since sRaw is measured in spontaneously breathing mice, a limitation of the method is the inability to exclude nasal resistance changes. We recently showed that mice are not truly obligate nasal breathers and that after nasal occlusion, nasally breathing mice can transition to an oral mode of breathing. We now show that it is experimentally possible to algebraically separate the average nasal and pulmonary (including laryngeal) components of total airway resistance change by a series of measurements made across groups of mice breathing nasally or orally, assuming that oral resistance remains constant. Using this approach, we show that nasal resistance change comprises one-half or more of the total resistance change during methacholine challenge. Inhibition of mucin secretion from airway goblet cells attenuates pulmonary but not nasal airway hyperresponsiveness (AHR), and nasal AHR in a murine model of rhinitis may be related to edema.     

Effects of tidal volume and respiratory frequency on lung lymph flow.

Ventilation (V) increases lung lymph flow (Ql), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min(-1), results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min(-1) and compared with f = 10 min(-1). Three additional groups of six sheep were perfused for 100 min with control V (10 ml/kg, 10 min(-1)). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Ql and vice versa, without corresponding effects on the rate of edema formation. For the same change in V, changing Vt had a greater effect on Ql than changing f. The change in Ql caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Ql caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V altered Ql through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V-induced changes in fluid filtration.