Partitioning airway and lung tissue resistances in humans: effects of bronchoconstriction

1997 ◽  
Vol 82 (5) ◽  
pp. 1531-1541 ◽  
Author(s):  
David W. Kaczka ◽  
Edward P. Ingenito ◽  
Bela Suki ◽  
Kenneth R. Lutchen
Keyword(s):  
Frequency Dependence ◽  
Lung Tissue ◽  
Airway Resistance ◽  
Broad Band ◽  
Airway Wall ◽  
Lung Elastance ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
High Doses ◽  
Total Lung Resistance

Kaczka, David W., Edward P. Ingenito, Bela Suki, and Kenneth R. Lutchen. Partitioning airway and lung tissue resistances in humans: effects of bronchoconstriction. J. Appl. Physiol. 82(5): 1531–1541, 1997.—The contribution of airway resistance (Raw) and tissue resistance (Rti) to total lung resistance (R l ) during breathing in humans is poorly understood. We have recently developed a method for separating Raw and Rti from measurements of Rland lung elastance (El) alone. In nine healthy, awake subjects, we applied a broad-band optimal ventilator waveform (OVW) with energy between 0.156 and 8.1 Hz that simultaneously provides tidal ventilation. In four of the subjects, data were acquired before and during a methacholine (MCh)-bronchoconstricted challenge. The Rland Eldata were first analyzed by using a model with a homogeneous airway compartment leading to a viscoelastic tissue compartment consisting of tissue damping and elastance parameters. Our OVW-based estimates of Raw correlated well with estimates obtained by using standard plethysmography and were responsive to MCh-induced bronchoconstriction. Our data suggest that Rti comprises ∼40% of total Rlat typical breathing frequencies, which corresponds to ∼60% of intrathoracic Rl. During mild MCh-induced bronchoconstriction, Raw accounts for most of the increase in Rl. At high doses of MCh, there was a substantial increase in Rlat all frequencies and in El at higher frequencies. Our analysis showed that both Raw and Rti increase, but most of the increase is due to Raw. The data also suggest that widespread peripheral constriction causes airway wall shunting to produce additional frequency dependence in El.

Neurochemical control of tissue resistance in piglets

1995 ◽  
Vol 79 (3) ◽  
pp. 812-817 ◽  
Author(s):  
R. J. Martin ◽  
I. A. Dreshaj ◽  
M. J. Miller ◽  
M. A. Haxhiu
Keyword(s):  
Gas Exchange ◽  
Early Development ◽  
Lung Tissue ◽  
Respiratory System ◽  
Airway Resistance ◽  
Postnatal Life ◽  
Neural Function ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
First Time

Lung resistance may be influenced by chemoreceptor activity and modulated by inspiratory neural output; however, it is unknown whether the contractile elements of lung tissue participate in these changes during early development. In anesthetized paralyzed open-chest piglets, we measured phrenic electroneurogram, lung resistance (RL), and tissue resistance utilizing alveolar capsules to partition the hypercapnic and hypoxic responses of RL into tissue (Rti) and airway resistance (Raw) components. Inhalation of 7% CO2 significantly increased RL (7.4 +/- 0.5 to 11.3 +/- 0.6 cmH2O.l-1.s), Rti (5.2 +/- 0.5 to 6.9 +/- 0.5 cmH2O.l-1.s), and Raw (2.2 +/- 0.2 to 4.4 +/- 0.4 cmH2O.l-1.s). Inhalation of 12% O2 caused more modest increases in RL, Rti, and Raw. Oscillations in tracheal and alveolar pressures appeared in synchrony with phrenic activity in response to both chemoreceptor stimuli. Cholinergic blockade eliminated these oscillations and significantly reduced the hypercapnic and hypoxic responses of RL, Rti, and Raw. These data demonstrate for the first time that hypercapnia and hypoxia elicit a cholinergically mediated increase in Rti which, just like the airway component of RL, is modulated by inspiratory neural output and is present during early development. Such coordination in neural function throughout the respiratory system may serve to optimize gas exchange during early postnatal life.

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs

1992 ◽  
Vol 73 (5) ◽  
pp. 1908-1913 ◽  
Author(s):  
F. M. Robatto ◽  
S. Simard ◽  
H. Orana ◽  
P. T. Macklem ◽  
M. S. Ludwig
Keyword(s):  
Pressure Drop ◽  
Tidal Volume ◽  
Lung Volume ◽  
Airway Resistance ◽  
Positive End Expiratory Pressure ◽  
Alveolar Pressure ◽  
Lung Elastance ◽  
Tissue Resistance ◽  
Airway Caliber ◽  
Lung Resistance

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.

Effects of lung volume, volume history, and methacholine on lung tissue viscance

1989 ◽  
Vol 66 (2) ◽  
pp. 977-982 ◽  
Author(s):  
S. T. Kariya ◽  
L. M. Thompson ◽  
E. P. Ingenito ◽  
R. H. Ingram
Keyword(s):  
Lung Tissue ◽  
Volume Change ◽  
Lung Volume ◽  
Airway Resistance ◽  
Base Line ◽  
Lung Volumes ◽  
Lung Resistance ◽  
Before And After ◽  
The Subject ◽  
Volume History

We examined the effects of lung volume change and volume history on lung resistance (RL) and its components before and during induced constriction. Eleven subjects, including three current and four former asthmatics, were studied. RL, airway resistance (Raw), and, by subtraction, tissue viscance (Vtis) were measured at different lung volumes before and after a deep inhalation and were repeated after methacholine (MCh) aerosols up to maximal levels of constriction. Vtis, which average 9% of RL at base line, was unchanged by MCh and was not changed after deep inhalation but increased directly with lung volume. MCh aerosols induced constriction by increasing Raw, which was reversed by deep inhalation in inverse proportion to responsiveness. such that the more responsive subjects reversed less after a deep breath. Responsiveness correlated directly with the degree of maximal constriction, as more responsive subjects constricted to a greater degree. These results indicate that in humans Vtis comprises a small fraction of overall RL, which is clearly volume-dependent but unchanged by MCh-induced constriction and unrelated to the degree of responsiveness of the subject.

Total respiratory input and transfer impedances in humans

1985 ◽  
Vol 59 (2) ◽  
pp. 492-501 ◽  
Author(s):  
R. Peslin ◽  
C. Duvivier ◽  
C. Gallina
Keyword(s):  
Resonant Frequency ◽  
Frequency Dependence ◽  
Imaginary Part ◽  
Airway Resistance ◽  
The Real ◽  
Tissue Resistance ◽  
Gas Compressibility ◽  
Healthy Males

Total respiratory input (Zrs,in) and transfer (Zrs,tr) impedances were obtained from 4 to 30 Hz in 10 healthy males by simultaneously measuring mouth and chest flow while applying pseudo-random pressure variations at the mouth. Compared with Zrs,in, the real part of Zrs,tr was larger up to 10 Hz but exhibited a much stronger negative frequency dependence. The imaginary part was larger at all frequencies, with a resonant frequency (fn) at 6.0 +/- 0.8 Hz compared with 8.2 +/- 2.9 Hz for Zrs,in. The two impedances were analyzed with a model featuring airway resistance and inertance, alveolar gas compressibility, and tissue resistance, inertance, and compliance. A good fit was generally obtained but, in most cases, with a different partitioning of resistance between airway and tissue for Zrs,in and Zrs,tr. The data were also used to compute separately airway and tissue (Zt) impedances. In most subjects Zt could not be properly fitted with a simple resistance-inertance-compliance unit and was consistent with a slow (fn = 7.4 +/- 2.3 Hz) overdamped compartment in parallel with a fast (fn = 37.1 +/- 5.6 Hz) underdamped one.

Responses of lung parenchyma and airways to tachykinin peptides in piglets

1994 ◽  
Vol 77 (1) ◽  
pp. 147-151 ◽  
Author(s):  
I. A. Dreshaj ◽  
R. J. Martin ◽  
M. J. Miller ◽  
M. A. Haxhiu
Keyword(s):  
Lung Parenchyma ◽  
Neutral Endopeptidase ◽  
Smooth Muscle Contraction ◽  
Lung Compliance ◽  
Neurokinin A ◽  
Tidal Breathing ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
Dynamic Lung Compliance ◽  
Total Lung Resistance

The tachykinin peptides substance P (SP) and neurokinin A (NKA) have been shown to induce tracheal smooth muscle contraction in piglets, and the enzyme neutral endopeptidase has been shown to modulate this effect. In these studies, we compared the SP and NKA responsiveness of piglet airways and lung parenchymal tissues in anesthetized paralyzed open-chest piglets 2–3 wk old, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue resistance (Rti). During tidal breathing, pressure was measured at the trachea and in two alveolar regions by means of alveolar capsules. Intravenous administration of SP caused concentration-dependent increases in Rti and Raw and a decrease in dynamic lung compliance. Under baseline conditions, Rti contributed 74.6 +/- 1.9% (SE) of RL, and at any level of constriction, Rti accounted for > 50% of RL. The responses of Rti and Raw to NKA were negligible and were always significantly weaker than those to SP. These results indicate that both central airways and tissue contractile elements respond vigorously to SP, but not to NKA, in maturing piglets.

Differential effects of ozone on airway and tissue mechanics in obese mice

2004 ◽  
Vol 96 (6) ◽  
pp. 2200-2206 ◽  
Author(s):  
Y. M. Rivera-Sanchez ◽  
R. A. Johnston ◽  
I. N. Schwartzman ◽  
J. Valone ◽  
E. S. Silverman ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Tissue Mechanics ◽  
Lung Mechanics ◽  
Forced Oscillation Technique ◽  
Obese Mice ◽  
Wild Type ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
Baseline Values ◽  
Induced Changes

Obesity is an important risk factor for asthma. We recently reported increased ozone (O3)-induced hyperresponsiveness to methacholine in obese mice (Shore SA, Rivera-Sanchez YM, Schwartzman IN, and Johnston RA. J Appl Physiol 95: 938–945, 2003). The purpose of this study was to determine whether this increased hyperresponsiveness is the result of changes in the airways, the lung tissue, or both. To that end, we examined the effect of O3 (2 parts/million for 3 h) on methacholine-induced changes in lung mechanics with the use of a forced oscillation technique in wild-type C57BL/6J mice and mice obese because of a genetic deficiency in leptin ( ob/ob mice). In ob/ob mice, O3 increased baseline values for all parameters measured in the study: airway resistance (Raw), lung tissue resistance (Rtis), lung tissue damping (G) and elastance (H), and lung hysteresivity (η). In contrast, no effect of O3 on baseline mechanics was observed in wild-type mice. O3 exposure significantly increased Raw, Rtis, lung resistance (Rl), G, H, and η responses to methacholine in both groups of mice. For G, Rtis, and Rl there was a significant effect of obesity on the response to O3. Our results demonstrate that both airways and lung tissue contribute to the hyperresponsiveness that occurs after O3 exposure in wild-type mice. Our results also demonstrate that changes in the lung tissue rather than the airways account for the amplification of O3-induced hyperresponsiveness observed in obese mice.

Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance

1997 ◽  
Vol 83 (4) ◽  
pp. 1192-1201 ◽  
Author(s):  
Kenneth R. Lutchen ◽  
Heather Gillis
Keyword(s):  
Frequency Dependence ◽  
Lung Model ◽  
Airway Wall ◽  
Frequency Range ◽  
Airway Constriction ◽  
Lung Resistance ◽  
Central Airway

Lutchen, Kenneth R., and Heather Gillis. Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance. J. Appl. Physiol.83(4): 1192–1201, 1997.—We present a dog lung model to predict the relation between inhomogeneous changes in airway morphometry and lung resistance (Rl) and elastance (El) for frequencies surrounding typical breathing rates. The Rl and El were sensitive in distinct ways to two forms of peripheral constriction. First, when there is a large and homogeneous constriction, the Rl increases uniformly over the frequency range. The El is rather unaffected below 1 Hz but then increases with frequencies up to 5 Hz. This increase is caused by central airway wall shunting. Second, the Rl and El are extremely sensitive to mild inhomogeneous constriction in which a few highly constricted or nearly closed airways occur randomly throughout the periphery. This results in extreme increases in the levels and frequency dependence of Rland El but predominantly at typical breathing rates (<1 Hz). Conversely, the Rl and El are insensitive to highly inhomogeneous airway constriction that does not produce any nearly closed airways. Similarly, alterations in the Rl and El due to central airway wall shunting are not likely until the preponderance of the periphery constricts substantially. The Rland El spectra are far more sensitive to these two forms of peripheral constriction than to constriction conditions known to occur in the central airways. On the basis of these simulations, we derived a set of qualitative criteria to infer airway constriction conditions from Rl and El spectra.

Airway and tissue behavior during induced constriction in rats: intravenous vs. aerosol administration

1994 ◽  
Vol 76 (2) ◽  
pp. 830-838 ◽  
Author(s):  
T. Nagase ◽  
A. Moretto ◽  
M. S. Ludwig
Keyword(s):  
Lung Tissue ◽  
Freeze Substitution ◽  
Tissue Response ◽  
Similar Degree ◽  
Alveolar Pressure ◽  
Mechanically Ventilated ◽  
Lung Elastance ◽  
Airway Constriction ◽  
Tissue Resistance ◽  
Mean Linear Intercept

The distribution of contractile agonist during intravenous (i.v.) or aerosol (AR) administration is likely to be different. We questioned whether the different pattern of distribution would result in different effects on lung tissue response. We measured tracheal and alveolar pressure in open-chest mechanically ventilated [frequency 1 Hz, tidal volume 8 ml/kg, positive end-expiratory pressure (PEEP) 3 cmH2O] rats under control conditions and after i.v. or AR administration of saline or methacholine (MCh; i.v., 50 micrograms.kg-1.min-1; AR, 256 mg/ml). We calculated lung elastance and resistances of lung, tissue, and airway by fitting the equation of motion to changes in tracheal and alveolar pressure. Lungs were then frozen in situ with liquid nitrogen (PEEP=3 cmH2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of airway lumen to ideally relaxed area. Tissue distortion was assessed by measuring mean linear intercept between alveolar walls (Lm), atelectasis index (ATI) derived by calculating ratio of tissue to air space, and SD of Lm and ATI. I.v. and AR MCh increased lung resistance to a similar degree. However, changes in tissue resistance and lung elastance after AR MCh were significantly greater than those after i.v. MCh, whereas the change in airway resistance was significantly less. After i.v. MCh, airway constriction was prominent and evenly distributed. After AR MCh, airway constriction was less prominent and decreased as airway size decreased. Tissue distortion, i.e., SD of Lm and ATI, was significantly greater after AR than i.v. MCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway inhomogeneities contribute to apparent lung tissue mechanics during constriction

1996 ◽  
Vol 80 (5) ◽  
pp. 1841-1849 ◽  
Author(s):  
K. R. Lutchen ◽  
Z. Hantos ◽  
F. Petak ◽  
A. Adamicza ◽  
B. Suki
Keyword(s):  
Lung Tissue ◽  
Direct Evidence ◽  
Tissue Mechanics ◽  
Tissue Properties ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
Before And After ◽  
Oscillation Frequencies ◽  
G Ratio ◽  
Tissue Elastance

Recent studies have suggested that part of the measured increase in lung tissue resistance after bronchoconstriction is an artifact due to increased airway inhomogeneities. To resolve this issue, we measured lung impedance (ZL) in seven open-chest rats with the lungs equilibrated on room air and then on a mixture of neon and oxygen (NeOx). The rats were placed in a body box with the tracheal tube leading through the box wall. A broadband flow signal was delivered to the box. The signal contained seven oscillation frequencies in the 0.234- to 12.07-Hz range, which were combined to produce tidal ventilation. The ZL was measured before and after bronchoconstriction caused by infusion of methacholine (MCh). Partitioning of airway and tissue properties was achieved by fitting ZL with a model including airway resistance (Raw), airway inertance, tissue damping (G), and tissue elastance (H). We hypothesized that if the inhomogeneities were not significant, the apparent tissue properties would be independent of the resident gas, whereas Raw would scale as the ratio of viscosities. Indeed, during control conditions, the NeOx-to-air ratios for G and H were both 1.03 +/- 0.04. Also, there was a small increase in lung elastance (EL) between 0.234 and 4 Hz that was similar on air and NeOx. During MCh infusion, Raw and G increased markedly (45-65%), but the increase in H was relatively small ( < 13%). The NeOx-to-air Raw and H ratios remained the same. However, the NeOx-to-air G ratio increased to 1.19 +/- 0.07 (P < 0.01) and the increase in EL with frequency was now marked and dependent on the resident gas. These results provide direct evidence that for a healthy rat lung airway inhomogeneities do not significantly influence the lung resistance or EL vs. frequency data. However, during MCh-induced constriction, a large portion of the increase in tissue resistance and the altered frequency dependence of EL are virtual and a consequence of the augmented airway inhomogeneities.

Airway resistance and tissue elastance from input or transfer impedance in bronchoconstricted monkeys

2001 ◽  
Vol 90 (2) ◽  
pp. 571-578 ◽  
Author(s):  
Kristin R. Black ◽  
Bela Suki ◽  
Jeffrey B. Madwed ◽  
Andrew C. Jackson
Keyword(s):  
Airway Resistance ◽  
Nonhuman Primates ◽  
Lung Parenchyma ◽  
Airway Wall ◽  
Tissue Properties ◽  
Cynomolgus Monkeys ◽  
Airway Constriction ◽  
Tissue Resistance ◽  
System Input ◽  
Tissue Elastance

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) predominately 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 cmH2O · l−1 · s−1, respectively), but significantly different post-AS (20.5 ± 4.5 cmH2O · l−1 · s−1and 18.5 ± 5.2 cmH2O · 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.

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