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1 Division of Clinical Sciences, Telethon Institute for Child Health Research, School of Child Health, University of Western Australia, West Perth, Western Australia 6875, Australia; and 2 Department of Medical Informatics and Engineering, University of Szeged, Szeged A-6720, Hungary
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We
measured respiratory input impedance (1-25 Hz) in mice and
obtained parameters for airway and tissue mechanics by model fitting.
Lung volume was varied by inflating to airway opening pressure (Pao)
between 0 and 20 cmH2O. The expected pattern of changes in respiratory mechanics with increasing lung volume was seen:
a progressive fall in airway resistance and increases in the
coefficients of tissue damping and elastance. A surprising pattern was
seen in hysteresivity (
), with a plateau at low lung volumes
(Pao < 10 cmH2O), a sharp fall occurring between 10 and 15 cmH2O, and approaching a second (lower) plateau
at higher lung volumes. Studies designed to elucidate the mechanism(s)
behind this behavior revealed that this was not due to chest wall
properties, differences in volume history at low lung volume, time
dependence of volume recruitment, or surface-acting forces. Our data
are consistent with the notion that at low lung volumes the mechanics of the tissue matrix determine , whereas at high lung volumes the
properties of individual fibers (collagen) become more important.
respiratory mechanics; hysteresivity
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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ANIMAL MODELS ARE FREQUENTLY used to study the mechanisms underlying human lung diseases. In recent years, mice have become the "species of choice," especially for studying inflammatory and immunologically based diseases, because of the availability of reagents and the advances in transgenic technologies. Studies in mice are valuable for proof of concept studies and have furthered knowledge about disease mechanisms.
To study lung diseases, one needs the ability to measure lung function
and to understand how lung function changes under conditions likely to
be encountered in lung diseases. Most studies in mice reported in the
literature to date have used relatively simplistic methods for
measuring lung function. These techniques include barometric
plethysmography in unrestrained, conscious mice, measurement of
"overflow pressure," and measurements of airway resistance (Raw)
and dynamic compliance in a body plethysmograph (3). None
of these techniques is capable of partitioning lung function into
components representing the airways and lung tissues separately, which
is a distinct failure when attempting to understand disease mechanisms.
Recent technical developments have seen sophisticated measurements of
lung function used in mice, in which input impedance of the respiratory
system (Zrs) is measured over a frequency range from 0.25 to 20 Hz
(13, 16). A model including an airway compartment comprising a frequency-independent Raw and airway inertance and a
constant-phase tissue compartment comprising coefficients of tissue
damping (G) and tissue elastance (H) can then be fitted to
Zrs, allowing the partitioning of lung function into components representing the mechanical properties of the airways and lung tissue. Strictly speaking, this description applies only to the open-chest or isolated lung conditions; in the closed-chest conditions, the estimate of Raw may contain some Newtonian component from the chest
wall. The tissue mechanical properties have also been represented as
hysteresivity ( = G/H), an expression of the
coupling of the elastic and energy dissipative properties of lung
tissue (5). The is a material property of the tissue
and was originally defined as the energy dissipated relative to the
elastic energy stored in the tissue during cycling (5)
(e.g., during the breathing cycle) and it has been used to characterize
tissue mechanics in intact animals, lung tissue and muscle strips, and
single cells (4, 10-12, 17, 20, 21). Within a
particular animal, has been shown to be relative constant, changing
little with changes in tidal volume or ventilation frequency (5,
17).
Diseases that produce chronic inflammatory changes in the lungs are likely to alter lung volume because of a variety of mechanisms, including patchy atelectasis causing ventilation inhomogeneities and reducing lung volume, narrowing of small airways causing gas trapping, or increases in respiratory rate resulting in dynamic hyperinflation. In a number of species, including humans, respiratory mechanical properties are known to change with lung volume. Studies of the volume dependence of airways and lung tissues separately have shown that Raw decreases with increasing lung volume, whereas lung tissues become stiffer and tissue damping increases (15, 18). Similar data are not available for mice but are needed to accurately interpret changes in lung function induced in chronic disease models.
The present study was conducted to determine the changes occurring in
lung function, partitioned into components representing the airway and
lung tissues, with changes in lung volume from functional residual
capacity to close to total lung capacity in mice. The expected changes
in Raw, G, and H with lung volume were demonstrated;
however, a marked decrease in with increasing lung volume was seen.
Studies were then undertaken to investigate the mechanisms responsible
for changes in with lung volume.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Animal Preparation
Female BALB/c mice, 8-10 wk old, were studied. Each mouse was anesthetized with 0.1 ml/10 g of a mixture containing xylazine (2 mg/ml; Bayer) and ketamine (40 mg/ml; Parnell Laboratories). Two-thirds of the dose was given to induce anesthesia, with the remainder given when the animal was attached to the ventilator. Additional doses were given approximately each 40-60 min, as required. Once surgical anesthesia had been established, a tracheostomy was performed and a polyethylene cannula (length = 1.0 cm, ID = 0.0813 cm) inserted. Mice were ventilated with a tidal volume of 8 ml/kg at a rate of 450 breaths/min, with a positive end-expiratory pressure (PEEP) of 2 cmH2O, by using a custom-designed ventilator (flexiVent, Scireq, Montreal, PQ, Canada). This rate is used to suppress the animal's drive to breathe, so muscle relaxation is not required for measurements made during pauses in ventilation. The animal handling and study protocol conformed to the guidelines of the Australian National Health and Medical Research Council and were approved by the Animal Ethics Committee of the Institute for Child Health Research.Measurement of Lung Function
Lung function was measured during brief pauses (time = 6 s) of ventilation, during which the animal was switched from the ventilation circuit to the measurement circuit (Fig. 1). A forcing function, with 25 equidistant frequency components between 1 and 25 Hz, was generated by the loudspeaker and delivered to the animal via a wave tube (length = 100 cm, ID = 0.116 cm). The power of the low-frequency components was enhanced to match the frequency dependence of the impedance magnitude. The component phase angles of the forcing function were selected so that the peak-to-peak amplitude of the composite signal was minimal at the given component amplitudes (2 cmH2O).
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Volume Dependence of Respiratory Mechanics
To determine the volume dependence of respiratory mechanics, measurements were made in 8 BALB/c mice [group mean weight 25.4 ± 6.4 (SD) g] at transrespiratory pressures of 0, 2, 5, 10, 12.5, 15, and 20 cmH2O. The measurement circuit was set to the desired pressure before the animal was switched into the circuit. Approximately 3 s were allowed for the animal to equilibrate with the measurement circuit before the forcing function was introduced. In preliminary studies, the order in which pressures were applied was investigated and found not to influence the results (data not shown). In all studies reported here, the pressures were applied systematically from lowest to highest. At each pressure, four discrete data epochs were collected, separated by at least 30 s of normal ventilation, with a PEEP of 2 cmH2O, and this ventilation set the premeasurement volume history. Individual spectra were averaged and the constant-phase model (7) fitted as follows
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(1) |
is the
angular frequency, and 
is a function of G and H only and
therefore is not an independent model parameter. The model
fitting was accomplished by miminizing the squared sum of relative
distances between measured and modeled data. The impedance of the
tracheal cannula was estimated separately, and the cannula resistance
and inertance were removed from R and I, respectively. The values of I
were small after correction and are not reported
Determination of the Mechanism of Changes in With Lung Volume
Influence of the chest wall.
To determine the influence of the chest wall on the volume dependence
of respiratory mechanics, particularly of , five mice were studied
with the chest wall intact and after midline sternotomy and wide
retraction of the rib cage. Lung function was measured by using a
protocol identical to that described above, with the exception that
data were not collected at a transpulmonary pressure of 0 cmH2O. We also measured volume dependence, by using a
protocol identical to that used in the open-chest conditions, in three sets of isolated lungs that were suspended by the tracheal cannula and unsupported.
Volume history at low lung volumes.
To determine whether the volume history preceding the measurement was
responsible for the pattern of change in with lung volume, i.e.,
higher values in at low lung volumes, the closed-chest protocol was
repeated in a group of mice (n = 4) ventilated with a
PEEP of 5 cmH2O instead of 2 cmH2O between each
measurement of Zrs.
Time dependence of volume recruitment. To test the possibility that volume recruitment at any given pressure may be a time-dependent phenomenon, two protocols were undertaken (n = 4 animals). 1) The time allowed for equilibration between the mouse and the measurement circuit was doubled to 6 s. Lung function was measured by using a protocol identical to that described above. 2) Measurements were made at transrespiratory pressures of 5, 20, and 5 cmH2O without measurements at other pressures intervening and at 10, 20, and 10 cmH2O without measurements at other pressures intervening (abbreviated protocol).
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Volume Dependence of Respiratory Mechanics
The impedance data were consistent with the model at all transrespiratory pressures. Figure 2 displays a representative pair of Zrs spectra obtained at the lowest and highest transpulmonary pressures obtained in one mouse. Mean fitting errors were <3% at all pressures and did not show any systematic pattern with increasing transrespiratory pressure. Group mean fitting errors (± SD) were 2.18 ± 0.16, 2.88 ± 0.34, 2.28 ± 0.26, 2.83 ± 0.19, 2.46 ± 0.42, 2.06 ± 0.47, and 2.08 ± 0.21% at transrespiratory pressures of 0, 2, 5, 10, 12.5, 15, and 20 cmH2O, respectively.
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The volume dependence of mechanical parameters of the total respiratory
system is shown in Fig. 3 (solid
symbols). As measurements were made at progressively higher
transrespiratory pressures, R decreased progressively from 421 ± 20 (SE)
cmH2O · l
1 · s
at a transrespiratory pressure of 0 cmH2O to 176 ± 14 cmH2O · l1 · s
at 20 cmH2O (Fig. 3A). The patterns of volume
dependence of G and H were somewhat more complex, decreasing
from 0.72 ± 0.032 × 104 and 3.06 ± 0.18 × 104 cmH2O/l, respectively, at a
transrespiratory pressure of 0 cmH2O, to minimum values of
0.60 ± 0.026 × 104 and 2.21 ± 0.12 × 104 cmH2O/l, respectively, at a
transrespiratory pressure of 5 cmH2O before increasing to
maximum values of 1.28 ± 0.46 × 104 and
9.77 ± 0.53 × 104 cmH2O/l,
respectively, at a transrespiratory pressure of 20 cmH2O (Fig. 3, B and C).
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The pattern of volume dependence of was most surprising, with
values increasing from 0.24 ± 0.05 at a transrespiratory pressure of 0 cmH2O to a plateau value of ~0.27 between pressures
of 2 and 10 cmH2O before decreasing abruptly between
pressures of 10 and 15 cmH2O to approach a lower value of
~0.13 at a transrespiratory pressure of 20 cmH2O (Fig.
3D).
Influence of the Chest Wall on Respiratory Mechanics
The influence of the chest wall on respiratory mechanics in mice is shown by comparing the open-chest with the closed-chest parameter values in Fig. 3. The chest wall contributes ~6% to R with little change over the range on lung volumes studied (Fig. 3A). The contributions of the chest wall to tissue mechanics are also shown in Fig. 3. There is a moderate contribution to G (average 20%; Fig. 3B) but no contribution to H (average 0.7%; Fig. 3C). The chest wall does contribute to the value of measured in the intact animal (average 20%) (Fig. 3D).
However, as can be clearly seen in Fig. 3, the volume-dependent
behavior of respiratory mechanics is not due to the contribution of the
chest wall. Specifically, the pattern of change in with increasing
lung volume is identical in the open-chest measurements to those with
the chest wall intact. In addition, the pattern of change in in the
isolated lungs was similar to that seen in both the open- and
closed-chest conditions, confirming that this pattern could not be
attributed to the influence of the chest wall (Fig.
4).
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Influence of Volume History on the Volume-dependent Behavior of Respiratory Mechanics
Altering the premeasurement volume history by setting PEEP at either 2 or 5 cmH2O had no influence on either the values of R, G, H, and measured at any lung volume or in the
pattern of change in these variables with increasing lung volume.
Figure 5 shows the patterns of change in
with increasing transrespiratory pressure measured with both
protocols.
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Influence of Time-dependent Recruitment of Lung Volume on the Volume-dependent Behavior of Respiratory Mechanics
Neither protocol used to address any potential effect of time-dependent recruitment of lung volume on the patterns of volume dependence behavior of respiratory parameters disclosed any difference in these patterns. The change in equilibration time from 3 to 6 s did not result in a change in any of the mechanical parameters, including, at any pressure (data not shown). Similarly, there was
no change in any parameter when the abbreviated protocol was used (data
not shown).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The results of the present study show that respiratory mechanics,
measured by using forced oscillations, exhibit the expected decrease in
R with increasing lung volume together with the expected increase in G
and H. These results confirm the changes that will occur in
respiratory mechanics under circumstances in which lung volumes change,
such as will be encountered in models of chronic lung disease. The
changes seen in were unexpected.
The mechanical properties of the lung parenchyma are determined partly
by a tension skeleton made up of connective tissue fibers that spread
throughout the lung in an organized fashion and partly by
surface-acting forces (21). The tension skeleton consists
of 1) axial fibers that fan out centrifugally from the hilum
along the branching airway tree, 2) peripheral fibers that originate in the pleura and penetrate centripetally into the lung, and
3) alveolar septal fibers that join the two
(21). The pulmonary interstitium contains myofibroblasts
that contain actin and myosin microfilaments of the smooth muscle type,
collagen and elastin fibers, and some free extracellular fluid related
to lymph. From a mechanical point of view, the collagen and elastin
fibers are intimately associated and cannot really be considered to be
separate (21). Fredberg and Stamenovic (5)
proposed the structural damping paradigm, according to which the
dissipative properties of lung tissue (tissue damping or
frequency-dependent tissue resistance) and the elastic properties were
coupled and could be expressed as . Under this paradigm, should
only depend on the material composition of the tissue. Indeed, has
been shown to be relatively constant across species and under a variety
of experimental circumstances, although has been shown to increase
in response to constrictor agonists both in vivo and in vitro (8,
12, 14) and to differ in magnitude between intact lungs and
tissue strips (17). Sakai et al. (17)
measured in intact rats, after partial thoracotomy, achieved by
opening the diaphragm to induce bilateral pneumothoraxes, in isolated
lungs, and in tissue strips. They compared the values of measured
under these conditions at several lung volumes with estimated
directly from tissue strip preparations. They reported higher values of
in the intact lungs (closed chest > open chest) and that in the isolated lungs was similar to that in the tissue strips and
concluded that was primarily determined by lung connective tissue
and that the higher values seen in lungs measured in situ were a
consequence of "compartment-like heterogeneity." This conclusion is
consistent with the original hypothesis of Fredberg and Stamenovic (5).
The volume-dependent behavior of reported in the present study
warrants further examination. We found that was relatively constant
at low lung volumes (between transrespiratory pressures of 2 and
10 cmH2O). These data are consistent with the
majority of reports in the literature in different species, with little change reported in within the experimental conditions examined. The
abrupt fall in seen as lung volume increased (between
transrespiratory pressures of 10 and 15 cmH2O) was
unexpected and seemingly at odds with the concepts of expressed in
the literature. However, we are not aware of any data in the literature
that systematically examine the volume-dependent behavior of over
an extended volume range. In an attempt to understand the mechanism
underlying this phenomenon, we undertook a series of studies to examine
possible contributory factors.
We examined the influence of the chest wall on respiratory mechanics and on the volume-dependent behavior by measuring respiratory mechanics before and after midline sternotomy and widely retracting the rib cage. As shown in Fig. 3, the chest wall did contribute to respiratory mechanics, as measured with low-amplitude forced oscillations. The average contribution of the chest wall to R was 6%, and the average contribution to G was 20%. These contributions are of similar proportions to studies that used similar techniques in other species, including rats (14) and human infants (Z. Hantos and P. Sly, unpublished observations). Perhaps surprisingly, our results suggest that the elastic properties of the chest wall do not contribute to the elastic behavior of the respiratory system. This finding is at odds with studies in other species (as above) and is counterintuitive. The most likely explanation for this finding is the likely difference in the pattern of lung expansion in the closed and opened conditions. In a supine, mechanically ventilated mouse with the chest wall intact, the most obvious expansion during inspiration is seen in the abdominal compartment. This implies that the lung expands by pushing the diaphragm down, moving the abdominal wall outward. When the chest wall is opened by midline sternotomy and cutting the diaphragm bilaterally, as in the present study, the lungs, which are no longer restrained by the rib cage, can be seen to expand outward rather than toward the abdominal cavity. Thus the motion and expansion of the lungs may well be very different under the two conditions and lead one to question the validity of measurement of respiratory mechanics made with the chest wall opened. The values we obtained for R, G, and H at 2 cmH2O with the chest wall opened (Fig. 3) were similar to those reported by Tomioka et al. (19).
Despite the concerns expressed above about the validity of the
open-chest measurements, as can be seen in Fig. 3D, the
influence of the chest wall cannot explain the volume-dependent
behavior of . Although the magnitude of fell after opening of
the chest wall, the pattern of volume dependence was identical. In
addition, we measured the volume dependence in a group of excised lungs and found essentially the same pattern of volume dependence as seen in
both the closed- and open-chest conditions, confirming that this
phenomenon is not due to the influence of the chest wall. However, the
rise seen in between 0 and 5 cmH2O in the closed-chest
conditions was not seen with the chest wall widely open in the isolated
lungs (between 2 and 5 cmH2O), and this may be a property
of the chest wall.
We then examined the possibility that our study protocol allowed
ventilation inhomogeneity and patchy atelectasis to develop between
measurements that was not completely overcome at low lung volumes but
was at high lung volumes, leading to an artifactual volume-dependent
behavior. Ventilation inhomogeneity with partial closure of some
peripheral airways would be expected to result in an increase in G that
is not matched by a similar increase in H and an increase in
. Studies in rats undergoing methacholine challenge showed such a
pattern (14) and confirmed that peripheral inhomogeneity
was indeed responsible by ventilating the animals with a gas mixture of
20% oxygen and 80% neon and showing gas-dependent changes in G. We
approached this possibility in several ways. We first considered that
the volume history set by a PEEP of 2 cmH2O might not have
been sufficient to prevent atelectasis and/or ventilation inhomogeneity
from developing in our anesthetized, supine animals. In a separate
group of animals, we repeated our measurement protocol with a volume
history set by a PEEP of 5 cmH2O, a pressure likely to be
well above the elastic equilibrium pressure of the respiratory system
in mice. The data recorded with a PEEP of 5 cmH2O and of 2 cmH2O in the same animals were identical (Fig. 5) and did
not support the notion that the premeasurement volume history was
responsible for the volume-dependent behavior in respiratory mechanics,
especially in . Next we used two separate protocols to examine the
possibility that more time than we were allowing was required to
"open" the lungs at low lung volumes, whereas sufficient time was
available to higher lung volumes (1). In a separate group
of animals, we allowed either 3 or 6 s for the animal to
equilibrate with the preset measurement after switching the animal into
the measurement circuit before measuring respiratory mechanics. Again
the measurements made in individual animals were identical with either
protocol, suggesting that time-dependent recruitment of lung volume was
not responsible for the pattern of volume-dependent behavior we
observed. Additionally, we altered the measurement protocol, measuring
respiratory mechanics at a transrespiratory pressure of 5 cmH2O immediately before and after measurements made at 20 cmH2O and at 10 cmH2O immediately before and
after measurements made at 20 cmH2O. Again, these
measurements were identical in individual animals, strongly suggesting
that the results we are reporting are a function of the
transrespiratory pressure at which the measurements were made rather
than a function of the measurement protocol.
When measurements of respiratory mechanics are made in vivo, the
surface-acting forces are also likely to contribute to the parenchymal
mechanics. As lung volume decreases, the radius of curvature of alveoli
increases, resulting in an increased surface tension and tendency for
the alveoli to collapse. Surfactant reduces surface tension and
minimizes the tendency for alveoli to collapse. As lung volume
decreases the surfactant monolayer is compressed and "folds" in the
alveoli. Surfactant protein C (SP-C) is thought to be involved in this
process, and mice deficient in SP-C show alveolar instability at low
lung volumes (6). As part of another study
(9), we had the opportunity of examining the
volume-dependent behavior of in transgenic mice with differing
combinations of deficiencies of surfactant protein B (SP-B) and/or
SP-C, with differing surfactant functions and differing abilities to
lower surface tension, especially at low lung volumes. Measurements of
respiratory mechanics were made with a different measurement system,
the flexiVent, with an oscillatory signal with similar frequency
content but larger amplitude that that used in the present study. As
shown in Fig. 6, an identical pattern of
volume-dependent behavior was seen in in these mice as was seen in
the present study. These data show that surface-acting forces are
unlikely to contribute to the volume-dependent behavior of , with
higher values at low lung volume as seen in the present study. Also, the larger amplitude signal used in the surfactant study, together with
the different system used to measure oscillatory mechanics, strongly
suggests that the results of the present study are not peculiar to the
measurement conditions used but reflect an inherent property of
mice. In addition, different strains of mice were used in the
two studies [BALB/c in the present study and National Institutes of
Health Swiss Black (SP-C) and FVB (SP-B) in the surfactant study],
suggesting that this phenomenon is not a function of a single strain of
mouse. Indeed, we have seen similar volume-dependent changes in
in both rats and rabbits (P. D. Sly, R. A. Collins, C. Thamrin, D. J. Turner, Z. Hantos, and J. Kovar, unpublished observations).
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Mijailovich et al. (11) examined the relative
contributions of tissue matrix (represented by rabbit lung tissue
strips) and of individual fibrous components (represented by pigeon
ligamentum propatagiale) to test a prediction that " of the tissue
matrix must be greater, and typically much greater, than that of its isolated fibrous constituents." They found that of the lung parenchyma decreased moderately with increasing frequency and was
approximately an order of magnitude greater than that of the ligamentum
propatagiale. These findings can be used to shed some light on
the mechanism of the volume dependence of , reported in the
present study. At low lung volumes, i.e., at the volumes close to the
normal breathing volume of the mice, the mechanical behavior of the
lung tissues would be expected to be dominated by that of the tissue
matrix. As lung volume increases to volumes that would not
frequently be reached during normal breathing, the tissue matrix is
stretched. Our data are consistent with the notion that at high lung
volumes a transition occurs and that the mechanical behavior of the
lung tissues becomes dominated by that of individual fibers, most
likely collagen fibers. This is in accordance with the findings that
is smaller in elastance-treated parenchymal strips than in those
after collagenase pretreatment (20).
Finally, data from another study investigating the mechanisms of
bleomycin-induced lung fibrosis (2) provide support for the interpretation of the mechanisms involved in the volume-dependent behavior of discussed above. Mice in which lung fibrosis was induced show a different pattern of volume dependence of compared with controls (Fig. 7). Although both
groups show a fall in from a similar plateau at low lung volumes (0 and 2 cmH2O) and approach a new (lower) plateau (similar
between groups) at high volume (20 cmH2O), the mice with
lung fibrosis begin this transition at a lower lung volume. The mice
with fibrosis have a significantly lower at 10 cmH2O
(2-way repeated-measures ANOVA, post hoc Tukey's test,
P < 0.05) than controls. These data suggest that as
the amount of collagen in the lung connective tissue network increases, the transition from mechanical behavior dominated by the tissue matrix
to that dominated by the behavior of single (collagen) fibers occurs at
a lower lung volume. If lung fibrosis shifts the volume at which the
value of makes the transition from the level seen at low lung
volume to that seen at high lung volume, it may provide a noninvasive
assessment of the structural changes in the lung parenchyma. This
possibility requires further specific investigation and is beyond the
scope of the present study.
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In conclusion, we have measured the volume-dependent behavior of
respiratory mechanics in the mouse and demonstrated an unexpected pattern in . The falls from an initial plateau value of ~0.27 at low lung volumes to a second, lower, plateau value of ~0.13 at
lung volumes approaching total lung capacity. Mice with normal lungs
make this transition between lung volumes associated with transrespiratory pressures of 10-15 cmH2O. Our data
strongly suggest that this pattern is not due to the influence of the
chest wall, regional inhomogeneity at low lung volumes, time dependence
of lung volume recruitment, or surface tension-lowering ability at low
lung volumes. Preliminary data do suggest that this pattern may be a
fundamental property of the connective tissue fibers of the pulmonary
parenchyma and that increasing the amount of collagen by inducing
pulmonary fibrosis alters this pattern. Further studies are required to
determine whether the measurement of the volume dependence of may
hold promise as a noninvasive method for assessing the structural
integrity of the lungs.
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ACKNOWLEDGEMENTS |
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This work was supported by National Health and Medical Research Council of Australia Grants 211912 and 10199 and by Hungarian Scientific Research Fund Grant OTKA T30670. P. D. Sly is a Senior Principal Research Fellow of the National Health and Medical Research Council of Australia.
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FOOTNOTES |
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Address for reprint requests and other correspondence: P. D. Sly, Telethon Institute for Child Health Research, PO Box 855, West Perth, Western Austrailia 6875, Australia (E-mail: peters{at}ichr.uwa.edu.au).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published August 30, 2002;10.1152/japplphysiol.00596.2002
Received 3 July 2002; accepted in final form 28 August 2002.
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REFERENCES |
|---|
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Brown, RH,
and
Mitzner W.
Delayed distension of constricted airways with lung inflation in vivo.
Am J Respir Crit Care Med
162:
2113-2116,
2000
2.
Collins, RA,
Turner DJ,
Dunsmore SE,
Chua F,
Roes J,
Laurent GJ,
and
Sly PD.
Initial characterization of lung function in mice deficient in neutrophil proteinases (Abstract).
Am J Respir Crit Care Med
165:
A802,
2002.
3.
Drazen, JM,
Finn PW,
and
De Sanctis GT.
Mouse models of airway responsiveness: physiological basis of observed outcomes and analysis of selected examples using these outcome indicators.
Annu Rev Physiol
61:
593-625,
1999[ISI][Medline].
4.
Fabry, B,
Maksym GN,
Butler JP,
Glogauer M,
Navajas D,
and
Fredberg JJ.
Scaling the microrheology of living cells.
Phys Rev Lett
87:
1-4,
2001.
5.
Fredberg, JJ,
and
Stamenovic D.
On the imperfect elasticity of lung tissue.
J Appl Physiol
67:
2408-2419,
1989
6.
Glasser, SW,
Burhans MS,
Korfhagen TR,
Na CL,
Sly PD,
Ross GF,
Ikegami M,
and
Whitsett JA.
Altered stability of pulmonary surfactant in SP-C deficient mice.
Proc Natl Acad Sci USA
98:
6366-6371,
2001
7.
Hantos, Z,
Daroczy B,
Suki B,
Nagy S,
and
Fredberg JJ.
Input impedance and peripheral inhomogeneity of dog lungs.
J Appl Physiol
72:
168-178,
1992
8.
Hantos, Z,
Petak F,
Adamicza A,
Daroczy B,
and
Fredberg JJ.
Differential responses of global airway, terminal airway, and tissue impedances to histamine.
J Appl Physiol
79:
1440-1448,
1995
9.
Ikegami, M,
Weaver TE,
Conkright JJ,
Sly PD,
Ross GF,
Whitsett JA,
and
Glasser SW.
Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury.
J Appl Physiol
92:
519-526,
2002
10.
Ludwig, MS,
and
Dallaire MJ.
Structural composition of lung parenchymal strips and mechanical behavior during sinusoidal oscillation.
J Appl Physiol
77:
2031-2035,
1994.
11.
Mijailovich, SM,
Stamenovic D,
Brown R,
Leith DE,
and
Fredberg JJ.
Dynamic moduli of rabbit lung tissue and pigeon ligamentum propatagiale undergoing uniaxial loading.
J Appl Physiol
76:
773-782,
1994
12.
Nagase, T,
and
Ludwig MS.
Antigen-induced responses in lung parenchymal strips during sinusoidal oscillation.
Can J Physiol Pharmacol
76:
176-181,
1998[ISI][Medline].
13.
Petak, F,
Habre W,
Donate YR,
Hantos Z,
and
Barazzone-Argiroffo C.
Hyperoxia-induced changes in mouse lung mechanics: forced oscillations vs. barometric plethysmography.
J Appl Physiol
90:
2221-2230,
2001
14.
Petak, F,
Hantos Z,
Adamicza A,
and
Sly PD.
Methacholine-induced bronchoconstriction in rats: effects of intravenous vs. aerosol delivery.
J Appl Physiol
82:
1479-1487,
1997
15.
Petak, F,
Hayden MJ,
Hantos Z,
and
Sly PD.
Volume dependence of respiratory impedance in infants.
Am J Respir Crit Care Med
156:
1172-1177,
1997
16.
Pillow, JJ,
Korfhagen TR,
Ikegami M,
and
Sly PD.
Overexpression of TGF- increases lung tissue hysteresivity in transgenic mice.
J Appl Physiol
91:
2730-2734,
2001
17.
Sakai, H,
Ingenito EP,
Mora R,
Abbay S,
Cavalcante FSA,
Lutchen KR,
and
Suki B.
Hysteresivity of the lung and tissue strip in the normal rat: effects of heterogeneities.
J Appl Physiol
91:
737-747,
2001
18.
Sly, PD,
Brown KA,
Bates JHT,
Macklem PT,
Milic-Emili J,
and
Martin JG.
Effect of lung volume on interrupter resistance in cats challenged with methacholine.
J Appl Physiol
64:
360-366,
1988
19.
Tomioka, S,
Bates JHT,
and
Irvin CG.
Airway and tissue mechanics in a murine model of asthma: alveolar capsule vs. forced oscillations.
J Appl Physiol
93:
263-270,
2002
20.
Yuan, H,
Ingenito EP,
and
Suki B.
Dynamic properties of lung parenchyma: mechanical contributions of fiber network and interstitial cells.
J Appl Physiol
83:
1240-1431,
1997.
21.
Yuan, H,
Kononov S,
Cavalcante FSA,
Lutchen KR,
Ingenito EP,
and
Suki B.
Effects of collagenage and elastase on the mechanical properties of lung tissue strips.
J Appl Physiol
89:
3-14,
2000
22.
Weibel, ER.
Functional morphology of lung parenchyma.
In: Handbook of Physiology. The Respiratory System. Mechanics of Breathing. Bethesda, MD: Am. Physiol. Soc, 1986, vol. III, p. 89-112, sect. 3, pt. 1, chapt. 8.
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and 20 cmH2O (
, 
), together
with the model fits (solid lines). Values are means ± SD. Data
corrupted by the heartbeat and its harmonics exhibited a great scatter
and were discarded from the model fitting (
