| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9034
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
In immature dogs after pneumonectomy (PNX), pulmonary viscous resistance is persistently elevated predominantly as a result of a high airway resistance (Raw). We examined the anatomical basis for this observation by using computerized tomography scans obtained from foxhounds 4-10 mo after right PNX. Airways of the left lower lobe were followed from generations z = 0 (trachea) to z = 12. By 4 mo post-PNX, airway length increased significantly relative to sham-operated dogs, but airway cross-sectional area (CSA) did not. By 10 mo post-PNX, average airway CSA was 24% above that in controls. Theoretically, the increased airway length and CSA should reduce lobar Raw by 50%. However, post-PNX airway dilatation did not normalize total CSA, and estimated resistance due to turbulence and convective acceleration increased threefold; i.e., the 50% reduction in lobar Raw would be offset by the loss of four of seven lobes. Thus the expected reduction in work of breathing in the whole animal is only ~30%, consistent with previously measured work of breathing in pneumonectomized dogs. We conclude that airway structure adapts slowly and incompletely, resulting in limited functional compensation.
airway resistance; cross-sectional area; airway length; lung resection; dog; computerized tomography
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
IN IMMATURE ANIMALS RAISED to maturity after pneumonectomy (PNX), vigorous compensatory growth of alveolar septal tissue and respiratory bronchioles (16, 26) completely normalizes lung volume, gas exchange, and maximal oxygen uptake. However, pulmonary viscous resistance and ventilatory power requirements measured at any given ventilation at rest and during exercise remain approximately 2-2.5 times those in normal dogs (27, 28). As tissue viscosity becomes negligible at respiratory frequencies greater than ~1.0 Hz, and dogs breathe at frequencies between 1 and 3 Hz when ventilation exceeds ~70 l/min, the increased viscous resistance during exercise is almost entirely due to an increased airway resistance (Raw) (2). These observations suggest limited adaptation of conducting airways, which primarily form in fetal life, compared with gas-exchange regions of the lung, which continue to grow after birth. Others have also reported that conducting airways do not participate equally with respect to the parenchyma during postnatal maturation (9, 11, 12) or adaptation to high altitude (4) or after PNX (10); this pattern has been termed "dysanaptic" (unequal) lung growth (9). There is little information concerning the structural basis, magnitude, or time course of airway adaptation after PNX. Airway dimensions in vivo have not been assessed. The interaction between compensatory airway remodeling and normal airway growth during somatic maturation is also unknown.
The purpose of the present study is to define the anatomical basis underlying the observation of a persistent increase in energy cost of breathing against a high Raw after PNX. Intuitively, airways can adapt by lengthening and/or dilatation. These changes exert opposing effects; airway lengthening is expected to increase Raw whereas dilatation is expected to decrease Raw. We hypothesized that the net effect will be a compensatory reduction in Raw but the adaptation will be slow and incomplete. We measured airway dimensions from spiral computerized tomographic (CT) scans at a constant transpulmonary pressure in foxhounds at two time points (4 and 10 mo) after right PNX at 2 mo of age. We determined the average length and cross-sectional area (CSA) of each generation (z) of airway from trachea (z = 0) to z = 12 and beyond in the left lower lobe. From the anatomical data, we estimated the lobar pressure gradient and work of breathing at a given flow rate to determine whether changes in Raw estimated from in vivo dimensions are in keeping with previously measured changes in Raw.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Animal procedures.
The protocol was approved by the Institutional Animal Care and Research
Advisory Committee. Eleven litter-matched foxhounds (2 mo of age)
underwent removal of the right lung (PNX, n = 5) or
right thoracotomy without lung resection (Sham, n = 6)
under isoflurane anesthesia; surgical techniques have been described elsewhere (26). At 6 mo of age (4 mo after surgery),
spiral CT scan was performed (GE High Speed CTI). After overnight
fasting, animals were sedated with subcutaneous injections of
acepromazine (0.15 mg/kg) and atropine (0.023 ml/kg) and anesthetized
with intravenous propofol (4-8 mg/kg for induction followed by 0.4 mg · kg
1 · min1 infusion).
After intubation with a cuffed endotracheal tube, animals were placed
in the supine position on the CT table and mechanically ventilated
(model 607, Harvard Apparatus, Millis, MA) at a tidal volume of 15 ml/kg of air and a respiratory rate sufficient to eliminate spontaneous
breathing effort. Before each imaging sequence, the lungs were
hyperinflated with three cumulative tidal breaths (to 45 ml/kg),
followed by passive expiration to functional residual capacity. The
endotracheal tube was then connected to a 3-liter calibrated syringe
that delivered a volume of air previously determined to inflate the
lungs to a transpulmonary pressure of 20 cmH2O (~45
ml/kg). After the lungs were inflated, the breath was held for
40-45 s while the scanning was performed, after which the animal
was switched back to the respirator. A scout film was first obtained,
followed by volumetric CT imaging from the lung apex to the
costophrenic angle using collimation of 3 × 3 mm; images were
reconstructed at 1-mm intervals, resulting in 260-310 images per
animal. During breath holding, O2 is consumed and
CO2 is produced; net volume loss is minimal. Airway
pressure was continuously monitored. Immediately after volume delivery, there was an exponential decline in pressure of ~3 cmH2O
due to stress relaxation not associated with volume change, followed by
a linear fall of ~2 cmH2O/min reflecting a 2-3%
decline in volume during the period of breath hold. Because dogs reach
somatic maturity at 9-12 mo of age, we repeated CT scan in three
animals of each group at 12 mo of age (10 mo after surgery) by using
the same protocol.
Analysis of CT images.
The CT images were analyzed by use of Adobe PhotoShop v.5 (Adobe
Systems, San Jose, CA) and Object-Image v.1.62 (a public-domain program
based on NIH Image by Norbert Vischer, University of Amsterdam, Amsterdam, Netherlands). Wire frame images of the airways were created
by using Rotater (a public-domain Macintosh program by Craig Kloenden,
University of Adelaide, Adelaide, Australia) for rotating
user-specified points and lines in three dimensions. The area occupied
by lung in each image was traced and multiplied by the slice thickness
(1 mm) to obtain volume; total lung volume was calculated from the sum
of the volume of all images. The CT density (in Houndsfeld units)
of tracheal air (
air) and muscle tissue
(muscle) was measured and used to partition the total lung volume (Vtotal) into air (Vair) and tissue
(Vtissue) volume, because the average CT density of the
lung (lung) is directly proportional to the ratio of
tissue and air
|
(1) |
|
(2) |
Estimating laminar flow resistance in left lower lobe.
To interpret the functional significance of airway dimensional changes,
we extrapolated airway length and diameter into lobar flow resistance
as described by Rohrer (19, 24). Airflow (
, in l/s)
through an airway is assumed to be proportional to the volume fraction
of the lung subserved by that airway. The left lung in Sham animals
constitutes ~42% of total lung volume and receives 42% of total
airflow (23); thus flow through the left main bronchus
(z = 1) is
|
(3) |
|
(4) |
|
(5) |
PLaminar, in cmH2O) across a given airway
within the left lower lobe is directly proportional to total flow and
inversely proportional to the expected number of airways in that
generation (NA)
|
(6) |
1) is
given by Poiseuille's Law as a function of airway length (L, in mm), diameter (dz, in mm),
viscosity of air (µ = 1.83 × 10-4
dyn · s · cm2), and gravitational
acceleration (g = 980 dyn/g)
|
(7) |
Estimating turbulent flow resistance in left lower lobe.
The critical flow velocity (c) above which the
Reynolds number exceeds 2,000 is calculated for each airway generation
|
(8) |
is the density of inspired gas. When flow through a
generation is below c, laminar flow predominates and
PLaminar of that generation is estimated as in
Eqs. 6-7. When flow exceeds c,
turbulent flow predominates; the pressure gradient due to turbulent
flow (PTurbulent) in that airway generation is given by
|
(9) |
Estimating lobar resistance due to convective acceleration.
In addition to laminar and turbulent flow resistances, a pressure
gradient also develops due to the change in CSA from one airway
generation to the next, i.e., convective acceleration (CA). Pressure
gradient due to convective acceleration (PCA) is
calculated as
|
(10) |
PLaminar,
PTurbulent, and PCA are estimated from
the lobar bronchi (z = 2) to z = 12;
total pressure drop across the left lower lobe (PLLL) is
their sum
|
(11) |
PLLL) and lobar flow (LLL) can then
be derived for increasing levels of flow where
K1 and K2 are empiric
quadratic coefficients
|
(12) |
) is estimated
by using Otis's model (22) for the left lower lobe alone
and for the entire lung in Sham and PNX groups by assuming a sinusoidal
flow pattern
|
(13) |
Statistical analysis. Volume data were normalized to body weight and expressed as means ± SE. Airway dimensions were plotted with respect to generations z = 1-12. Estimated pressure drops and work of breathing were plotted against lobar flow rates. Tracheal dimensions were compared separately. Group comparisons at each time point were done by two-way ANOVA. All 4- to 10-mo comparisons were performed by using 1) data from all available animals compared by two-way ANOVA or 2) only data from three animals per group that had repeat studies at both time points compared by repeated-measures ANOVA. Results showed similar significance levels by either approach and did not alter any conclusion. Hence we elected to show all available data from all animals in the table and figures (n = 5 PNX, n = 6 Sham at 4 mo; n = 3 per group at 10 mo). A commercial software program (Statview v.5, SAS Institute, Cary, NC) was used. A P value of <0.05 was considered significant.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Figure 1 shows examples of CT images
demonstrating the mediastinal shift and expansion of the left lung
after right PNX. Figure 2 shows a wire
frame reconstruction of conducting airways of the left lower lobe,
demonstrating the prominent airway rotation and splaying post-PNX.
These anatomical changes are qualitatively similar at 4 and 10 mo after
PNX. Body weight, total lung air, and tissue volumes and central airway
calibers are shown in Table 1. Mean body
weight at 10 mo was higher in the PNX group at a borderline
significance (P = 0.08); however, the average weight gain among 6 animals that had repeat studies at 4 and 10 mo after surgery was not significantly different between groups (64 ± 11% for PNX and 42 ± 13% for Sham group, P = 0.25 by
repeated-measures ANOVA). At both time points, air and tissue volumes
of the left lung were twofold higher in PNX animals compared with
respective controls, consistent with compensatory septal tissue growth.
Tracheal lengths were similar between groups at 4 and 10 mo after PNX. Tracheal CSA increased significantly more from 4 to 10 mo after surgery
in the PNX animals than in Sham controls (45 and 22%, respectively).
Tracheal CSA was not different between groups at 4 mo but was
significantly larger (by 21%) after PNX compared with Sham at 10 mo
(P < 0.0025). Thus, tracheal dilatation occurred beyond 4 mo after PNX. The left main stem bronchus was longer after PNX
compared with Sham, although the difference only reached statistical
significance at 4 mo. Mean CSA of the left main stem bronchus was
similar between groups at 4 mo. By 10 mo CSA had increased
significantly in the PNX group compared with Sham.
|
|
|
Distal to about the eighth generation, the number of visualized airways
progressively decreased with each generation; our data represent only
the mean dimensions of visualized branches. Airways distal to the 12th
generation were visualized in some but not all animals; hence
measurements from these distal airways were excluded from analysis.
Cumulative airway lengths from main stem bronchus to generation
12 (Fig. 3) were significantly
longer at both 4 and 10 mo after PNX (by 11%) compared with Sham
animals. Lobar airway CSA increased from 4 to 10 mo in both groups; the relative increase was greater in PNX animals than in Sham animals (Fig.
4, P < 0.01 for all
between-group comparisons).
|
|
Estimated pressure gradients and work of breathing.
At 4 mo after surgery, the estimated pressure gradient across the left
lower lobe (PLLL, z = 2-12) at any
given flow rate was not significantly different between groups (Fig.
5). By 10 mo, PLLL
estimated for a given flow rate declined significantly in both groups;
however, for a given lobar flow, the PLLL for the PNX
animals was significantly lower by ~50% than in Sham animals (P < 0.0001), indicating a greater reduction of airway
resistance in PNX animals than can be explained by normal lung
maturation. Thus there has been an unequivocal compensatory reduction
in lobar Raw with time after PNX.
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Summary of findings. These are the first in vivo measurements of airway dimensions after PNX made under physiological conditions at normal distending pressures. In keeping with previous observations (29), we found that by 4 mo after PNX, air and tissue volumes of the remaining lung equaled that of both lungs in Sham controls. Delayed tracheal dilatation occurred between 4 and 10 mo after PNX, whereas tracheal length did not increase more than expected from maturation. Airway lengths increased more in PNX than in Sham animals at both time points. Between 4 and 10 mo, airway CSA increased more in PNX animals. By 10 mo after PNX, average CSA of a given generation in the left lower lobe was 24% higher than in the same generation of control animals. At 4 mo after PNX, estimated lobar pressure gradient due to Raw was not different from controls, but it was significantly lower by 10 mo after PNX. Even though there was no further increase in body mass-specific lung volume, progressive airway dimensional changes after PNX can theoretically account for a net 50% reduction in lobar Raw compared with that expected through the normal lobe at the same volume flow.
Interpretation of findings. There are at least three reasons for Raw to be elevated after PNX: 1) Total airway CSA is reduced by 55-58% after PNX. Subsequent airway dilatation increased average CSA by 24%, but total CSA still remains below that expected in two normal lungs. 2) Airway lengthening further increases Raw after PNX. 3) At any given total ventilation, volume flow through the remaining airways is ~1.72 times that through the airways of two control lungs; i.e., resistance due to turbulence and convective acceleration between successive airway generations in the remaining lung after PNX should increase by ~(1.72)2 = 2.96-fold. As a result, measured airway dimensional changes would cause ~50% reduction in lobar Raw but only ~30% net reduction in estimated work of breathing against Raw in the whole animal (Fig. 6). This analysis provides an anatomical explanation for our previous observation of a persistently elevated resistance after PNX. Early after PNX, airway lengthening and minimal dilatation offset each other, and we can expect little compensation for the increased Raw. Thereafter, progressive airway dilatation attenuates lobar Raw but did not achieve a sufficient magnitude to normalize total Raw or work of breathing in the whole animal. This analysis predicts that work of breathing against Raw at 10 mo after PNX would be ~3 to 3.5-fold higher than in controls. These results are consistent with our previous physiological measurements in pneumonectomized puppies studied at maturity 10-12 mo later showing a 2- to 2.5-fold higher work of breathing done against the whole lung at rest and during exercise compared with matched controls (27).
Critique of methods. Because airway lengthening and dilatation exert opposing influences on Raw, functional significance of these anatomic alterations cannot be interpreted without a formal framework. However, there are limitations in calculating Raw from CT data. We used the well-established model by Rohrer (19, 24) based on measured airway dimensions from trachea to airways 1 mm in diameter in a human lung, which yielded pressure-flow relationships close to those actually measured in the human lung (7, 20). We assumed that air is an incompressible fluid and that adaptive changes are similar in all the remaining lobes of the left lung. We have subsequently compared the relative lobar expansion after PNX by CT scan and found this assumption to be reasonable (unpublished observations). In addition, we did not take into account the effect of airway distortion after PNX, which if added would have made compensation even less complete and would have further strengthened our conclusion.
The bifurcation pattern of the canine and human conducting airway tree is in fact asymmetric and fractal (13, 14, 25), even though symmetry has been widely assumed in the literature when applying anatomic data to estimate flow and pressure. We assumed the symmetrical model (30), which greatly simplifies calculation but may lead to systematic errors. Asymmetric airway bifurcation gives rise to one dominant and one smaller daughter branch. The dominant branch could be followed to at least generation 12, whereas the smaller daughter branches disappear sooner. There is a large variation in the length and diameter within a given airway generation, and the number of visualized airways did not continue to increase beyond about generation 6. Thus our results of average CSA in the distal airway generations (z = 6-12) are overestimated. However, this bias occurs across all groups, so the comparison among groups remains valid. In addition, potential error in estimated resistance of these distal generations contributes very little to overall airway resistance. Despite these simplifying assumptions, this model yields estimates of pressure gradient and work of breathing consistent with actual measurements obtained from exercising dogs (15).Airway function of after PNX. Arnup et al. (1) showed in immature dogs 16 wk after left PNX that maximum expiratory flow rate during forced expiration is reduced by ~60%. The magnitude of flow reduction is more than expected from the loss of CSA of central airways alone. Greville et al. (10) and Georgopoulos et al. (8) applied wave-speed theory and found that the reduced maximum flow rate after PNX is associated with 1) a more peripheral location of the choke point, which develops at lower flows and transmural pressures, and 2) an increased upstream frictional resistance. They attributed 60% of the post-PNX reduction in maximal flow rate to changes in dynamic central airway properties and 40% to increased lobar frictional resistance. Although there are lobar differences in airway mechanical properties after PNX, Mink et al. (21) found relatively uniform lobar emptying rates over most of vital capacity, attributed to the interdependence of maximum lobar expiratory flows. These data indirectly suggest that compensatory airway growth is not as extensive as parenchymal growth. Greville et al. (10) did not find a change in central airway diameters after PNX in dog lungs dried at a constant distending pressure.
We have shown that the long-term ventilatory power requirement at a given minute ventilation in dogs after PNX is significantly elevated during exercise as a result of increased elastic as well as viscous resistances of the remaining lung compared with that in both lungs of normal animals (15, 27, 28). The elevation in ventilatory power requirement is greater after 55-58% resection by right PNX than after 42-45% resection by left PNX (15). The magnitude of long-term increases in ventilatory power requirement is similar regardless of the maturity of the animal at the time of lung resection (27). In contrast, long-term pulmonary gas-exchange function during exercise is completely normalized in animals pneumonectomized as puppies but only partially normalized in animals pneumonectomized as adults. These functional studies also indicate a more vigorous compensatory response of the parenchyma than that of the airways.Anatomy of conducting airways after PNX. Available literature suggests that conducting airways can remodel and grow in response to PNX, but the extent and nature of growth varies with experimental techniques, species, and maturational stages. Boatman (3) studied bronchial casts in pneumonectomized rabbits and found that axial airway length increased compared with control rabbits but airway diameters did not change. Yee and Hyatt (32) studied tantalum bronchograms of excised lungs from pneumonectomized rabbits and found that central airways lengthened in proportion to the increase in lung volume. Burri and Sehovic (5) applied morphometric techniques to the fixed lung from pneumonectomized rats and found that volume of the conducting airways increased less than the volume of the parenchyma. McBride and co-worker (17, 18) quantified airway dimensions by using silicone bronchial casts of lungs from pneumonectomized immature ferrets raised to maturity and reported a 12-20% increase in CSA and cumulative airway length, the latter due to lengthening of distal airways with little change in proximal airway dimensions. The increase in airway CSA at all levels was less than expected from the increase in lung volume after PNX. These data support a dissociated response; i.e., compensatory airway growth lags behind parenchymal growth. This pattern, termed dysanaptic (i.e., unequal growth) by Green et al. (9), was originally invoked to interpret the large interindividual variation in maximal expiratory flow rate relative to lung volume. The term was later applied by Brody et al. (4) to explain the discordant changes between lung volume and maximal flow rate observed in high-altitude natives.
Time course and mechanisms of airway response. Our striking finding is the slow but progressive nature of airway remodeling. Early after PNX, conducting airways lengthened without significant dilatation; these changes cause little compensatory reduction in Raw even as the septal tissues are actively proliferating. Airway dilatation became evident between 4 and 10 mo after PNX, after compensatory septal cell growth had already caught up with septal growth in Sham animals. Airway CSA of central and distal generations increased significantly by 10 mo after PNX consistent with postmortem findings by McBride (18). This slow response may explain why Greville et al. (10) failed to observe any change in central airway caliber in dried, inflated lungs 16 wk after PNX.
That airways are stimulated to grow and remodel after PNX is not surprising. Cagle and Thurlbeck (6) pointed out that bronchial epithelial cells as well as alveolar septal cells multiply during compensatory lung growth. Mesothelial cells appear to proliferate first, and peripheral alveolar tissue proliferates before central alveolar tissue. Thus the general scheme of compensatory response proceeds from the peripheral toward the central regions of the remaining lung. The peripheral alveolar tissue can grow easily by adding new septa, increasing the complexity of the existent septa, and perhaps forming another generation of alveolar ducts. Respiratory bronchioles also increase in number after PNX in conjunction with septal tissue growth (16). Assuming that the branching pattern of acinar airways is fully established at birth, acinar airways can increase in number via either 1) transformation of the first generation of alveolar ducts into respiratory bronchioles or 2) alveolarization of the terminal bronchiole. The ability for anatomical growth of more proximal conducting airways is more restricted; essentially lengthening and dilatation are the only options. Remodeling involving these large and rigid structures would likely require more time than remodeling of small and more compliant structures such as the alveoli. Sustained mechanical stress is an important signal for compensatory alveolar tissue growth (31) and likely also plays an important role in airway remodeling after PNX. Airway lengthening after PNX is essential to provide structural support for the expanding remaining lung; lengthening also reduces longitudinal airway stress associated with lung expansion but occurs at the expense of an increased airflow resistance. On the other hand, chronically increased flow through the remaining airways may stimulate airway pressure and/or flow receptors, leading to relaxation of airway smooth muscles and a larger in vivo airway diameter, which decreases flow resistance. The more negative intrathoracic pressure after PNX exerts radial traction on the airways that may also facilitate airway dilatation. Because Raw is inversely proportional to the fourth power of airway diameter and directly related to airway length, only a minimal increase in distal airway diameter is needed to substantially reduce flow resistance and offset the effect of airway lengthening. In contrast to distal airways, the trachea and main stem bronchi are less compliant and less adaptable. These central cartilaginous airways experience a lower strain at a given lung stress or stretch; hence strain-induced response is also blunted. Whether chronically increased airflow permanently alters the physiological properties of airway smooth muscle or their ability to constrict cannot be answered from the present study. We conclude that in immature dogs after removing 55-58% of the conducting airways by right PNX, lengthening of the remaining airways occurs early whereas airway dilatation becomes evident later, resulting in delayed partial compensation of Raw and work of breathing. The modest post-PNX increase in average airway CSA (~25% above Sham) significantly reduces the expected lobar flow resistance by ~50%, although it is still insufficient to completely normalize Raw of the whole animal. Airway remodeling continues even after compensatory septal tissue proliferation is complete. Dilatation or elongation must have been accompanied by the addition of new airway tissue or by a reduction in airway compliance. These structural changes exaggerate the postnatal maturational pattern. We cannot rule out the possibility that progressive airway remodeling and functional compensation may continue even beyond 10 mo after PNX.| |
ACKNOWLEDGEMENTS |
|---|
The authors gratefully acknowledge Dr. Robert Parkey for making available the facilities of the Radiology Department and Dr. Roderick W. McColl for assistance with data transfer.
| |
FOOTNOTES |
|---|
This project was supported by National Heart, Lung, and Blood Institute Grants R01 HL-40070, HL-54060, HL-45716, and HL-62873.
Address for reprint requests and other correspondence: C. C. W. Hsia, Pulmonary and Critical Care Medicine, Dept. of Internal Medicine, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9034.
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.
June 21, 2002;10.1152/japplphysiol.00970.2001
Received 21 September 2001; accepted in final form 28 May 2002.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Arnup, ME,
Greville HW,
Oppenheimer L,
Mink SN,
and
Anthonisen NR.
Dynamic lung function in dogs with compensatory lung growth.
J Appl Physiol
57:
1569-1576,
1984.
2.
Barnas, GM,
Stamenovic D,
Lutchen KR,
and
MacKenzie CF.
Lung and chest wall impedances in the dog: effects of frequency and tidal volume.
J Appl Physiol
72:
87-93,
1992.
3.
Boatman, ES.
A morphometric and morphological study of the lungs of rabbits after unilateral pneumonectomy.
Thorax
32:
406-417,
1977.
4.
Brody, JS,
Lahiri S,
Simpser M,
Motoyama EK,
and
Velasquez T.
Lung elasticity and airway dynamics in Peruvian natives to high altitude.
J Appl Physiol
42:
245-251,
1977.
5.
Burri, PH,
and
Sehovic S.
The adaptive response of the rat lung after bilobectomy.
Am Rev Respir Dis
119:
769-777,
1979.
6.
Cagle, PT,
and
Thurlbeck WM.
Postpneumonectomy compensatory lung growth.
Am Rev Respir Dis
138:
1314-1326,
1988.
7.
DuBois, AB.
Resistance to breathing.
In: Handbook of Physiology: Respiration. Bethesda, MD: Am. Physiol. Soc, 1964, sect. III, vol. 1, chapt. 16, p. 451-462.
8.
Georgopoulos, D,
Mink SN,
Oppenheimer L,
and
Anthonisen NR.
How is maximal expiratory flow reduced in canine postpneumonectomy lung growth?
J Appl Physiol
71:
834-840,
1991.
9.
Green, M,
Mead J,
and
Turner JM.
Variability of maximum expiratory flow-volume curves.
J Appl Physiol
37:
67-74,
1974.
10.
Greville, HW,
Arnup ME,
Mink SN,
Oppenheimer L,
and
Anthonisen NR.
Mechanism of reduced maximum expiratory flow in dogs with compensatory lung growth.
J Appl Physiol
60:
441-448,
1986.
11.
Hibbert, M,
Lannigan A,
Raven J,
Landau L,
and
Phelan P.
Gender differences in lung growth.
Pediatr Pulmonol
19:
129-134,
1995.
12.
Hopper, JL,
Hibbert ME,
Macaskill GT,
Phelan PD,
and
Landau LI.
Longitudinal analysis of lung function growth in healthy children and adolescents.
J Appl Physiol
70:
770-777,
1991.
13.
Horsfield, K.
Diameters, generations, and orders of branches in the bronchial tree.
J Appl Physiol
68:
457-461,
1990.
14.
Horsfield, K,
and
Cumming G.
Morphology of the bronchial tree in the dog.
Respir Physiol
26:
173-182,
1976.
15.
Hsia, CCW,
Herazo LF,
Ramanathan M,
Claassen H,
Fryder-Doffey F,
Hoppeler H,
and
Johnson RL, Jr.
Cardiopulmonary adaptations to pneumonectomy in dogs. III. Ventilatory power requirements and muscle structure.
J Appl Physiol
76:
2191-2198,
1994.
16.
Hsia, CCW,
Zhou XS,
Bellotto DJ,
and
Hagler HK.
Regenerative growth of respiratory bronchioles in dogs.
Am J Physiol Lung Cell Mol Physiol
279:
L136-L142,
2000.
17.
Kirchner, KK,
and
McBride JT.
Changes in airway length after unilateral pneumonectomy in weanling ferrets.
J Appl Physiol
68:
187-192,
1990.
18.
McBride, JT.
Postpneumonectomy airway growth in the ferret.
J Appl Physiol
58:
1010-1014,
1985.
19.
Mead, J.
Translations in Respiratory Physiology. Stroudsburg, PA: Dowden, Hutchenson and Ross, 1975.
20.
Mead, J,
and
Agostoni E.
Dynamics of breathing.
In: Handbook of Physiology: Respiration. Bethesda, MD: Am. Physiol. Soc, 1964, sect. III, vol. 1, chapt. 16, p. 411-428.
21.
Mink, SN,
Holtby SG,
Berezanski DJ,
Oppenheimer L,
and
Anthonisen NR.
Heterogeneity of maximal lobar emptying rates in dogs with compensatory lung growth.
J Appl Physiol
67:
1164-1170,
1989.
22.
Otis, AB.
The work of breathing.
In: The Handbook of Physiology: Respiration. Bethesda, MD: Am. Physiol. Soc., 1964, sect. III, vol. 1, chapt. 17, p. 463-476.
23.
Rahn, H,
Sadoul P,
Farhi LE,
and
Shapiro J.
Distribution of ventilation and perfusion in the lobes of the dog's lung in the supine and erect position.
J Appl Physiol
8:
417-426,
1956.
24.
Rohrer, F.
Der Stromungswidestand in den menschlichens Atemwegen und Verzweigung des Bronchialsystems auf den Atmungsverlaf in verschiedenen Lungenbezirken.
Pflügers Arch
162:
225-229,
1915.
25.
Ross, BB.
Influence of bronchial tree structure on ventilation in the dog's lung as inferred from measurements of a plastic cast.
J Appl Physiol
10:
1-14,
1957.
26.
Takeda, S,
Hsia CCW,
Wagner E,
Ramanathan M,
Estrera AS,
and
Weibel ER.
Compensatory alveolar growth normalizes gas exchange function in immature dogs after pneumonectomy.
J Appl Physiol
86:
1301-1310,
1999.
27.
Takeda, S,
Ramanathan M,
Estrera AS,
and
Hsia CCW
Postpneumonectomy alveolar growth does not normalize hemodynamic and mechanical function.
J Appl Physiol
87:
491-497,
1999.
28.
Takeda, S,
Ramanathan M,
Wu EY,
Estrera AS,
and
Hsia CCW
Temporal course of gas exchange and mechanical compensation after right pneumonectomy in immature dogs.
J Appl Physiol
80:
1304-1312,
1996.
29.
Takeda, S,
Wu EY,
Epstein RH,
Estrera AS,
and
Hsia CCW
In vivo assessment of changes in air and tissue volumes after pneumonectomy.
J Appl Physiol
82:
1340-1348,
1997.
30.
Weibel, ER.
Morphometry of the Human Lung. New York: Academic, 1963.
31.
Wu, EY,
Hsia CCW,
Estrera AS,
Epstein RH,
Ramanathan M,
and
Johnson RL, Jr.
Preventing mediastinal shift after pneumonectomy does not abolish physiological compensation.
J Appl Physiol
89:
182-191,
2000.
32.
Yee, NW,
and
Hyatt RE.
Effect of left pneumonectomy on lung mechanics in rabbits.
J Appl Physiol
54:
1612-1617,
1983.
This article has been cited by other articles:
|
|
 |
|
  C. C. W. Hsia, D. M. Dane, A. S. Estrera, H. E. Wagner, P. D. Wagner, and R. L. Johnson Jr. Shifting sources of functional limitation following extensive (70%) lung resection J Appl Physiol, April 1, 2008; 104(4): 1069 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fehrenbach, R. Voswinckel, V. Michl, T. Mehling, A. Fehrenbach, W. Seeger, and J. R. Nyengaard Neoalveolarisation contributes to compensatory lung growth following pneumonectomy in mice Eur. Respir. J., March 1, 2008; 31(3): 515 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Friedrich, P. M. C. Pitrez, R. T. Stein, M. Goldani, R. Tepper, and M. H. Jones Growth Rate of Lung Function in Healthy Preterm Infants Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1269 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wongtrakool, S. Roser-Page, H. N. Rivera, and J. Roman Nicotine alters lung branching morphogenesis through the {alpha}7 nicotinic acetylcholine receptor Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L611 - L618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ravikumar, C. Yilmaz, D. M. Dane, R. L. Johnson Jr., A. S. Estrera, C. C. W. Hsia, and (With the Technical Assistance of Richard T. Hogg Developmental signals do not further accentuate nonuniform postpneumonectomy compensatory lung growth J Appl Physiol, March 1, 2007; 102(3): 1170 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. W. Hsia Quantitative morphology of compensatory lung growth Eur. Respir. Rev., December 1, 2006; 15(101): 148 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. V. Winkle, M. V. Fanucchi, L. A. Miller, G. L. Baker, L. J. Gershwin, E. S. Schelegle, D. M. Hyde, M. J. Evans, and C. G. Plopper Epithelial cell distribution and abundance in rhesus monkey airways during postnatal lung growth and development J Appl Physiol, December 1, 2004; 97(6): 2355 - 2363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. W. Hsia Signals and mechanisms of compensatory lung growth J Appl Physiol, November 1, 2004; 97(5): 1992 - 1998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Mitzner and E. M. Wagner Vascular remodeling in the circulations of the lung J Appl Physiol, November 1, 2004; 97(5): 1999 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Mechanisms and Limits of Induced Postnatal Lung Growth Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 319 - 343. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Dane, X. Yan, R. M. Tamhane, R. L. Johnson Jr., A. S. Estrera, D. C. Hogg, R. T. Hogg, and C. C. W. Hsia Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy J Appl Physiol, March 1, 2004; 96(3): 1090 - 1096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. W. Hsia, R. L. Johnson Jr, E. Y. Wu, A. S. Estrera, H. Wagner, and P. D. Wagner Reducing lung strain after pneumonectomy impairs oxygen diffusing capacity but not ventilation-perfusion matching J Appl Physiol, October 1, 2003; 95(4): 1370 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. W. Hsia, X. Yan, D. M. Dane, and R. L. Johnson Jr. Density-dependent reduction of nitric oxide diffusing capacity after pneumonectomy J Appl Physiol, May 1, 2003; 94(5): 1926 - 1932. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||
) compared with Sham (
). By 10 mo
after PNX (
), airway dimensional changes would have
decreased work of breathing to 30% below corresponding Sham values
(
), indicating functional improvement in the left lung.
In reality, the Sham left lung receives only ~42% of tracheal flow.
When the data were analyzed with the tracheal flow divided through two
Sham lungs (crosses), work of breathing in the whole animal after PNX
remained significantly above Sham values at both time points; the
magnitude of increase became attenuated with time (6-fold at 4 mo vs.
3.5-fold at 10 mo). Thus the observed airway dimensional changes after
PNX should significantly reduce Raw of the remaining lung but was
unlikely to normalize total Raw or work of breathing in the whole
animal.