| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Pediatrics, 2 Department of Physiology and Biophysics and 3 Division of Biostatistics, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Our laboratory has previously demonstrated that maximal bronchoconstriction produces a greater degree of airway narrowing in immature than in mature rabbit lungs (33). To determine whether these maturational differences could be related to airway structure, we compared the fraction of the airway wall occupied by airway smooth muscle (ASM) and cartilage, the proportion of wall area internal to ASM, and the number of alveolar attachments to the airways, from mature and immature (6-mo- and 4-wk-old, respectively) rabbit lungs that were formalin fixed at total lung capacity. The results demonstrate that the airway walls of immature rabbits had a greater percentage of smooth muscle, a lower percentage of cartilage, and fewer alveolar attachments compared with mature rabbit airways; however, we did not find maturational differences in the airway wall thickness relative to airway size. We conclude that structural differences in the airway wall may contribute to the greater airway narrowing observed in immature rabbits during bronchoconstriction.
maturation; lung growth
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
PREVIOUS STUDIES HAVE SHOWN that bronchoconstriction with methacholine produces a greater increase in pulmonary resistance in immature than in mature rabbits (33, 34). This maturational difference in the effect of methacholine on lung resistance is primarily caused by greater airway narrowing in the immature rabbits (31). The mechanisms for the maturational differences in airway narrowing remain unclear. The degree of airway narrowing depends on the smooth muscle shortening, the structure of the airway wall, and its interaction with the lung parenchyma. The magnitude of smooth muscle shortening is determined by a balance of two forces: the force generated by the airway smooth muscle (ASM) and the forces that limit ASM shortening (13, 15, 22, 43). A greater amount of ASM within the airway wall could increase the force generation and thus increase airway narrowing in immature rabbits. Conversely, less cartilage in the airway wall could result in a more compliant airway and greater airway narrowing. In addition, fewer alveolar attachments to the immature airway wall could decrease the forces of interdependence between the airways and the lung parenchyma and could thus decrease the load that ASM must shorten against. Furthermore, geometric factors, such as the thickness of the airway wall internal to the ASM relative to the airway diameter, can also affect the degree of airway narrowing. For the same degree of ASM shortening, a proportionately thicker airway wall internal to the ASM will amplify the effect of any smooth muscle shortening and thus lead to greater airway narrowing (22).
Our laboratory has previously determined that there is greater airway narrowing in the immature than the mature rabbit lung (33). The purpose of the present study was to determine whether there were structural differences in the airways of immature and mature animals that may account for these functional differences. In this study, we compared the following airway morphometric characteristics, which might contribute to greater airway narrowing in immature rabbits: 1) the fraction of airway wall occupied by ASM; 2) the fraction of airway wall occupied by cartilage; 3) the ratio of wall area internal to the ASM relative to the area of the airway; and 4) the number of alveolar attachments to the airways.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
A total of 11 immature (4-6 wk, 0.5-0.6 kg) and 10 mature (6 mo, 2.5-2.7 kg) New Zealand White rabbits were studied. Animals were anesthetized with pentobarbital sodium (50 mg/kg body wt) and then exsanguinated by severing of the abdominal artery. The intact lungs were then excised and degassed under vacuum. A canula was tied to the proximal portion of the trachea, and the lungs were inflated with 10% formalin to a distending pressure of 20 cmH2O. The lungs were fixed at 20 cmH2O for 4 days using a recirculating pump, after which the lungs were immersed in 10% formalin for an additional 3 days to ensure complete fixation of the tissue. Two preparations were used: 1) isolated airway preparation and 2) whole lung preparation. The distending pressure of 20 cmH2O was chosen so that the airways would be maximal in size (to minimize mucosal folding) and would be nearly circular, which would minimize identifying airways cut longitudinally vs. buckled airways at lower transpulmonary pressures. In addition, our previous data indicate that maximal diameter is actually achieved above 10 cmH2O.
Isolated Airway Preparation
To compare the structural characteristics of the airways from immature and mature rabbits, we isolated the airways of comparable anatomic location from six immature and five mature rabbits. The lung parenchyma was scraped from the main axial pathway of the right lung, and the isolated airway was divided into eight segments, each representing a generation. Each segment was the portion of the axial pathway between two successive major branches arising from the primary axial pathway. The trachea was numbered generation 1, and the most distal isolated portion of the right axial pathway was generation 8 (Fig. 1). Each airway segment was individually embedded in paraffin, and 5-µm-thick sections were cut from each paraffin block and stained using Masson's Trichrome technique. Sections were cut from the distal portion of each segment to minimize the variability associated with sampling across generations and rabbits. Airway sections in which the ratio of the largest to smallest diameter was >2 were excluded to minimize using airways that had not been sectioned perpendicular to the longitudinal axis. We excluded six immature and four mature airways that did not fit this criterion. In addition, the ratio of larger to smaller diameters for airways included for analysis did not differ for the immature and mature animals. Airway sections were visualized by light microscopy, and images were captured using a digital camera (DC-120, Kodak, Rochester, NY) coupled to the microscope. Morphometric analysis of the images was performed using an imaging software program (Metamorph, version 2.76, Universal Imaging), with computer-assisted tracing of the internal perimeter and airway wall thickness.
|
Morphometric Measurements
Airway dimensions.
The following measurements of airway dimensions were obtained from
sections of each airway generation: 1) internal perimeter of
the airway defined by the luminal border of the airway epithelium (Pi) and 2) airway inner wall
thickness (Ti), from the outer border of the
smooth muscle to the luminal border of the epithelium (Fig. 2). Pi was traced
from images taken at a magnification that included the entire cross
section of the airway. We calculated the area circumscribed by this
perimeter rather than directly measuring the lumen area. We used this
approach to minimize the possible underestimation of the lumen area in
the airways that were not circular due to deformation (collapse) of the
airway lumen that might have occurred during the embedding and
subsequent processing. The magnifications used for the perimeter were
not high enough for detailed morphometric measurements due to the
thinness of the rabbit airway wall relative to the airway diameter.
Therefore, each airway was divided into four quadrants, and the
midportion of each quadrant was systematically imaged at a higher
magnification for airway thickness measurements. Thus the thickness
measurements for each airway are an average value of the images from
the four quadrants. The following parameters were calculated from the
measurements of Pi and
Ti: the internal radius
(ri) was calculated as
Pi/2
, and the internal diameter
(Di) was calculated as
2ri. The fully relaxed internal area
(Ai) was calculated as
Pi2/4. the area enclosed
by the outer border of the muscle (Amo) was
calculated as (Rmo)2 where
|
(1) |
|
(2) |
|
Airway wall composition. For each of the isolated airways taken from the six immature and five mature rabbits, the fractions of the airway wall occupied by ASM and cartilage were determined by point counting (41). A 10 × 10 grid was superimposed on the downloaded image of the airway on the computer screen using the Metamorph software. Each of the digitized images was taken from the four quadrants for each airway. The value reported for each airway was determined by averaging measurements from the four quadrants. The percentage of the wall components for each airway was estimated by counting the number of points of intersection for each of the components and then expressed as a fraction of the total number of components (total airway wall).
In a subset of the sample, point counting was done in triplicate to determine the reproducibility of the measurements. The average percent coefficient of variation for the measurements of percent muscle was 5.0% and for percent cartilage was 3.6%.Whole Lung Preparation
Alveolar attachments and airway dimensions. To evaluate the number of attachments to the intraparenchymal airways, the formalin-fixed right lungs from five immature and five mature rabbits were cut into five, equally spaced, transverse sections (referred to as whole lung preparation). Each piece was then embedded in paraffin, sectioned, stained, and visualized under a light microscope. Digital images were captured as described in Isolated Airway Preparation. Airways with a ratio of largest to smallest diameters >2 were excluded. Each airway image was visually inspected, and the number of alveolar attachments was counted around the outer perimeter using the Metamorph software. Pi was measured as previously described for the isolated airway preparation.
Statistical Analysis
Repeated-measures ANOVA was used to evaluate maturational differences in the outcome variables across all generations of isolated airways (16). Included in these models were linear effects of generation. For muscle and cartilage, we also included a quadratic effect for generation, as was indicated graphically. An overall P value for differences between mature and immature rabbits was calculated for each of the response variables (Di, Ti, PWAi, percent cartilage, and percent muscle). The relationship between the number of alveolar attachments and Pi was modeled using a repeated-measures ANOVA model, with the logarithm of the number of attachments as the response and the logarithm of Pi and maturity as predictor variables. We tested for a difference in slopes between mature and immature rabbits by including the maturity by perimeter interaction.| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Mean Di and Ti for
immature and mature rabbits are plotted as functions of generation in
Fig. 3, A and B. Di and Ti decreased with
increasing generation for both immature and mature airways. Airways
from the mature rabbits had larger absolute Di
(P < 0.001) and greater Ti
(P < 0.002) compared with those from immature rabbits. PWAi increased with increasing generation for both age
groups; however, the difference in PWAi in airways from the
immature and mature rabbits across generations was not statistically
significant (P = 0.24; Fig.
4). As an exploratory analysis, we
examined the wall areas seen in Fig. 4 in greater detail. There was no
evidence that a difference existed at generations 2,
3, 4, 6, 7, and
8 (P > 0.1 for all). At generation
5, there was slight evidence that mature rabbits tended to have
larger wall areas (P = 0.0149, unadjusted for multiple
testing). A likely reason for not observing differences at other
generations was lack of power due to small sample sizes, with estimated
power ranging between 5 and 31%.
|
|
The percentage of the airway wall occupied by smooth muscle increased
from the central to the more peripheral airways for both groups (Fig.
5). The mean percentage of ASM across
generations was greater in the immature than in the mature airways, and
the difference approached statistical significance (P = 0.06). In contrast to the increase in ASM with generation, the
percentage of cartilage in the airway wall decreased as generation
number increased, for both groups (Fig.
6). In addition, the immature rabbits had
a smaller mean percentage of cartilage across generations compared with
mature rabbits (P = 0.03).
|
|
A total of 56 immature and 152 mature airways were analyzed from the
whole lung sections. The number of alveolar attachments increased with
increasing Pi, as seen for the log-transformed data for both mature and immature airways (P < 0.0001;
Fig. 7). For the same airway size, the
immature rabbits tended to have fewer attachments (P = 0.07), but there was no evidence that the relationship between the
number of alveolar attachments and Pi differed
between mature and immature rabbits (P = 0.59).
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The results of the present study demonstrate that there are structural differences in the anatomically similar airways of mature and immature rabbits that may contribute to the greater airway narrowing previously observed in these animals (33). The airway walls of immature rabbits have proportionately more smooth muscle, which could result in greater force generation and shortening. A lower percentage of cartilage was also observed in the airway wall of immature rabbits compared with mature rabbits. This difference could also contribute to greater airway narrowing in the immature animal by providing a lower load during shortening of the smooth muscle. The immature rabbit airways also had fewer alveolar attachments compared with mature rabbit airways, which could result in decreased interdependence between the airways and the lung parenchyma in immature animals, and thus a smaller load to resist ASM shortening. We did not find that immature airways have greater airway Ti relative to airway size for comparable airway generations. This suggests that geometric factors, such as a relatively thicker wall, may not contribute to the greater airway narrowing in immature rabbits.
ASM
The proportionately greater ASM in the airway wall of the immature than the mature rabbits may be a basis for our laboratory's previous findings of greater airway narrowing in immature animals. Computational models of airway narrowing have demonstrated that the degree of airway narrowing is linearly related to the proportion of smooth muscle in the airway wall (22). Our findings of a relationship between the proportion of smooth muscle in the airway wall and the amount of airway narrowing in immature and mature rabbits is consistent with studies assessing the relationship between the proportion of ASM and airway narrowing in mature animals of different species. Martin and co-workers (18) reported that a higher proportion of ASM within the airway wall correlated with greater maximal increases in airway narrowing across different mammalian species.There are few studies that have evaluated maturational differences in the quantity of ASM in the airway wall. Matsuba and Thurlbeck (19) compared the quantity of ASM in the airways of human children and adults. These investigators found that the proportion of ASM in large airways was similar in the two groups, but that the children had a smaller proportion of ASM in the smaller airways. Although the reasons for the differences in overall trend in our study and that of the human study could be many, one of them could be attributed to differences in the method of classification of the studied airways. In our study of rabbits, we evaluated anatomically comparable airways. In contrast, the human airways were grouped as major bronchi or airways <2 mm in diameter; thus the airways were not anatomically matched. In a study of swine (23), the percent of ASM in the airway wall was compared in 2- to 10-wk-old animals through generations 2 to 4 and was found to be similar; however, airway rings from the 2-wk-old animals produced greater maximal tension. In swine, there were no differences in percent smooth muscle in generations 0-5 in 2- and 10-wk-old animals (23). We found that the proportion of ASM within the airway wall increased within the more distal generations in both age groups, a finding that is similar to observations in humans (19, 32, 39). Therefore, the swine airway may be structurally different than those of humans and rabbits and thus may have a different relationship between structure and function with respect to airway reactivity.
Cartilage
In our study, there was a smaller proportion of cartilage in the airway wall of the immature than the mature rabbits. This finding is consistent with the observations of maturational differences in the structure of airways in sheep (6, 29). In humans, one study reported a lower fraction of cartilage in the airway walls of infants than adults (11); however, another study found no maturational differences in cartilage in the airway wall (19). A lower proportion of cartilage could result in a more compliant airway wall. Studies of airways from rabbits, humans, and several other species have found that immature animals have more compliant airways (4-6, 8, 20, 27, 29).Cartilage provides structural support to the airway wall and is an elastic load that resists airway narrowing. In rabbits, softening of the cartilage tissue by administration of intravenous papain increases the maximal airway response to acetylcholine (21). This suggests that increasing the compliance of the cartilage decreases the load that the ASM shortens against and results in greater airway narrowing. Cartilage can provide a preload that determines ASM length, as well as an afterload during ASM shortening. When tracheal smooth muscle shortens, the horseshoe-shaped cartilage is deformed away from its resting position, creating an elastic load that opposes ASM shortening (9). In intrapulmonary bronchi, overlapping of the cartilage plates can also provide a significant load to ASM shortening (26, 39). Maturational differences in the quantity of cartilage within the airway wall may affect airway narrowing by altering the elastic pre- and afterload, such as when the cartilaginous plates overlap and limit airway narrowing.
Ti and Ai
PWAi increased in the more distal airways in both immature and mature rabbits; however, we did not find that immature animals had proportionately thicker airway walls internal to the ASM. Our observation that the proportional inner wall increases with increasing generation is similar to results reported for other species (12, 24, 25). Ti can greatly amplify the degree of airway narrowing and may be a mechanism for heightened airway reactivity in patients with asthma and chronic obstructive pulmonary disease (28, 42). However, in our study, the absence of differences in Ai relative to airway size between mature and immature rabbits and a tendency for the mature to have greater values suggests that wall thickness does not account for the greater airway narrowing in immature than mature rabbits. However, in a previous study, our laboratory found that immature rabbits had proportionately thicker airway walls (31) after bronchoconstriction. It is therefore possible that other factors, such as airway wall edema produced during bronchoconstriction, may result in greater increases in Ti and thus greater airway narrowing in the immature animal. This mechanism would be consistent with the report of greater airway wall leak in immature than mature guinea pigs after intravenous histamine (2).Number of Alveolar Attachments
The immature rabbit airways had fewer alveolar attachments than mature rabbit airways of similar size. In addition, the number of attachments increased with increasing airway size for both age groups. This latter finding is consistent with a study in dogs (25), as well as a study in humans (30). We are not aware of any previous reports regarding changes in the number of alveolar attachments with lung growth and maturation. However, as the lung undergoes alveolarization early in life, one would expect that the number of attachments to the airways might increase with lung growth. In fact, rats and mice have mostly saccules and not alveoli at birth and fairly rapid alveolarization very early in the postnatal period (1, 38). Rabbits and humans are born with a small number of alveoli that increase in size and number during lung growth (36, 37). Physiological studies and computational models of airway narrowing have highlighted the importance of the forces of interdependence between the airways and the surrounding lung parenchyma in limiting airway narrowing (7, 10, 14, 40). In addition to the elastic load from the pulmonary recoil pressure of the lung parenchyma, there is an additional elastic load caused by local distortion of the lung parenchyma surrounding the airway as the ASM shortens and the airway narrows (3). This local distortion can be quantified in terms of a shear modulus. In a recent study in rabbits, our laboratory found a lower shear modulus in immature than mature rabbit lungs (35). The magnitude of the lower shear modulus in the immature rabbit is similar to the ~15% fewer alveolar attachments for immature compared with mature rabbit lungs.Structure-Function Relationships
We attempted to evaluate the effects of our observed maturational differences in airway structure on airway narrowing by using simple computational models that have been proposed in the literature (17, 22). The effect of an increased proportion of ASM was assessed using the model proposed by Moreno et al. (22) in 1986. The predicted maximal fold increase in resistance during bronchoconstriction was l.5-fold greater for the immature than the mature animal for generation 4 and almost 2-fold greater for generation 7, using the values of percent smooth muscle and PWAi obtained in our present study. Assuming that the differences in fraction of cartilage translate into comparable differences in airway compliance, we estimated the effect of less cartilage using a model proposed by Macklem (17). For a more compliant airway, there is a decrease in the load against muscle shortening, thus increasing the tension generated during narrowing. Simulations were performed for a 2-mm-diameter segment and another identically sized segment that is 30% more compliant, which approximates the average percent difference in cartilage for the immature and mature airways. Results show an almost twofold greater fractional airway narrowing in the more compliant airway, which corresponds to the immature airway. We then assumed that the previously observed lower shear modulus in the immature rabbit lung (35) is related to the lower number of alveolar attachments in the immature animal and applied Macklem's model to estimate airway narrowing in a single airway. The 15% lower shear modulus resulted in only a very small increase in airway narrowing.Thus, using simple models of airway narrowing, with each effect assessed independently, it appears that the relatively greater amount of smooth muscle and lesser amount of cartilage may contribute significantly to greater maximal airway narrowing seen in the immature rabbit lung. In contrast, the number of alveolar attachments and the proportional inner wall area may not be significant in contributing to maturational differences in maximal airway narrowing.
In conclusion, we found that immature rabbits have proportionately more muscle, less cartilage, and fewer alveolar attachments to the airway wall compared with mature rabbits. We conclude that these structural differences in the airway wall may contribute to the greater maximal airway narrowing observed in immature rabbits during bronchoconstriction.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: R. S. Tepper, James Whitcomb Riley Hospital for Children, Section of Pediatric Pulmonology, Rm. 2750, 702 Barnhill Dr., Indianapolis, IN 46202 (E-mail rtepper{at}iupui.edu).
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.
Received 10 November 1999; accepted in final form 1 June 2000.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Amy, RWM,
Bowes D,
Burri PH,
Haines J,
and
Thurlbeck WM.
Post natal growth of the mouse lung.
J Anat
124:
131-151,
1977[ISI][Medline].
2.
Arakawa, H,
Tokuyama K,
Yokoyama T,
Mochizuki H,
Morikawa A,
Kuroume T,
and
Barnes P.
Effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage in guinea pig airways.
Eur J Pharmacol
215:
51-56,
1992[ISI][Medline].
3.
Bellofiore, S,
Eidelman DH,
Macklem PT,
and
Martin JG.
Effects of elastase-induced emphysema on airway responsiveness to methacholine in rats.
J Appl Physiol
66:
606-612,
1989
4.
Bhutani, VK,
Rubenstein SD,
and
Shaffer TH.
Pressure-volume relationships of trachea in fetal newborn and adult rabbits.
Respir Physiol
43:
221-231,
1981[ISI][Medline].
5.
Croteau, JR,
and
Cook CD.
Volume-pressure and length-tension measurements in human tracheal and bronchial segments.
J Appl Physiol
16:
170-172,
1961
6.
Deoras, KS,
Wolfson MR,
Searls RL,
Hilfer SR,
and
Shaffer TH.
Developmental changes in tracheal structure.
Pediatr Res
30:
170-175,
1991[ISI][Medline].
7.
Ding, DJ,
Martin JG,
and
Macklem PT.
Effects of lung volume on maximal methacholine induced bronchoconstriction in normal humans.
J Appl Physiol
62:
1324-1330,
1987
8.
Gauthier, SP,
Wolfson MR,
Deoras KS,
and
Shaffer TH.
Structure-function of airway generations 0 to 4 in the preterm lamb.
Pediatr Res
31:
157-162,
1992[ISI][Medline].
9.
Gunst, SJ,
and
Lai-Fook SJ.
Effect of inflation on trachealis muscle tone in canine tracheal segments in vitro.
J Appl Physiol
54:
906-913,
1983
10.
Gunst, SJ,
Warner DO,
Wilson TA,
and
Hyatt RE.
Parenchymal interdependence and airway response to methacholine in excised dog lobes.
J Appl Physiol
65:
2490-2497,
1988
11.
Hislop, AA,
and
Haworth SG.
Airway size and structure in the normal fetal infant lung and the effect of premature delivery and artificial ventilation.
Am Rev Respir Dis
140:
1717-1726,
1989[ISI][Medline].
12.
James, AL,
Paré PD,
and
Hogg JC.
The mechanics of airway narrowing in asthma.
Am Rev Respir Dis
139:
242-246,
1989[ISI][Medline].
13.
Lambert, RK,
and
Paré PD.
Lung parenchymal shear modulus of mature and immature rabbit lungs.
J Appl Physiol
83:
140-147,
1997
14.
Lambert, RK,
and
Paré PD.
Lung parenchymal shear modulus, airway wall remodeling, and bronchial hyperresponsiveness.
J Appl Physiol
83:
140-147,
1997.
15.
Lambert, RK,
Wiggs BR,
Kuwano K,
Hogg PC,
and
Paré PD.
Functional significance of increased airway smooth muscle in asthma and COPD.
J Appl Physiol
74:
2771-2781,
1993
16.
Littell, RC,
Milliken G,
Stroup W,
and
Wolfinger R.
SAS system for mixed models.
In: AnonymousCary NC: SAS Institute, 1996, p. 87-134.
17.
Macklem, PT.
A theoretical analysis of the effect of airway smooth muscle load on airway narrowing.
Am J Respir Crit Care Med
153:
83-89,
1996[Abstract].
18.
Martin, JG,
Opazo-Saez A,
Du T,
Tepper RS,
and
Eidelman DH.
In vivo airway reactivity: predictive value of morphological estimates of airway smooth muscle.
Can J Physiol Pharmacol
70:
597-601,
1992[ISI][Medline].
19.
Matsuba, K,
and
Thurlbeck WM.
A morphometric study of bronchial and bronchiolar walls in children.
Am Rev Respir Dis
105:
908-913,
1972[ISI][Medline].
20.
McFawn, PK,
and
Mitchell HW.
Bronchial compliance and wall structure during development of the immature human and pig lung.
Eur Respir J
10:
27-34,
1997[Abstract].
21.
Moreno, RH,
McCormack GS,
and
Mullen BM.
Effect of intravenous papain on tracheal pressure-volume curves in rabbits.
J Appl Physiol
60:
247-252,
1986
22.
Moreno, RH,
Hogg JC,
and
Paré PD.
Mechanics of airway narrowing.
Am Rev Respir Dis
133:
1171-1180,
1986[ISI][Medline].
23.
Murphy, TM,
Mitchell RW,
Halayko A,
Roach J,
Roy L,
Kelly EA,
Munoz NM,
Stephens NL,
and
Leff AR.
Effect of maturational changes in myosin content and morphometry on airway smooth muscle contraction.
Am J Physiol Lung Cell Mol Physiol
260:
L471-L480,
1991
24.
Okazawa, M,
Muller N,
McNamara AE,
Child S,
Verburgt L,
and
Paré PD.
Human airway narrowing measured using high resolution computed tomography.
Am J Respir Crit Care Med
154:
1557-1562,
1996[Abstract].
25.
Okazawa, M,
Vedal S,
Verburgt L,
Lambert RK,
and
Paré PD.
Determinants of airway smooth muscle shortening in excised canine lobes.
J Appl Physiol
78:
608-614,
1995
26.
Olsen, CR,
Sevens AE,
Pride NB,
and
Staub NC.
Structual basis for decreased compressibility of tracheae and bronchi.
J Appl Physiol
23:
35-39,
1967
27.
Panitch, HB,
Deoras KS,
Wolfson MR,
and
Shaffer TH.
Maturational changes in airway smooth muscle structure-function relationships.
Pediatr Res
31:
151-156,
1992[ISI][Medline].
28.
Paré, PD,
Bai TR,
and
Robert CR.
The structural and functional consequences of chronic allergic inflammation of the airways.
In: The Rising Trends in Asthma, edited by Chadwick DJ,
and Chichester GC.. New York: Wiley, 1997, p. 71-89. Ciba Foundation Symposium 206.
29.
Penn, RB,
Wolfson MR,
and
Shaffer TH.
Developmental differences in tracheal cartilage mechanics.
Pediatr Res
26:
429-433,
1989[ISI][Medline].
30.
Petty, TL,
Silvers WG,
and
Stanford RE.
Radial traction and small airways disease in excised human lungs.
Am Rev Respir Dis
133:
132-135,
1986[ISI][Medline].
31.
Shen, X,
Bhargava V,
Wodicka GR,
Doerschuk CM,
Gunst SJ,
and
Tepper RS.
Greater airway narrowing in immature than in mature rabbits during methacholine challenge.
J Appl Physiol
81:
2637-2643,
1996
32.
Sward-Comunelli, SL,
Mabry SM,
Truog WE,
and
Thibeault DW.
Airway muscle in preterm infants: changes during development.
J Pediatr
130:
570-576,
1997[ISI][Medline].
33.
Tepper, RS,
Shen X,
Bakan E,
and
Gunst SJ.
Maximal airway response in mature and immature rabbits during tidal ventilation.
J Appl Physiol
79:
1190-1198,
1995
34.
Tepper, RS,
Shen X,
Marx K,
and
Gunst SJ.
Effect of PEEP on the response of pulmonary resistance to methacholine: comparison of mature and immature rabbits (Abstract).
Eur Respir J
8:
208s,
1995.
35.
Tepper, RS,
Wiggs B,
Gunst SJ,
and
Paré PD.
Comparison of the shear modulus of mature and immature rabbit lungs.
J Appl Physiol
87:
711-714,
1999
36.
Thurlbeck, WM.
Lung growth and alveolar multiplication.
Pathobiology
5:
1-34,
1975.
37.
Thurlbeck, WM.
Post natal growth and development of the lung.
Am Rev Respir Dis
111:
803-844,
1975[ISI][Medline].
38.
Thurlbeck, WM,
and
Wang NS.
Structure of the lung.
In: Respiratory Physiology, edited by Widdicombe JG.. Baltimore, MD: University Park, 1970, p. 1-30.
39.
Von Hayek, H.
The structure of the bronchial wall.
In: The Human Lung. New York: Hafner, 1960, p. 139-161.
40.
Warner, DO,
and
Gunst SJ.
Limitation of maximal bronchoconstriction in dogs.
Am Rev Respir Dis
145:
553-560,
1992[ISI][Medline].
41.
Weibel, ER.
The point counting method.
In: Morphometry of The Human Lung. New York: Academic, 1963, p. 19-21.
42.
Wiggs, BR,
Bosken C,
Paré PD,
James A,
and
Hogg JC.
A model of airway narrowning in asthma and in chronic obstructive pulmonary disease.
Am Rev Respir Dis
145:
1251-1258,
1992[ISI][Medline].
43.
Wiggs, BR,
Moreno R,
Hogg JC,
Hilliam C,
and
Paré PD.
A model of the mechanics of airway narrowing.
J Appl Physiol
69:
849-860,
1990
This article has been cited by other articles:
|
|
 |
|
  Z. Xue, L. Zhang, Y. Liu, S. J. Gunst, and R. S. Tepper Chronic inflation of ferret lungs with CPAP reduces airway smooth muscle contractility in vivo and in vitro J Appl Physiol, March 1, 2008; 104(3): 610 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bayat, L. Porra, H. Suhonen, C. Nemoz, P. Suortti, and A. R. A. Sovijarvi Differences in the time course of proximal and distal airway response to inhaled histamine studied by synchrotron radiation CT J Appl Physiol, June 1, 2006; 100(6): 1964 - 1973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Henschen, J. Stocks, I. Brookes, and U. Frey New aspects of airway mechanics in pre-term infants Eur. Respir. J., May 1, 2006; 27(5): 913 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Tepper, R. Ramchandani, E. Argay, L. Zhang, Z. Xue, Y. Liu, and S. J. Gunst Chronic strain alters the passive and contractile properties of rabbit airways J Appl Physiol, May 1, 2005; 98(5): 1949 - 1954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kovar, K. E. Willet, A. Hislop, and P. D. Sly Impact of postnatal glucocorticoids on early lung development J Appl Physiol, March 1, 2005; 98(3): 881 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ramchandani, X. Shen, S. J. Gunst, and R. S. Tepper Comparison of elastic properties and contractile responses of isolated airway segments from mature and immature rabbits J Appl Physiol, July 1, 2003; 95(1): 265 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Lambert, R. Ramchandani, X. Shen, S. J. Gunst, and R. S. Tepper Computational model of airway narrowing: mature vs. immature rabbit J Appl Physiol, August 1, 2002; 93(2): 611 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kovar, P. D. Sly, and K. E. Willet Postnatal alveolar development of the rabbit J Appl Physiol, August 1, 2002; 93(2): 629 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. DUGUET, C.-G. WANG, R. GOMES, H. GHEZZO, D. H. EIDELMAN, and R. S. TEPPER Greater Velocity and Magnitude of Airway Narrowing in Immature Than in Mature Rabbit Lung Explants Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1728 - 1733. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
) and
mature (
) rabbits. Values are means ± SE.
Di decreases with increase in generation number
and is significantly larger for mature rabbits (P < 0.05). B: Ti vs. generation for
immature (
