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1 Department of Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75390-9034; and 2 Departments of Medicine and Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 99195
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Pneumonectomy (PNX)
leads to chronic asymmetric ventilatory loading of respiratory muscles
(RM). We measured RM energy requirements during exercise from RM blood
flow (
) using a fluorescent microsphere technique in dogs that
had undergone right PNX as adults (adult R-PNX) or as puppies (puppy
R-PNX), compared with dogs subjected to right thoracotomy without PNX
as puppies (Sham) and to left PNX as adults (adult L-PNX). Ventilatory
work (
) was measured during exercise. RM weight was determined
post mortem. After adult and puppy R-PNX, the right hemidiaphragm
becomes grossly distorted, but and right costal muscle mass
increased only after adult R-PNX. After adult L-PNX, the diaphragm was
undistorted; and left hemidiaphragm RM were
elevated, but muscle mass did not increase. Mass of parasternal muscle
did not increase after adult R-PNX, despite increased . Thus
muscle mass increased only in response to the combination of chronic
stretch and dynamic loading. There was a dorsal-to-ventral gradient of
increasing within the diaphragm, but the distribution was
unaffected by anatomic distortion, hypertrophy, or workload, suggesting
a fixed pattern of neural activation. The diaphragm and parasternals
were the primary muscles compensating for the asymmetric loading from PNX.
pneumonectomy; diaphragm; microspheres; work of breathing; dog
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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CHANGES IN
DISTRIBUTION of blood flow () among respiratory muscles
(RM) in response to ventilatory loading provides a sensitive index of
compensatory muscle recruitment (25). Our laboratory previously showed, in adult dogs after left pneumonectomy (L-PNX; 45%
lung resection) (16), that diaphragmatic perfusion
during heavy exercise constitutes ~23% of total RM and 40% of total
inspiratory muscle oxygen delivery, with the costal diaphragm receiving
a higher than the crural diaphragm. However, in that study
(16), control measurements were not available, and
to the left and right sides was not compared. In addition, key anatomic
differences exist after L-PNX and right pneumonectomy (R-PNX) in the
dog. After L-PNX, configuration of the thorax and diaphragm is altered very little because the cardiac lobe of the right lung herniates across
the midline below the heart, reconstituting the cardiac fossa and
maintaining separation of the heart and diaphragm (14) (Fig. 1). In contrast, after R-PNX (55%
lung resection), the cardiac lobe is no longer present, and the right
hemidiaphragm becomes elevated and pulled to the right, leading to an
asymmetric configuration of the diaphragm (Fig. 1). Ventilatory power
requirements or work () increased more significantly after R-PNX
than after L-PNX, due to the greater loss of lung units and airway
cross-sectional area (13); the increase is greater when
R-PNX is performed as an adult than as an immature animal
(32). Thoracic distortion in adult dogs after R-PNX and
the increase in are associated with an increase of muscle mass
and total mitochondrial volume of the right hemidiaphragm compared with
the left (13).
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Information is not available on the distribution of neural
activation and RM blood flow (RM) in normal dogs
during treadmill exercise or on how this distribution may alter because
of asymmetrical distortion of the thorax. Skeletal muscle
hypertrophy can be induced by stretch even when the muscle is
denervated, resulting in increased fiber length and cross-sectional
area (1, 29). High-resistance exercises, such as
weightlifting or heavy manual labor, can induce muscle hypertrophy,
primarily by increasing muscle fiber cross-sectional area (3,
26). Asymmetrical diaphragmatic distortion after R-PNX might
have induced hypertrophy by 1) asymmetrical stretch of the
diaphragm, independent of added work requirements and/or 2)
regional increases in .
Our hypotheses are as follows: after PNX, 1) asymmetrical
recruitment and hypertrophy of RM will occur in response to a chronic asymmetrical ventilatory load; 2) the pattern of regional
recruitment in the diaphragm will become less uniform in response to
asymmetrical loading and distortion; 3) stretch is the
primary mechanism inducing asymmetrical hypertrophy; and 4)
changes in RM distribution will vary depending on
whether PNX is right or left and whether it is performed on an immature
animal or on an adult. To test these hypotheses, measurements were made
in three groups of foxhounds more than a year after 1) R-PNX
performed on adult dogs (adult R-PNX), 2) R-PNX performed on
puppies (puppy R-PNX), and 3) right thoracotomy without
resection performed on puppies (Sham). In addition, our laboratory has
already reported distribution of measured by radioactive
microsphere technique more than a year after L-PNX on adult dogs (adult
L-PNX). Thus it is possible to compare RM
distribution with distribution of RM mass and with the pattern of
thoracic distortion in all four groups.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Animal Surgery
The experimental protocol was approved by the Institutional Review Board for Animal Research. Male purebred foxhounds were obtained from commercial breeders and studied after undergoing thoracic surgery as follows: 1) R-PNX) performed on puppies at 2 mo of age (n = 3) or on fully mature adults at 1 yr of age (n = 3) or 2) right thoracotomy without PNX (Sham) performed at 2 mo of age (n = 6). The surgical procedure has been described in detail previously (11, 33). In all dogs, exercise studies were performed ~1 yr after surgery. A customized, leak-free respiratory mask was constructed for each dog to allow ventilatory measurements to be made during exercise (2). Bilateral carotid artery loops were constructed to allow acute catheterization of the artery and the left ventricle. All dogs were trained to run freely on a motorized treadmill by methods described elsewhere (12).Respiratory Apparatus
Animals breathed through large, one-way respiratory valves (no. 2700, Hans-Rudolph, Kansas City, MO). The inspiratory port was connected to a screen pneumotachometer (no. 3813, Hans-Rudolph). The expiratory port was connected to a mixing chamber and a heated screen pneumotachometer. Expired gas concentrations were sampled continuously from the distal end of the mixing chamber by a mass spectrometer (MGA-1100, Perkins-Elmer). The pneumotachometer-computer system was calibrated by the method of Yeh et al. (36). Flow signals were integrated to obtain volume expressed in BTPS conditions. O2 uptake and CO2 production were calculated from mixed expired gas concentrations.Measurement of
Pes), the tidal volume, and the area of the Pes-tidal volume loop not recovered from the stored lung elastic recoil, as described previously (13, 16). Transpulmonary pressure was defined
as the difference between Pes and mouth pressure. All signals were digitized by computer at 50 Hz and were averaged over a predetermined number of breaths.
Measurement of RM
RM. Under local anesthesia, a Gensini
catheter was inserted, in a retrograde fashion, via a carotid artery
loop into the left ventricle. Position of the catheter was checked by
continuous pressure monitoring using a Statham transducer connected to
a Hewlett-Packard carrier amplifier. An intravenous catheter (Cook, Bloomington, IN) was inserted via the other carotid artery loop into
the aorta to record systemic arterial pressure. Catheters were flushed
with heparinized saline and sutured to the skin. A fluid-filled
reference catheter was sutured to the dog's lateral chest at the
midpoint along the anteroposterior diameter. Vascular pressures were
recorded continuously and were averaged by computer over a
predetermined number of heartbeats.
Baseline ventilatory and hemodynamic data were collected while the animal stood quietly on a treadmill wearing the respiratory attachments. Treadmill exercise was then performed at preselected workloads (6 mph, 0% grade; 8 mph, 5% grade; and 8 mph, 15% grade). Workloads were separated by a rest period of 30-60 min. When steady-state conditions were reached at each workload, usually by the end of the third minute, ~3 × 106 fluorescent microspheres (15-µm diameter; crimson, yellow-green, orange, or blue-green; Molecular Probes, Eugene, OR) were injected as rapidly as possible into the left ventricle. Each microsphere suspension was dispersed in an ultrasonic water bath for 10 min and vortexed just before injection. Each injection was followed by three saline flushes to clear the dead space of the catheter, and the stopcock was changed after each injection. Reference blood samples were withdrawn from the other carotid artery into a heparinized glass syringe at a constant rate for 2 min, beginning just before each microsphere injection. Reference blood was transferred into labeled vials, and the lines and syringes were rinsed with 2% Tween 80 to ensure recovery of all microspheres.
Postmortem Studies
After completion of physiological studies, animals were euthanized by an overdose of pentobarbital sodium. Major RM, kidneys, gastrocnemius muscles, and the ventricles were dissected completely, trimmed of extraneous tissue, and weighed on a Mettler electrobalance. Each costal hemidiaphragm was divided into eight regions, and each crural hemidiaphragm was divided into five regions (Fig. 2). Aliquots of tissue were taken from each region or muscle, weighed, digested with potassium hydroxide in Tween 80, and filtered. Microspheres were recovered by negative pressure filtration and dissolved in 2-(2-ethoxyethoxy) ethyl acetate; the fluorescence was measured after dissolution (LS-50, Perkin-Elmer). Reference blood samples were processed similarly. At least 1,000 microspheres were recovered in each tissue sample, with the exception of the posterior cricoarytenoid. to each
sample i (i in ml/min) was
calculated as i = (fli/fref) × R, where
fli is the fluorescence of sample i,
flref is the fluorescence of the reference blood sample,
and R is the withdrawal rate (ml/min) of the reference blood sample.
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Statistical Comparison
Data from several previous studies have been included in the statistical comparisons. Three foxhounds are included in which RM weights and muscle were measured in a previous study; was measured by the radioactive microsphere technique more than a year
after adult L-PNX had been performed (16). RM weights have
been included from five foxhounds after adult R-PNX and five Sham dogs;
in these two groups, was measured at rest and exercise, and
muscle morphometry was studied (13). Seven additional
adult R-PNX dogs that were part of an unpublished study have also been included.
Because RM mass in humans and dogs are closely related to body
weight, specific muscle weight was expressed as grams per kilogram of
body weight (3, 21). Specific regional was
expressed as milliliters per minute per gram of muscle weight. Data are shown as means ± SE. was expressed as kilogram-meters per
minute per kilogram of body weight. , with respect to
ventilation, was fit to the Otis model (23) of
and mechanical properties of the lung and compared by
repeated-measures ANOVA at discrete intervals of ventilation. Regional
diaphragmatic was also compared by repeated-measures ANOVA.
RM was analyzed with respect to gastrocnemius
by linear regression analysis and compared among groups by
ANCOVA. This comparison eliminates potential errors due to variability
in the reference blood sample. Post hoc testing was performed using
Fisher's multiple comparison and the Bonferroni correction among three
groups. P < 0.0167 was considered significant. Asymmetry between right and left costal, crural, and hemidiaphragm muscle weights, specific , and per organ were analyzed
by the nonparametric Wilcoxon signed-rank test in adult R-PNX, puppy R-PNX, adult L-PNX, and Sham groups. P < 0.0125 was
considered significant.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Muscle Mass and Ventilatory Power Output
Peak oxygen uptake, ventilation,, and systemic arterial
pressure during exercise are shown in Table
1. At a given ventilation, total RM power
output to overcome resistance of the lungs and apparatus was
significantly higher in PNX than in Sham animals, and higher in adult
PNX dogs than in puppies (Fig. 3). Muscle weights for the four groups of dogs are given in Table
2. Significant increases in muscle mass
per kilogram of body weight were seen only in the adult R-PNX group and
only in the diaphragm. Muscle mass of the right and left hemidiaphragm
in the adult R-PNX group was significantly larger than in the Sham and
adult L-PNX groups.
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Regional Distribution of Diaphragmatic
among the different regions of
costal and crural diaphragm is shown at rest and peak exercise in Fig.
4. Specific was not significantly
different between the right and left hemidiaphragm; hence, results from
the right and left costal diaphragm and from the right and left crural
diaphragm have been averaged for comparison among groups. Only three
groups are compared. Regional in the diaphragm was not measured
in the adult L-PNX group. In Sham animals at rest and exercise, there was a significant steep rise in regional specific from the most
dorsal regions to a peak in the midcostal region, beyond which
either plateaus or declines slightly toward the midsternal region. The
pattern is similar to that reported by Brancatisano et al.
(5) in anesthetized animals and remains fixed from rest to
heavy exercise. The only difference between our results and those of
Brancatisano et al. (5) was that we saw a similar gradient
in the crural diaphragm. Despite asymmetric distortion of the diaphragm
after PNX, the dorsal-to-ventral gradient per gram of costal
muscle remained unaffected. Although absolute is significantly
greater to the hypertrophied right costal diaphragm than to the left
hemidiaphragm after adult R-PNX, specific remains normal, and
its pattern of distribution remains normal. Regional and total
to the costal diaphragm is significantly greater after adult R-PNX than
in other groups, which is consistent with a greater fraction of the
total RM being diverted to the diaphragm after adult
R-PNX. Thus the pattern of distribution to the costal diaphragm
is unaffected by diaphragm distortion after adult or puppy R-PNX (Fig.
4); this suggests that the pattern of neural activation is unaffected
as well. The normal gradient is lost in the dorsal part of the
hypertrophied crural diaphragm after adult R-PNX.
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to RM Groups
rose at a significantly steeper slope
(P < 0.01) with respect to gastrocnemius than
that in the Sham and puppy R-PNX groups during exercise (Fig.
5). In the adult R-PNX group, total
to parasternal muscles was significantly elevated with respect
to that in the Sham and puppy R-PNX (P = 0.002).
Similarly, in the adult R-PNX group, total to the external and
internal intercostals rose at a steeper slope with respect to
gastrocnemius blood than that in the Sham and puppy R-PNX groups
(P < 0.001; Fig. 6). The
steeper slope of the increase in triangularis compared with
gastrocnemius in the adult R-PNX group was of borderline
significance (P = 0.03). The posterior cricoarytenoid muscle (PCA), which spreads the vocal cords and reduces laryngeal resistance during inspiration, is also considered to be an inspiratory muscle; specific PCA increases during exercise at a rate
similar to that of the diaphragm. In the adult R-PNX group, to
the PCA rises at a significantly steeper slope than that in either the
Sham or puppy R-PNX group in accordance with the rise in diaphragmatic (Fig. 7). The slopes of increase
in total to both inspiratory and expiratory muscles are
significantly steeper in the adult R-PNX group than that shown in both
of the other two groups, in accordance with the higher
after R-PNX in adults (Fig. 8).
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Relative RM, expressed as a percentage of
the total, is shown in Table 3; there was
no change in this pattern from rest to exercise. Relative to
the costal diaphragm was approximately twice that to the crural
diaphragm. Overall, the normal diaphragm received almost 40% of total
inspiratory and 30% of total RM. Relative
diaphragmatic with respect to total RM was
not altered in the puppy R-PNX group (42.8 and 30.2% respectively) but
was significantly higher in the adult R-PNX group (49.3 and
39.4%, respectively), mainly due to a higher flow to the costal
diaphragm. In adult R-PNX, a significantly greater percentage of the
total RM and RM oxygen delivery went to the
inspiratory muscles than that shown in the puppy R-PNX or Sham groups
(80 vs. 70 and 72% respectively, P < 0.0167).
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Asymmetry Between the Right and Left Hemidiaphragm
In Sham animals, muscle mass and total in the right crural
diaphragm were greater than in the left, and this pattern was not
changed by R-PNX (Table 4). In the adult
R-PNX group, the entire right hemidiaphragm (costal and crural) was
hypertrophic compared with the left side and entrained a significantly
greater flow than the left. Total to the right hemidiaphragm
was significantly greater than that to the left in the puppy R-PNX
group, although muscle mass was not significantly different between the
two sides. Data suggest that the energy requirements of the right
hemidiaphragm are significantly increased in both adult and puppy R-PNX
groups. Muscle mass of the right costal and right hemidiaphragm in the puppy R-PNX group was between those in the Sham and adult R-PNX groups
but was not significantly different from either. An unexpected finding,
in the adult L-PNX dogs, was an increase in total and specific
to the left costal and crural diaphragms, suggesting a greater energy
requirement by the left hemidiaphragm during exercise, without evidence
of compensatory hypertrophy. Specific per gram of muscle was
uniformly partitioned between the right and left hemidiaphragm in the
other groups. The data suggest that, in the adult R-PNX animals,
hypertrophy of the right hemidiaphragm just balanced the increased
energy requirements of the right hemidiaphragm, thus keeping the energy
requirements per gram of muscle the same.
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to Other Organs
to the gastrocnemius muscles agree well
with that previously reported by Musch et al. (22) in
trained foxhounds. Specific and total to the left ventricle
increased during exercise at a steeper slope, with respect to load,
than any skeletal muscles studied and did not differ significantly among groups, although the data were variable (Fig.
9). Total and specific to the
right ventricle during exercise were significantly higher in the adult
R-PNX group compared with the Sham or puppy R-PNX groups (Fig. 9),
which is consistent with greater right ventricular afterload in the
former. to the kidneys did not differ with respect to exercise
intensity or experimental group.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Major Findings
distribution within the diaphragm.
In Sham animals at rest and during exercise, there was a
dorsal-to-ventral gradient of increasing per gram of muscle
(specific ) in the costal diaphragm at rest and exercise,
similar to that reported by Brancatisano et al. (5) in
resting dogs (Fig. 4). rose steeply from dorsal to the
midcostal region, beyond which it either reached a plateau or declined
toward the midsternal region. The decline was most evident at rest and
tended toward a plateau as increased. A similar
dorsal-to-ventral rise in specific occurred in the crural
diaphragm. Despite distortion and hypertrophy of the diaphragm and a
high ventilatory load after adult R-PNX, this pattern persisted in the
costal diaphragm; however, in the hypertrophied diaphragm after adult
R-PNX, the gradient was lost in the most dorsal region of the crural diaphragm.
Distortion of the diaphragm.
In the adult R-PNX group, was significantly elevated with
respect to that in the Sham and puppy R-PNX groups, and the right hemidiaphragm was elevated and displaced to the right, adjacent to the
base of the heart (Fig. 1 and Table 4). Total to the elevated
right hemidiaphragm in the adult R-PNX group was significantly elevated
compared with the left. in the puppy R-PNX group was significantly less than in the adult R-PNX group, although elevation and displacement of the right hemidiaphragm were the same. Puppy R-PNX
right costal muscle mass and were intermediate between those in
the Sham and adult R-PNX groups, which is consistent with an increased
contribution to the work of breathing from the elevated right
hemidiaphragm, but increases were not statistically significant. In
adult L-PNX dogs, the left hemidiaphragm remained separated from the
heart by the cardiac lobe of the right lung (Fig. 1); hence, the left
hemidiaphragm was relatively less distorted. On the other hand, total
was significantly elevated in the left hemidiaphragm at rest
and exercise (P < 0.001), consistent with the
chronically elevated power requirements of the left hemidiaphragm.
Compensatory mechanisms.
Compensation for the increased RM loading by PNX was asymmetrical; it
occurred by either regional increases in muscle mass, specific ,
or both. Assuming that the distribution of reflects the
distribution of dynamic work requirements of muscle, primary compensation for the increased after adult R-PNX was derived from increased contributions from the diaphragm and parasternal muscles. Increased dynamic work requirements alone did not induce significant hypertrophy of RM. Hypertrophy occurred only in the diaphragm and only after adult R-PNX, in which the right hemidiaphragm was both passively stretched and dynamically loaded. Hypertrophy was
significantly greater on the right side, which also received 17% more
than the left side, suggesting a correspondingly greater work
requirement of the right hemidiaphragm. Significant diaphragm hypertrophy did not occur in puppy R-PNX dogs, in which distortion of
the diaphragm was similar to that in the adult R-PNX group, but power
requirements were not signifiantly increased above Sham controls.
Hypertrophy did not occur in the left hemidiaphragm after L-PNX. Power
requirements were increased to an intermediate level, and
requirements of the left hemidiaphragm were 20% higher than on the
right, but distortion of the diaphragm was minimal. Thus significant RM
hypertrophy occurred only when there was a combination of increased
muscle stretch and increased dynamic work requirements.
Regional Distribution of in the Diaphragm
is not uniformly distributed in the costal or crural
diaphragm; it follows a distinct pattern that probably reflects the pattern of neural activation. There have been no previous studies on
how anatomic distortion affects the pattern of blood flow distribution or of neural activation. The dorsal-to-ventral gradient, as measured by
Brancatisano et al. (5) in the costal diaphragm of
anesthetized dogs, was unchanged by position or by an inspiratory
resistive load, which raised by ~30%. In our adult R-PNX
animals, to the diaphragm during exercise increased by six- to
sevenfold above that at rest. Diaphragmatic distortion, increased
ventilatory loading, and hypertrophy did not alter this pattern of
specific in the costal diaphragm. Even when the
right costal diaphragm hypertrophied with a high total
, specific costal was the same on each
side, suggesting that neural activation on the two sides was the same.
This pattern of distribution appears to be topographically
stable, regardless of either anatomic distortion or ventilatory
loading, as if the pattern of neural activation were fixed. This would
imply that the right and left costal diaphragms are activated as a unit
and that a significantly greater fraction of the total is
subserved by the ventral costal diaphragm as is progressively increased.
Distribution in Diaphragms of Other Species
distribution have
been reported. Manohar (19, 20) found a higher in
the costal than crural diaphragm in ponies during exercise similar to
that in dogs. However, Soust et al. (30) reported a lower
to the costal than crural diaphragm in resting conscious sheep;
measurements were not obtained during exercise. Sexton and Poole
(27, 28) also found a different pattern of
distribution in the costal diaphragm of rats and hamsters. In rats and
hamsters at rest and during treadmill exercise, was
significantly lower to the ventral costal diaphragm than to the medial
or dorsal costal regions, an opposite direction of gradient
from that seen in dogs. Exercise training did not alter the magnitude
or distribution of diaphragmatic . Reasons for the differences
among species are unclear but may relate to the size and shape of the
diaphragm, weight of abdominal contents, the pattern of running, and,
ultimately, the central pattern for neural activation.
Patterns of Mechanical Advantage and Innervation in Dog Diaphragms
In addition to the dorsal-to-ventral distribution of increasing in the diaphragm, there is a dorsal-to-ventral gradient of
increasing mechanical advantage (34, 35) and a similar dorsal-to-ventral pattern of segmental motor innervation of the diaphragm (7). The sixth cervical root of the phrenic
nerve predominantly activates the crural and dorsal costal diaphragm, and the fifth cervical root predominantly activates the ventral and
sternal portions of the costal diaphragm. The consistent pattern in
regional distribution, mechanical advantage, and innervation of
the diaphragm suggests that muscle activation may preferentially distribute power and specific to those regions with a higher mechanical advantage. Thus specific , although distributed
nonuniformly with respect to muscle mass, may be uniformly distributed
with respect to mechanical advantage and O2 requirements.
Types of Muscle Hypertrophy
Hypertrophy of the diaphragm, acting as a pump, may be analogous to that which occurs in the heart pump. Systemic hypertension and weightlifting cause the left ventricle to undergo "concentric" hypertrophy, in which the ventricular wall becomes abnormally thick with respect to ventricular volume (17). Concentric hypertrophy is associated with increased numbers of sarcomeres arranged in parallel. Compensation occurs by distributing the increased total force among more parallel contractile units, so that the force required from each unit is minimized, i.e., wall stress tends to be normalized (9). In endurance athletes or in patients with a regurgitant valve, the left ventricle undergoes "eccentric" hypertrophy, in which diastolic volume increases but the ratio of wall thickness to volume (17) remains normal. In eccentric hypertrophy, there are increased numbers of contractile units arranged in series. Thus, for a given fractional shortening of each sarcomere, there is a larger absolute decrease in circumference of the heart. Eccentric hypertrophy raises stroke volume and distributes the increased pressure-volume work among more contractile units. As far as we know, the RM is the only other skeletal muscle system in the body that might mimic the heart in this regard. Both the heart and the RM operate to change the volume of a distensible cavity and can operate from different end-diastolic or end-tidal volumes in response to a load. Weightlifters or manual laborers develop concentric hypertrophy of the diaphragm with thick walls with respect to chest circumference (3). The elevated right hemidiaphragm after R-PNX is an example of eccentric hypertrophy induced by stretch that is similar to that achieved artificially in the avian wing by Alway et al. (1). We do not know the stroke volume of the right hemidiaphragm, but it may indeed be enhanced, because adhesions do not occur after R-PNX in dogs, as they do in humans, thus leaving the diaphragm freely mobile. Furthermore, mechanical advantage, as defined by Wilson et al. (35), may be enhanced in the elevated right hemidiaphragm because pressure change during mouth occlusion may theoretically increase for a given fractional fiber length change.Lower after PNX in Puppies than After PNX in Adults
after PNX in dogs is mainly due to an increased elastic and viscous
resistance of lung tissue and airways (32). A greater
fraction of the increased work is inspiratory, so that, at very high
work loads, a greater fraction of the work is shifted to inspiratory
muscles. In puppy R-PNX animals, work of breathing was significantly
lower than in adult R-PNX dogs, owing to a lower viscous resistance of
airways. Airway flow resistance after PNX in growing dogs may be
minimized by airway dilatation or by growth of more airway segments,
both of which increase total airway cross-sectional area. Our
laboratory has already shown that alveolar regenerative growth is more
vigorous in pneumonectomized puppies (31), resulting in a
more nearly normal lung volume and elastic recoil than in dogs
pneumonectomized as adults. We also found higher number and volume of
respiratory bronchioles in pneumonectomized puppies compared with sham
animals, whereas bronchiole diameter remained unchanged
(15), consistent with regenerative growth of acinar
airways. Whether regenerative growth of conducting airways
occurs after pneumonectomy has not been rigorously assessed and cannot
be ruled out. Recent data from spiral computerized tomography scans
have suggested progressive enlargement of conducting airway
cross-sectional area and cumulative length in immature dogs after R-PNX
that was in excess of that in matched controls. The net result is a
lower conducting airway resistance than was expected with the amount of
lung removed (6). It is also possible that dilatation of
conducting airways occurs to a greater extent in dogs pneumonectomized
as puppies than as adults. The consequent reduction in flow resistance
could lower and explain the lower when PNX is performed
when the dog is a puppy rather than after maturation. The same may
occur in the arterial tree of dogs that underwent PNX as puppies, thus accounting for the lower pulmonary arterial pressure observed in dogs
that underwent PNX as puppies than as adults (32). This could also explain the lower right ventricular myocardial in the puppy R-PNX group compared with the adult R-PNX group in the present study (Fig. 9). These possibilities require further study.
Limits of RM
, with respect to
systemic arterial pressure during treadmill exercise, does not approach these maximum values (16). The present study's data from
dogs after R-PNX have been added to previous data and are shown in Fig.
10. Although is significantly
higher after the more extensive R-PNX (13), specific
diaphragmatic perfusion during exercise still does not approach that
seen during maximal vasodilatation. This analysis again supports the
conclusion that maximum perfusion to the diaphragm is not a major
factor in limiting exercise after PNX. However, at a given cardiac
output after PNX, a higher RM diverts oxygen
delivery away from locomotive muscles, which, in turn, aggravates
muscle acidosis and further increases ventilatory burden at a given
workload, ultimately contributing to exercise limitation
(10).
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In conclusion, we found a steep dorsal-to-ventral rise of per
gram of muscle in costal and crural diaphragms, similar to the
dorsal-to-ventral gradient in mechanical advantage within the
diaphragms of normal dogs, as reported by Wilson et al.
(35). As a matter of speculation, specific in the
diaphragm, although unevenly distributed with respect to muscle mass,
may be uniformly distributed with respect to regional mechanical
advantage and oxygen requirements. This perfusion pattern in the costal
diaphragm is not affected by asymmetric distortion of the diaphragm or
by ventilatory loading during exercise, which increase specific
diaphragmatic by six- to sevenfold, as if the pattern of neural
activation is fixed. A similar gradient was also present in the normal
crural diaphragm but was partially lost in the hypertrophied crural
diaphragm after adult R-PNX. In response to the chronically elevated
after PNX, RM compensation occurred by regional increases in
specific and muscle mass. The increased
after PNX were subserved primarily by the diaphragm and parasternal
muscles; however, all of the rib cage inspiratory and expiratory
muscles participated. Hypertrophy of the diaphragm occurred only in
response to a combination of increased dynamic work requirements and
chronic stretch of the diaphragm but did not occur in response to
either factor alone.
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ACKNOWLEDGEMENTS |
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We thank David Treakle, Stacey Arnold, and the staff of the Animal Resources Center for skillful technical assistance and excellent care of the animals.
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FOOTNOTES |
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This project was supported by National Heart, Lung, and Blood Institute Grants RO1-HL-45716, HL-40070, and HL-54060. S. Takeda was supported by the Will Rogers Memorial Foundation and Japan Ministry of Education. This work was done during the tenure of C. C. W. Hsia as an Established Investigator of the American Heart Association.
Current address for S. Takeda: Dept. of Surgery for Functional Regulation, Osaka Univ. Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Address for reprint requests and other correspondence: C. C. W. Hsia, Div. of Pulmonary and Critical Care Medicine, Dept. of 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.
Received 19 October 1999; accepted in final form 12 June 2000.
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ABSTRACT
INTRODUCTION
METHODS
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DISCUSSION
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