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Vol. 84, Issue 4, 1278-1288, April 1998
Departments of 1 Physiology and Biophysics, 2 Medicine, and 3 Anesthesiology, University of Washington, Seattle 98195; 4 The Mountain-Whisper-Light Statistical Consulting, Seattle, Washington 98122; and 5 Crew Technology Division, Armstrong Laboratory, Air Force Medical Center, Brooks Air Force Base, Texas 78235
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ABSTRACT |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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This study was undertaken to assess the
influence of gravity on the distribution of pulmonary blood flow (PBF)
using increased inertial force as a perturbation. PBF was studied in
unanesthetized swine exposed to
Gx (dorsal-to-ventral
direction, prone position), where G is the magnitude of the force of
gravity at the surface of the Earth, on the Armstrong Laboratory
Centrifuge at Brooks Air Force Base. PBF was measured using 15-µm
fluorescent microspheres, a method with markedly enhanced spatial
resolution. Each animal was exposed randomly to 1, 2, and
3 Gx. Pulmonary vascular
pressures, cardiac output, heart rate, arterial blood gases, and PBF
distribution were measured at each G level. Heterogeneity of PBF
distribution as measured by the coefficient of variation of PBF
distribution increased from 0.38 ± 0.05 to 0.55 ± 0.11 to
0.72 ± 0.16 at 1, 2, and 3
Gx, respectively. At 1
Gx, PBF was greatest in the
ventral and cranial and lowest in the dorsal and caudal regions of the
lung. With increased Gx,
this gradient was augmented in both directions. Extrapolation of these
values to 0 G predicts a slight dorsal (nondependent) region dominance
of PBF and a coefficient of variation of 0.22 in microgravity. Analysis
of variance revealed that a fixed component (vascular structure)
accounted for 81% and nonstructure components (including gravity)
accounted for the remaining 19% of the PBF variance across the entire
experiment (all 3 gravitational levels). The results are inconsistent
with the predictions of the zone model.
fluorescent microspheres; cardiac output; pulmonary gas exchange; centrifuge; acceleration; gravity
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INTRODUCTION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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THE DISTRIBUTION of ventilation and perfusion and, accordingly, the gas exchange function of the lung are governed by a number of gravitational and local (nongravitational) factors. The gravitational model of pulmonary perfusion states that regional perfusion is determined by local alveolar and hydrostatic pressures. The zone model (19) postulates that gravity is the principal determinant of regional perfusion, explaining the observation that perfusion increases from nondependent to dependent lung regions. The zone framework speculates that the blood flow at any isogravitational plane is determined by the balance between alveolar pressure, arterial blood pressure, and venous blood pressure. Because gravity has a greater vertical effect on vascular pressures, the relative zone-pressure relationships, and hence pulmonary vascular flow, vary with vertical height. The gravitational model of pulmonary blood flow (PBF) distribution was developed from studies that measured blood flow to relatively large regions of lung (19, 30). Supporting evidence was provided by Greenleaf et al. (12) and Kaneko et al. (20). More recently, similar gravitational dependence has been seen in humans by use of radioactive 81mKr with an external gamma camera (1, 2), again with limited horizontal resolution. As the spatial resolution of blood flow measurements has improved, experimental observations show less influence of gravity on PBF distribution.
Several investigators have demonstrated isogravitational perfusion heterogeneity. These observations include regional perfusion variability within horizontal planes (25); a radial distribution of flow with the greatest perfusion located centrally in lung lobes (13, 14); and isogravitational perfusion that is increased in dorsal regions regardless of posture, implying an anatomic component (3, 4) to perfusion distribution. Glenny et al. (11) used microspheres to mark perfusion to 1.9-cm3 voxels of lung and concluded that gravity accounts for only 4% of the blood flow distribution in the anesthetized mechanically ventilated dog in the prone or supine posture. This conclusion results from the enhanced spatial resolution offered by the animal experiments in contrast to earlier human experiments with external counters (19). Thus the vast majority of the influences on ventilation and perfusion distribution comes from the local, nongravitational factors.
Previous studies in a high-gravity (inertial force) environment using methods with poor spatial resolution have been interpreted in the context of the zone model. That model suggests that, at the level down the lung where venous pressure exceeds alveolar pressure, the waterfall effect will cease to operate and blood flow will be proportional to the arteriovenous pressure difference. This level then would define the functional transition between zones 2 and 3. Previous work using methods with poor spatial resolution (7) demonstrated that as +Gz (head-to-foot inertial load, where G is the magnitude of the force of gravity at the surface of the Earth)1 increased, the effective waterfall zones (1) were progressively extended downward to regions of higher venous pressure. The zone model also predicts uniform blood flow within isogravitational planes. Furthermore, the effects of increasing alveolar pressure through positive-pressure breathing may enhance this trend, causing the apparent zone 2-3 transition to move even more caudally. West and Dollery (29) obtained data consistent with the interpretation that positive-pressure breathing enlarged zone 2 at the expense of zone 3 and enlarged zone 1 at the expense of zone 2.
We undertook this study to determine the quantitative effect of gravity
on PBF distribution by increasing the magnitude of the gravity vector
in the dorsal-to-ventral direction
(Gx) in unanesthetized
prone pigs using the fluorescent microsphere method with enhanced
spatial resolution. The goal was to quantitate the changes in regional
PBF distribution in response to increased Gx and test the zone model
hypothesis.
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MATERIALS AND METHODS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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This study was approved by the Animal Care Committee of the University of Washington. Animals were managed according to National Institutes of Health regulations and the "Guiding Principles in the Care and Use of Animals" of the American Physiological Society. Four female miniature swine (45.8 ± 3.0 kg) were chemically restrained with ketamine (22-34 mg/kg), intubated, and placed on positive-pressure ventilation (tidal volume 15 ml/kg, frequency adjusted to maintain arterial PCO2 between 35 and 40 Torr) with ~1% isoflurane (to effect). A surgical plane of anesthesia was maintained at all times while the catheters were being placed. Two Swan-Ganz catheters (5- and 7-Fr in 2 animals and two 7-Fr in 2 animals) were introduced into each jugular vein and advanced under fluoroscopy into the pulmonary artery. The pulmonary arterial catheters were used for determination of cardiac output (thermal dilution) and core body temperature, withdrawal of a reference pulmonary arterial blood sample, and measurement of pulmonary arterial pressure and central venous pressure. The proximal port of one of the Swan-Ganz catheters was used for microsphere injection. A catheter was placed into the right carotid artery for measurement of arterial blood pressure and determination of arterial blood gases. An esophageal balloon was introduced to monitor respiration and intrathoracic pressure. Surgical sites were infiltrated with 2% bupivacaine, animals were given 5,000 IU of heparin, and electrocardiogram leads were attached. The animals were fitted with a swine antigravity suit and placed in the prone position in a form-fitted fiberglass couch. Lateral thoracic X rays were taken for lung position. The animal and couch were transported to the centrifuge facility, and the couch was attached to the animal arm of the Armstrong Laboratory Centrifuge.
Fluorescent 15-µm-diameter microspheres (blue-green, yellow-green, orange, and red; Molecular Probes) were used to measure regional PBF. Their excitation and emission spectra allow them to be easily separated, providing a method for measuring regional organ perfusion at multiple time points or physiological conditions. Techniques for injection of microspheres into conscious animals undergoing centrifugation have been previously developed and successfully employed (22, 31). The remote-control infusion system consisted of an infusion pump (model 600-000, Harvard Apparatus) and a catheter (injection link) containing a suspension of 2 × 106 microspheres in saline, dextran, and Tween 20 (0.2% solids in 2 ml). The solution containing microspheres was modified to have exactly the specific gravity of the microspheres (1.04) to ensure uniform suspension during centrifugation. A small air bubble isolated the microspheres on both sides from 1 ml of saline dead space to conserve this specific gravity. By remote control the microspheres were pumped into the proximal port of the Swan-Ganz catheter. This allowed the microspheres to be injected over approximately four to six breaths.
Once fully awake, the animals were exposed randomly to 1,
2, and 3 Gx while
prone (with head toward the center of the centrifuge) (Table
1). An exposure of one of the G levels was
repeated, but the repeated data are not analyzed here. The animals were
placed in the horizontal contoured platform (prone position) with the
head toward the center of rotation. The platform was allowed to pivot,
with the center of mass of the platform directly below the pivot axis
of the platform. As the centrifuge began to rotate, a radial component
of force, coupled with the fact that the center of mass of the pig and
the platform were below the center of rotation of the platform,
resulted in a pivoting of the animal platform, with the head of the pig
rotating downward to the floor and the tail of the pig rotating in the
upward (skyward) direction (Fig. 1). The
net force (gravity and the radial centifugal force) and the pivoting of
the animal result in a net force in the
Gx direction
(dorsal-to-ventral; same direction as in the resting prone position).
For each G exposure, once the centrifuge reached a stable G plateau and
the animal reached a quasi-steady state in terms of arterial pressure
and breathing patterns, simultaneous withdrawal of 5 ml of arterial
blood for blood-gas determination from the carotid catheter and
injection of iced saline through the Swan-Ganz catheter for
thermal-dilution cardiac output measurement were performed by remote
control. Outputs from the Swan-Ganz temperature probe were connected to
a cardiac output computer (Baxter Healthcare). After these
measurements, the microspheres were injected at a rate of ~4 ml/min
(~30 s) via the proximal port of the Swan-Ganz catheter. Reference
blood samples (10 ml) were withdrawn from the distal port of the
Swan-Ganz catheter at a rate of 4.94 ml/min. Between each G exposure,
the centrifuge arm was stopped, the next set of microspheres was
placed in the injection link, and the blood-gas and reference blood
samples were retrieved. Blood gas
PO2,
PCO2, and pH were measured with a
Corning model 158 blood-gas electrode system.
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After the experiment the animals were deeply anesthetized, intubated, ventilated, and given 10,000 IU of heparin and 350 mg of papaverine intravenously. The animals were exsanguinated via the arterial catheters, and intravascular volume was replaced with normal saline containing heparin. Once sufficiently hemodiluted, the animals were euthanized with pentobarbital sodium. A thoracotomy was performed, large-bore catheters were placed into the left atrium and pulmonary artery, and the thoracic aorta was occluded. The lungs were perfused with 2% dextran in saline until clear of blood, removed from the chest, reinflated, and allowed to dry on warm continuous positive airway pressure of 25-30 cmH2O for several days. Samples of heart and kidney were removed to determine whether shunting of the microspheres through the lungs occurred.
When dry, the lungs were suspended vertically in a plastic-lined square box and embedded in rapidly setting urethan foam to provide a rigid coordinate system. The lateral chest X ray was used to align the lungs in the box so that slicing produced true isogravitational planes. With use of a miter box, the foam block was cut into uniformly sized cubes (n = 2,315 ± 59), 1.9 cm3 in volume. An average of 6.6% of the pieces were discarded (airway >25% of volume). Weight, spatial coordinates, and lobe designation for each piece were recorded. Lung pieces were soaked in 1.5 ml of 2-ethoxyethyl acetate to dissolve the microspheres, and the released fluorescent dye was measured on a Perkin-Elmer LS-50b luminescence spectrophotometer.
Data processing. Relative blood flow to each piece was calculated by dividing the flow to each piece at each level of G force by the mean flow per gram of all pieces at that level of G force. Weight-normalized relative blood flow (WNRF) was then determined by dividing the relative blood flow of each lung piece by the weight of that piece. The distance from each lung piece to the hilum (Dh) was calculated from the spatial coordinates of each piece2
![D<SUB>h</SUB> = [(<IT>x</IT> − <IT>x</IT><SUB>h</SUB>)<SUP>2</SUP> + (<IT>y</IT> − <IT>y</IT><SUB>h</SUB>)<SUP>2</SUP> + (<IT>z</IT> − <IT>z</IT><SUB>h</SUB>)<SUP>2</SUP>]<SUP>0.5</SUP>](/content/vol84/issue4/fulltext/1278/img001.gif)
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(1) |
Statistics. Four features of flow distribution were calculated: 1) heterogeneity of perfusion was characterized by the coefficient of variation (CV); 2) linear gradients in flow were expressed as regression slopes for relative flows vs. x (ventral-to-dorsal direction), y (right-to-left direction), z (cranial-to-caudal direction), and Dh; 3) the variation in flow was classified into two components, that portion determined by biological structure (piece effect) and the balance of flow variation that changed across gravitational levels; and 4) the center of flow was determined as the weighted mean of x, y, and z (separately), where the weights were the WNRF for each piece.
The CV was calculated as the standard deviation of flow within a pig at a specified G divided by the mean flow for the same condition. The CV was expressed as a percentage. We analyzed the relationship of heterogeneity (CV) and slopes to gravity using simple linear regression, with gravity as the independent variable and slope or CV as the dependent variable. A simple linear regression model of flow vs. each spatial distance (x, y, z, or Dh) was performed, yielding the gradient of flow (dWNRF/ddistance) vs. each dimension for each pig at eachGx level. The relation of
these gradients to G was calculated for each animal using linear
regression with gradients (e.g., gradient of flow in the
y direction) as the dependent variable and G as the independent variable.
We partitioned the variation in relative flow across gravitational
states into 1) a component due to
position of the piece within the lung (represented by pieces) and
2) a component representing the
combination of gravitational states, variation over time, and
methodological noise. The component of variation due to position can be
thought of as variation arising from a biological pattern enduring
across the gravitational states being considered. The second component
of variation represents the changeable portion of flow across changes
in gravity states (redistribution + changes over time) plus random
variation due to the microsphere method.
The variance component due to changes in flow across G levels, time,
and methodological noise
(
) was estimated by
|
(2) |
i
is the mean relative flow for piece i
across the different G levels considered,
n is the number of states, and
m is the number of pieces. The
variance component due to pieces was estimated by
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(3) |
has a value of 1.0 because
of normalization of flow, as described earlier.
Because the variation across pieces and the variation across
gravitational states (including time and methodological noise) are the
only sources of variation in flow, their relative contributions to the
total variance can be calculated as percentages. The percentage of
variation across pieces is as follows:
Ppieces = 100 · 
/( + ). The percent variation
across gravitational states is PG = 100 Ppieces. The negligible methodological noise contributes primarily to
and
slightly to
.
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RESULTS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Physiological data.
Basic physiological data for the animals are shown in Table
2. With increasing
Gx, gas exchange worsened,
as indicated by a decrease in arterial
PO2 from 94.9 to 43 Torr. Hypoventilation was indicated by the increased arterial
PCO2 (48.7 Torr) at 3
Gx. At 3
Gx, an acceptable arterial blood sample was obtained in only one animal because of problems with the
automatic blood sampler. Cardiac output was determined from the
fluorescent microspheres using a reference withdrawal pump (see Ref. 11
for details) and from thermodilution. The thermodilution method did not
work well at higher G levels, because the temperature did not return to
baseline, disabling the cardiac output calculation. We relied on the
microsphere cardiac output, which increased at 3
Gx in a manner that paralleled
the increase in heart rate.
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Heterogeneity.
The histograms shown in Fig. 2 demonstrate
the distribution of WNRF. For pig 2 at
1 Gx, the distribution is
centered on a normalized flow of 1.0. As the
Gx level increases (Fig.
2, B and
C), the overall heterogeneity
increases, as indicated by the broader histograms and larger CVs of
flow, and become more skewed, as indicated by the asymmetry. At
3 Gx, ~10% of lung
pieces had a near-zero WNRF. These pieces tended to be in the most
dorsal regions of the lung.
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1, 2, and
3 Gx, respectively. The increase in heterogeneity with increased
Gx is shown in Fig.
3. The increase in CV with gravitational
force was very well fit in each animal with a linear model with
R2 ranging from
0.90 to 1.0. Extrapolation of the linear regression model for each
animal allows estimation of the magnitude of heterogeneity of PBF that
might be expected at 0 G (mean CV = 22 ± 3%). The CV increases by 17 ± 6% per unit
increase in G.
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1, 2, and 3
Gx in Fig. 4, A,
B, and C,
respectively. In Fig. 4, there is a considerable amount of
heterogeneity of PBF within each isogravitational plane, a
characteristic finding when higher-resolution methods are used to
measure regional PBF (i.e., variability is not due to methodological
noise). At 1 Gx (Fig.
4A), a fitted regression line shows
a slight gravitational gradient (greater flow in the ventral regions). As Gx level increases,
blood flow shifted in the ventral direction, as shown by the
increasingly steeper fitted regression lines, indicating greater
gravitational gradients.
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Gx level is
shown in Fig. 5 and Table
3. Each point in Fig. 5 represents the
slope (gradient) of normalized flow with vertical distance for a
specified pig at a specified G force. The
x gradient of the regression line for
flow vs. vertical distance up the lung becomes more negative (net shift
ventrally) with increasing
Gx. Extrapolation of the
linear fit line to 0 G reveals no net vertical dependence of blood flow
(intercept of 0.010 ± 0.017) in the
absence of gravitational inertial force. The vertical gradient steepens
by 0.035 ± 0.008 relative flow unit per centimeter for every G
unit.
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1
Gx (Fig.
6A). The mean gradient for all animals was 0.037 relative flow unit per centimeter. This radial gradient increased in magnitude substantially as the G force increased (Fig. 6, B
and C).
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0.013 ± 0.019 and a change per unit
G level of 0.029 ± 0.008, showing no significant radial
gradient of PBF after elimination of
Gx load.
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0.95, indicating a good fit by the linear models for gradient vs.
G. Table 4 shows large changes in gradients as G increases. The
ventral-dorsal, caudal-cranial, and hilar gradients change significantly with G (P < 0.05, t-test), and the change in the left-right gradient is small and nonsignificant. The largest change with G occurs for the ventral-dorsal gradient, where a one-unit increase in G, e.g., from 1 to 2, would increase the gradient by 0.035 relative flow unit per centimeter. Thus a lung region that was 10 cm
more ventral than a comparable dorsal region would have a flow that
increased by 0.35 more than the dorsal regions for the 1-G change.
Given a mean flow of 1.0, the regional contrast is substantial.
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DISCUSSION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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The important findings of this study are as follows:
1) regional PBF becomes more
heterogeneous with increasing
Gx force;
2) extrapolation of observations to
0 G indicates persistent perfusion heterogeneity in microgravity; and
3) a fixed structural component is
the major determinant of regional perfusion across all
Gx levels.
Methodological issues.
To estimate regional PBF reliably, the fluorescent microsphere method
must fulfill several criteria. First, the microspheres must have a
distribution in the microcirculation similar to whole blood. These
15-µm microspheres have a density (1.04 g/dl) very close to blood and
have recently been validated for measurement of regional PBF in dogs
(10). In addition, Laughlin et al. (22) showed that radiolabeled
microspheres of even greater density (1.23 g/ml) are suitable for use
at high acceleration levels. Second, the number of microspheres have to
be large enough to limit the effect of method error on the statistics.
We injected 2 × 106
microspheres per injection, which provided >400 microspheres per
tissue sample when blood flow was 25% of average flow.
Ppl, where
PA is alveolar pressure and Ppl
is pleural pressure, the absence of a pleural gradient in the prone
position confirms that alveolar volumes are uniformly distributed down
the lung in a prone pig (at 1 Gx).
The configuration of the lung after it is dried may be slightly
different from that in vivo. Lung drying occurs during suspension from
the trachea with a pressure of 25-30
cmH2O; therefore, lung volume will
be slightly greater than in the intact lung. This will increase linear
dimensions slightly. Because lungs dry during suspension from the
trachea, the orientation of gravity is different, possibly resulting in
a slight distortion relative to the intact lung. The shape of the lung
will be slightly different from that of an in vivo lung because of the
lack of physical constraints of the chest wall and diaphragm. It is
also possible that in the chest the weight of the heart may result in
some compression of any lung below it. The volume of this ventral lung
is quite small and would have little influence, if any, on the
regressions. Even though these factors are difficult to quantitate,
they are expected to be quite unimportant with respect to the major
findings of this study.
The average CV of PBF for the four pigs at
1Gx was 38%
(1.9-cm3 piece). This is within
the range of other studies of PBF heterogeneity. Melsom et al. (23)
examined distribution of PBF in horizontal lung slices in awake goats
and found a mean heterogeneity of 38% (1.5-cm3 piece)
without considering the effect of vertical differences, which likely
would have slightly increased apparent heterogeneity. Parker et al.
(27) observed a mean heterogeneity of 47%
(1.0-cm3 piece) in awake
chronically catheterized dogs, and Glenny et al. (11) found a mean
heterogeneity of 45% in the supine position and 41%
in the prone position (1.9-cm3
piece) in halothane-anesthetized prone dogs. We found a CV of 31%
(1.9-cm3 piece) in Thoroughbred
horses (5, 15) and 30%
(1.7-cm3 piece) in
lambs (28). In this study, heterogeneity increased substantially with
increasing inertial force in pigs.
The distribution of PBF vs. height up the lung (Fig. 4) is only
slightly dependent on vertical position (vertical slope = 0.20
WNRF/cm, Table 3). This is consistent with the zone model in direction
but not in magnitude. The apparent gravity dependence (as shown by the
mean PBF in each isogravitational plane) increases with increasing
Gx (Table 3). This change
in mean flow is consistent with predictions of the zone model.
The pigs in this study demonstrated a large degree of isogravitational
heterogeneity at all three
Gx levels (prone position;
Fig. 4A). This observation is not
consistent with the zone model. The magnitude of isogravitational
heterogeneity increased with increasing
Gx to a maximum at
3 Gx (Fig. 4C) in all animals. It is this
isogravitational heterogeneity that argues most strongly against the
relevance of the zone model. If gravity and the "hydrostatic
column" in the arterial and venous blood vessels are the dominant
features in determining PBF distribution, then this very large
heterogeneity in isogravitational planes is impossible.
Another curious feature of the vertical PBF distribution (Fig. 4) is
the nonlinear shape at each
Gx level. This shape is
accentuated with increasing
Gx, with a decrease in
flow in the dorsal and ventral regions. The decrease in flow in the
ventral regions is surprising, with the prediction of an increased
hydrostatic pressure with increased acceleration. The large decrease in
flow in the ventral regions may be due to alveolar collapse and related
increase in vascular resistance. Another potential explanation is that
alveolar collapse may cause venous closure, causing vascular trapping
of blood in capillaries and/or venules. With the decrease in
flow in the dorsal and ventral regions, PBF is shifted toward the
vertically middle regions. The mean flow and the range of variation of
WNRF increase with increased Gx in the middle regions.
The PBF distribution demonstrates a significant radial component (Fig.
6) that steepens with increasing
Gx. The PBF in peripheral
(most distant from the hilum) regions is decreased relative to the mean
PBF. In these prone pigs the most distant regions are largely within
the dorsal-caudal regions of the lungs. The increased force of
acceleration may cause physical distortion of the most dorsal alveoli,
resulting in increased vascular resistance and decreased PBF.
The mean flow in isogravitational planes is similar to that shown in
human subjects by Bryan et al. (6). Figure
8 shows data from human subjects with
perfusion measured using macroaggregated albumin labeled with
131I. The percent flow
(representing counts) is shown for injections performed in the seated
position at +1, +2, +3, and +4 Gz (cranial-to-caudal inertial force). An external scintillation scanner
was used to measure total blood flow across the chest in a given
region. As in our study, the distribution of blood flow was determined
after return to 1 G. Each curve represents one
injection in a different subject. These authors demonstrated an
apparent downward (in the direction of the G vector) shift of the
horizontally averaged blood flow, with a decrease in flow in the upper
regions and an increase in flow in the lower regions. However, the
downward shift of peak flow is surprisingly small for increased
Gz level.
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1, 2, and
3 Gx, with the upper and
lower regions oriented similar to the orientation in the data of Bryan
et al. (6) (Fig. 8). The general shapes of the curves are similar.
There is a shift of the average blood flow in the direction of the G
vector. If totaled across the lung in isogravitational planes
(Fig. 9), our data would appear consistent with the
zone model, as was interpreted by Bryan et al. in seated human
subjects. However, the individual piece flow distribution (Fig.
4A) demonstrates a heterogeneity in
the isogravitational planes. This isogravitational heterogeneity cannot
be explained by the zone model.
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Gx unit. Although the
pattern of change is similar, the magnitude is smaller in the pigs,
even though the height of the lung in the prone pig is comparable to that in the seated human. This magnitude difference may be due to the
difference in species or the different orientation of the G vector
relative to the lung orientation:
Gx in our pig studies and
+Gz in Glaister's study. Another
potential factor consists of the smoothing and edge effects of the
scintillation counter methodology, causing distortion of the human
data.
An example of the change in WNRF from 1 to 3
Gx is shown in Fig.
10. Figure
10A shows a shift from the left to the right sides. Figure 10B plots the
change in flow vs. height up the lung in the vertical direction. WNRF
decreased near the ventral and dorsal surfaces, whereas flow increased
in the central regions. Figure 10C
shows more of the decreased flow in the caudal regions. Thus the
regions with decreased flow tended to be in the dorsal and caudal
regions and more distant from hila in the radial direction (Fig.
10D).
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Gx level increased,
the dorsal, caudal, and ventral peripheral regions of the lung likely
became distorted. The dorsal caudal regions are stretched
and the ventral regions collapsed, likely resulting in an increase of
regional pulmonary vascular resistance in both regions. As shown in
Fig. 10, the more dorsal regions had a reduced PBF with 3
Gx. The central regions had an increased PBF with 3
Gx. Because total PBF increased
slightly with Gx, the PBF
shifted toward the lower-resistance hilar regions of the lung. This
results in an increase in the radial gradient of PBF distribution, as
shown in Fig. 6.
The center of flow is calculated as a spatial average of the flow
determined for the x, y, and
z coordinates with an arbitrary origin
in centimeter units. With increased inertial force, the center of flow
shifts in the direction of the inertial force as modified by
parenchyma-dependent distortions. Table 6
lists the mean shift in center of flow in each of the three axes for
the four pigs. The overall shift in center of flow with increasing inertial force is in the right, ventral, and cranial directions.
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Gx levels. If the zone
model were to dominate flow, it would be expected that the variation in
flow within each volume would be much larger than the variation among
specific regions.
Despite the observation that pulmonary blood shifts markedly with
increasing inertial force when external scintillation counters are
used, the data from finer spatial resolution show a remarkable similarity of flow within each region. When the inertial force is
increased threefold, the PBF distribution changes minimally. Less than
19% of the flow variance results from the increased gravitational force.
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ACKNOWLEDGEMENTS |
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We are indebted to Wayne Isdahl, Jim Hartman, Charles Kuhnel, and Jemett Robinson (Brooks Air Force Base) and Dowon An and Erin Shade (Seattle, WA) for excellent technical assistance. In addition, we thank Lt. Col. John Fanton and Laura and Karen Lott for support with the surgery procedures. We appreciate the advice of Dr. Ted Wilson regarding issues of parenchymal displacement.
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FOOTNOTES |
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The animals involved in this study were procured, maintained, and used in accordance with the Animal Welfare Act and the "Guide for the Care and Use of Laboratory Animals" prepared by the Institute of Laboratory Animal Resources-National Research Council. Armstrong Laboratory is accredited by the American Association for Accredidation of Laboratory Animal Care.
This research was supported, in part, by National Heart, Lung, and Blood Institute Grants HL-12174 and HL-24163 and by internal support from the US Air Force at Brooks Air Force Base.
1
In keeping with the standard notation in
acceleration research, we use the three vectors of G force as follows:
x (ventral to dorsal),
x (dorsal to ventral),
y (right to left),
y (left to right),
z (cranial to caudal), and
z (caudal to cranial).
2 The x, y, and z directions for lung spatial locations are identical to the G vector directions in this report. In previous reports from our laboratory, we switch the x and y coordinates. Care should be taken when spatial distributions are compared with our previous articles.
Address for reprint requests: M. P. Hlastala, Div. of Pulmonary and Critical Care Medicine, Box 356522, University of Washington, Seattle, WA 98195-6522.
Received 29 April 1997; accepted in final form 8 December 1997.
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REFERENCES |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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1.
Amis, T. C.,
H. A. Jones,
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