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Departments of 1 Physiology and Biophysics, 2 Medicine, and 3 Anesthesiology, University of Washington, Seattle, Washington 98195; 4 Center for Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40506; and 5 Division of Chest Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical School, Taipei, Taiwan
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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We aimed to assess the influence
of lateral decubitus postures and positive end-expiratory
pressure (PEEP) on the regional distribution of ventilation and
perfusion. We measured regional ventilation (
A) and
regional blood flow (
) in six anesthetized, mechanically
ventilated dogs in the left (LLD) and right lateral decubitus (RLD)
postures with and without 10 cmH2O PEEP. was measured by use of intravenously injected 15-µm fluorescent
microspheres, and A was measured by aerosolized
1-µm fluorescent microspheres. Fluorescence was analyzed in lung
pieces ~1.7 cm3 in volume. Multiple linear regression
analysis was used to evaluate three-dimensional spatial gradients of
, A, the ratio A/, and regional PO2 (PrO2) in
both lungs. In the LLD posture, a gravity-dependent vertical gradient
in was observed in both lungs in conjunction with a reduced
blood flow and PrO2 to the dependent left lung. Change
from the LLD to the RLD or 10 cmH2O PEEP increased local A/ and PrO2 in the left lung
and minimized any role of hypoxia. The greatest reduction in individual
lung volume occurred to the left lung in the LLD posture. We conclude
that lung distortion caused by the weight of the heart and abdomen is
greater in the LLD posture and influences both and
A, and ultimately gas exchange. In this respect, the
smaller left lung was the most susceptible to impaired gas exchange in
the LLD posture.
pulmonary gas exchange; spatial gradients; fluorescent microspheres; mediastinal shift; regional blood flow; positive end-expiratory pressure
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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STUDIES (11,
33) HAVE SUGGESTED that regional blood flow
() and ventilation (A) are more uniform in
the prone compared with the supine posture. This was attributed to
greater and A to the dorsal lung regions,
offsetting the effects of gravity. Also, the reduction in the dependent
lung volume by the weight of the heart might contribute to differences
in regional perfusion and A (3). In the
lateral decubitus posture, the compression of the dependent lung by the
heart might be greater than that in either supine or prone posture.
Furthermore, the dependent lung has a smaller lung volume in the left
(LLD) than in the right lateral decubitus (RLD) posture
(35), consistent with differing effects of the heart
between the two postures.
increases from the nondependent to dependent lung in the
lateral decubitus posture in the human (6, 25, 28) and the
dog (20, 37). In addition, the intrapulmonary ventilation distribution is altered in the lateral posture after anesthesia and
mechanical ventilation (38, 39). Impaired gas exchange after anesthesia and mechanical ventilation has been attributed to a
mismatch between ventilation and perfusion. The relative matching of
pulmonary blood flow and ventilation distribution in lateral decubitus
postures remains uncertain.
Positive end-expiratory pressure (PEEP) is often applied to improve
arterial oxygenation during anesthesia with mechanical ventilation
(28, 38, 39). In the lateral posture, PEEP has been shown
to reduce the difference in ventilation between the two lungs
(39). In these studies (28, 38, 39),
ventilation was measured in relatively large regions, such as a single
lobe or lung. Accordingly, direct evidence using a high spatial
resolution measure of the A distribution in the
lateral decubitus posture after induction of anesthesia with PEEP is lacking.
We hypothesize that the distributions of A and
are different between the LLD and RLD posture because of
differences in lung distortion caused by the weight of the heart and
abdominal contents. PEEP reduces lung distortion due to heart weight,
may affect the smaller left dependent lung to a greater degree, and produces a larger decrease in pulmonary vascular resistance in the LLD
posture. PEEP may increase both A and to
dependent lung regions, particularly to the dependent left lung in the
LLD posture.
This study examines the effect of posture and PEEP on ,
ventilation, and gas exchange in the lateral decubitus posture in anesthetized, mechanically ventilated dogs, using both aerosolized and
intravenously injected fluorescent microspheres.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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Animal Preparation and Physiological Measurements
This study was approved by the University of Washington Animal Care Committee. Six healthy mongrel dogs of either sex [22.8 ± 2.8 (SD, n = 6) kg] were anesthetized with pentobarbital sodium (~4-8 mg/kg iv) and maintained with a pentobarbital infusion sufficient to achieve a surgical plane of anesthesia and eliminate spontaneous ventilation (~10-17 mg · kg
1 · h1). Dogs were
mechanically ventilated with air via tracheostomy [tidal volume
(VT) of 15 ml/kg]. The respiratory rate was adjusted to
maintain arterial PCO2 (PaCO2)
between 35 and 40 Torr. Minute ventilation was measured with a
spirometer. Catheters were placed in one femoral artery and both
femoral veins. A pulmonary artery catheter was introduced into the
right external jugular vein and used for measuring cardiac output
(T; thermal dilution) and core temperature (Tc).
Systemic arterial (Pa), pulmonary arterial (Ppa), pulmonary capillary
wedge (Ppcw), and airway pressure (Paw) were recorded continuously on a
data management system (Western Graphic Mach 12 DMS 1000). For
determination of anatomic dead space (VD), exhaled
end-tidal PCO2 was digitally sampled with an
infrared CO2 detector (Perkin-Elmer, Plumsteadville, PA),
and expiratory airflow () was measured by pneumotachograph.
Arterial and mixed venous blood gases were measured with an automated
blood-gas analyzer (ABL 300, Radiometer, Copenhagen, Denmark) and
corrected for temperature. Body temperature was maintained by using
heat lamps and pads.
Study Protocol
Animals were studied in the right and left lateral decubitus postures with 0 or 10 cmH2O PEEP, in random order. The lungs were fully inflated (30-40 cmH2O) 5 min before each experimental measurement to remove atelectasis. In each trial, we measured Pa, Ppa, Ppcw,T, Tc, VT, and
arterial and venous blood gas composition immediately before
fluorescent microsphere administration. was measured with
intravenously injected microspheres, and A was
measured with fluorescent aerosols as described below. Functional
residual capacity (FRC) was measured by He dilution during each
experimental condition.
Multiple Inert Gas Measurements
Pulmonary gas exchange was characterized and analyzed by MIGET, the multiple inert gas elimination technique (46, 47). Distributions of ventilation-perfusion ratio (A/) were estimated by use of a
50-compartment model (47). Inert gas shunt
(S/T) and dead space
(VD/VT) were obtained from the model. Data from five of six animals are presented since one animal was rejected because
of the presence of technical errors.
Fluorescent-labeled Microsphere Technique
A was measured in both the LLD and RLD
posture with and without PEEP by delivering aerosolized orange,
orange-red, yellow, or yellow-green 1-µm-diameter fluorescent
microspheres (FluoSpheres, Molecular Probes, Eugene, OR) into the
ventilator circuit during a 5-min period (40).
Simultaneously, was measured by injecting blue-green, green,
crimson, or red 15-µm-diameter fluorescent microspheres via the
femoral venous catheter, in five increments over the 5 min. To avoid
clumping, microspheres were sonicated and vortexed before
administration. Microsphere colors were randomly varied across experiments.
Terminally, the animals were deeply anesthetized with pentothal (150 mg/kg iv); then saline, heparin (20,000 units), and papaverine (2 mg/kg) were administered. The animals were exsanguinated via the arterial cannula. After a median sternotomy, the left atrium and pulmonary artery were cannulated, the aorta was tied off, and the lungs were perfused with 2% dextran solution to remove the blood. The lungs were removed and dried by inflation (~25 cmH2O) to total lung capacity (TLC). The pleura was pierced in several locations with a needle to facilitate drying. To maintain a normal anatomic configuration, the apical and most ventrocaudal rims of the left and right lungs were joined by tissue glue.
After 7 days, the dried lungs were coated with polyurethane foam (Kwik Foam, DAP, Dayton, OH) and placed in a plastic-lined square box with the caudal-cranial axis of the lung parallel to the wall of box. The box was filled with a rapidly setting foam (Polyol and isocyanate, International Sales, Seattle, WA). The solid block was sliced into 1.2-cm-thick slices. With use of a miter box, the lung slices were diced into cubes with 1.2-cm sides. Each lung piece was weighed and assigned x0, y0, and z0 coordinates measured from the left, dorsal, and caudal lung edges, representing the left-right, dorsal-ventral, and caudal-cranial axes, respectively. Samples <0.008 g were discarded. Fluorescent dye was extracted by soaking each piece in 1.5 ml 2-ethoxy ethyl acetate (Cellosolve, Aldrich Chemical, Milwaukee, WI) for 4 days. Dye concentrations were measured with an automated luminescence spectrophotometer (Perkin-Elmer, model LS-50B, Norwalk, CT) at the dye-specific excitation and emission wavelength. A matrix inversion method (42) was used to correct the fluorescent signal spillover from adjacent colors.
Data Processing
Adjusting cube dimensions from TLC back to in situ FRC conditions. To estimate spatial gradients in blood flow and ventilation per regional lung volume at the time of microsphere injection, the dimensions of each cube were adjusted from their TLC measurements to estimated in vivo values using previous measurements from anesthetized dogs (20, 37). In the LLD posture, the ratios of the maximum lung lengths at FRC to those at TLC measured radiographically were 0.68 (0.85 in RLD posture), 0.76, and 0.84 in the vertical (x), dorsal-ventral (y), and caudal-cranial (z) axis, respectively. Adjusted vertical heights at FRC averaged 11.1 ± 0.9 and 14.0 ± 1.2 cm in the LLD and RLD posture, respectively, without PEEP; and 16.4 ± 1.5 cm for both postures with PEEP. The adjusted dorsal-ventral and caudal-cranial lengths averaged 13.1 ± 1.1 and 23.9 ± 2.3 cm, respectively.
A second adjustment was made for the nonuniform deformation caused by the vertical gradient in transpulmonary pressure (Ptp). At the adjusted lung height xi measured from the bottom of the lung, (Ptp)i is given by
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(1) |
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(2) |
Ptp)i is the Ptp change from the value at
Vmin and (Ptp)max is the maximum change in
Ptp from Vmin to Vmax. We assumed that the PV
curve is linear in this Ptp range. Vmin (20% TLC) is the
lung volume at (Ptp)min at the bottom of the lung
xmin. Vmax (65%TLC) is the lung
volume at (Ptp)max. The cube at mid-lung height
(xmid), equal to
(xmax + xmin)/2, is
assumed to remain undistorted (u) with a cube length equal
to the value after the reduction from TLC to FRC (xu).
The deformed length (xi) for the ith cube at
xi is assumed to vary as V1/3, given by the PV
curve, at each (Ptp)i
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(3) |
xi/xu (Eq. 3).
We assumed no vertical Ptp gradient in the lateral position with PEEP
(2). In addition, lung volume at 10 cmH2O PEEP
was ~85% TLC; thus cube length (proportional to V1/3)
was 0.95 times the cube length at TLC. Accordingly, no adjustment was
made to the dried lung lengths at 10 cmH2O PEEP.
Volume normalization of blood flow.
Fluorescent intensity of each color microsphere representing or
A to each piece (cube) was converted to units of
blood flow (ml/min) by dividing the fluorescence intensity of each
piece by the sum of the fluorescent intensities of all pieces and then multiplying by T (ml/min). and
A of each piece were then converted to units of
milliliters per minute per unit regional lung volume at FRC by dividing
by its volume (Vi). Vi at xi was calculated from its dry weight Wi, mean lung density (
),
and the deformed cube length (Eq. 3)
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(4) |
xi/xu)3
adjusts the mean density for changes due to the Ptp gradient. The
product of Wi and 4.7, lung wet-to-dry-weight ratio
(43), is the wet weight. Mean lung density at FRC was equal to total lung wet weight (total dry weight × 4.7) divided by total lung volume at FRC (air volume; FRC + volume of tissue mass). Tissue density was 1 g/ml. The measured FRC values are summarized in Table 1. Lung dry weight
averaged 10.1 ± 0.7 and 13.6 ± 0.95 g for the left and
right lung, respectively. Left lung weight was 24% smaller than right
lung weight. Mean lung density averaged 0.14 ± 0.02 and 0.08 ± 0.01 g/ml at FRC and 10 cmH2O PEEP, respectively.
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Gas exchange parameters: A/ and
PO2.
The A/ was used to calculate end-capillary
PO2. We used the method described by Altemeier
et al. (4) to calculate arterial PO2, PCO2,
alveolar-arterial O2 differences
(A-aDO2), and regional PO2 (PrO2) from the measured
A and fluorescent intensities, Hb
concentration, body temperature, and mixed venous blood gases. With the
measured A/ for each piece, the
mass balance equations for O2, CO2, and
N2, end-capillary O2, and CO2
contents were solved to obtain regional alveolar
PO2 and PCO2 for each
piece. Regional alveolar gas tensions of each piece were ventilation
weighted, and end-capillary gas contents were perfusion weighted and
summed to yield mixed alveolar gas tension and mixed arterial gas content.
Statistical Analysis
and A per unit regional lung volume
were used for all analyses. Values were presented as means ± SD.
A paired t-test was used to evaluate a difference between
two groups. ANOVA was used to evaluate differences among more than two
groups. A P value < 0.05 was considered significant.
Spatial variations using multiple linear regression analysis.
A multiple linear regression model (StatView v. 5.0.1, SAS) was used to
characterize the magnitude of (and other variables A, A/, and
PrO2) as a linear function of the rectangular coordinates, x [vertical height in the left (or right)
lateral posture, left-to-right (or right-to-left) direction],
y (dorsal-ventral direction), and z
(caudal-cranial direction)
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(5) |
with respect to x results in the following
equation describing the blood flow gradient in the x direction
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(6) |
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(7) |
A/ heterogeneity.
We evaluated the heterogeneity of A, and
A/ distributions using the coefficient of
variation (
), the standard deviation of regional
A and values divided by mean values.
Variance (2) of A/ was
computed from the variances of A and with Pearson's correlation coefficient (c) between
A and (50)
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(8) |
A/ measured by the
log-normal standard deviations (lnSDA and
lnSD) of A- and
-A/ distribution curves was obtained
from MIGET and the fluorescent microspheres (FMS) data.
To separate the heterogeneity in A, , and
A/ due to spatial variations from that due to
other factors (residual variation), the variance (mean summed squares)
of the mean summed square of the residuals, (measured 
predicted
values)/mean value (50), was obtained from the multiple
linear regression analysis. This analysis was repeated using a
fourth-order regression equation (31 terms) with terms up to third
order in each coordinate and up to fourth order in each term
(xpyqzr,
p + q + r 
4). Preliminary
analysis indicated no further decrease in the residual variance (or
increase in R2) with a higher order regression
equation. The residual variance/total variance equals 1 R2, where R2 is the
adjusted coefficient of determination from the regression analysis.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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Physiological Data
Table 1 summarizes the physiological data. Body position and PEEP had no effect onT, heart rate, temperature,
respiration rate, pH, mixed venous PO2, and
hemoglobin. PEEP decreased Psa and increased Ppa, Ppcw, and peak Paw in
both LLD and RLD postures. Arterial PO2
(PaO2) was greater in the LLD than RLD posture,
whereas A-aDO2 was less in the LLD than RLD
posture. The addition of PEEP increased PaCO2 by ~2
Torr in both postures. PEEP increased FRC by 65 and 76% in the LLD and
RLD postures, respectively.
S/T and
VD/VT showed no change between the LLD
(0.15 ± 0.3 and 43.5 ± 4.8%) and RLD (0.18 ± 0.24 and 43.6 ± 4.6%) postures. PEEP increased
VD/VT in both the LLD (49.1 ± 8.5%) and
RLD (48.9 ± 6.7%) postures and decreased
S/T in the LLD (0.03 ± 0.05%) but not the RLD (0.15 ± 0.24%) posture.
S/T was similar to that measured
by the FMS data. VD/VT was greater than that
measured by Fowler's method (Table 1).
Microsphere data.
In total, 1,378-1,654 lung pieces per animal were processed for
and A. We discarded lung pieces
(135 ± 49) with >25% pulmonary airways and with fluorescent
intensity (11 ± 10) outside the range of ±4 SD of any of the
mean values. Analysis of blood flow and ventilation was carried out on
90.4 ± 5% of the total lung pieces. For the analysis of
A/ and PrO2, we accepted data with the range of mean ± 3 SD of
ln(A/). This eliminated the pieces associated
with dead space (very large A/) and with
shunt (very low A/). The number of pieces
eliminated averaged 3 ± 4% of the total.
Spatial Gradients in , A,
A/, and PrO2
, A, A/, and
PrO2 for all conditions. The use of the equation was
further justified because R2 for the best-fit
regression was lower when only terms of one or two coordinates were
included. The coefficients of the six animals were pooled for each
condition, and the significance was tested to determine its validity in
describing the blood flow distribution. In many instances,
coefficients that were significant in a single animal proved to be not
significant among the six animals. Coefficients were considered
meaningful only if the coefficients of the six animals were
significant. The present study showed values of
R2 of ~0.40, indicating that ~40% of
the variability in blood flow was attributed to spatial variations.
Significant vertical, dorsal-ventral and caudal-cranial spatial
gradients of , A,
A/, and PrO2 are summarized
in Table 2. The complete set of pooled
coefficients are given in Tables A2 and A3 (APPENDIX).
Figure 1 shows plotted vs.
vertical height (x coordinate) up the lung in the LLD and
RLD postures with and without PEEP for a representative animal.
The lines represent vs. height (x) at the
center of mass (y = z = 0), determined from the regression analysis. Figures 2,
3, and 4
are equivalent data for A,
A/, and PrO2.
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Effect of Posture Without PEEP
Regional distribution of .
As indicated by the x coefficient (a) for the
whole lung, there was a significant negative (gravity-dependent)
vertical gradient (Table 2, 0.27 and 0.42
ml · min1 · ml1 · cm1)
in that was greater in the RLD posture (0.42) than in the LLD
posture (0.27), implying that blood flow in the dependent lung was
less in the LLD than in the RLD posture.
T
in both postures (Table 1), the fraction of the
T adjusted for tissue mass to either lung did
not change with body position.
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0.60 and 0.37)
observed in the LLD posture were eliminated with body inversion to the
RLD posture. These gradients represented a 70-150% change in the
mean blood flow over the height of the lung (~15 cm) or 5-10%
cm1.
In the left lung, there was a positive dorsal-ventral gradient (0.26 and 0.18) in the LLD and RLD posture, with the ventral regions having
the greater blood flow. The dorsal-ventral gradient in the left lung
was accompanied with a negative caudal-cranial gradient in the LLD
posture (0.18), with blood flow greatest in the caudal regions.
Regional distribution of A.
For the whole lung, the largest vertical gradient in A
was observed in the RLD posture (Table 2, 0.58) and occurred in conjunction with a positive dorsal-ventral gradient (0.31) that was
eliminated with inversion to the LLD posture. In the LLD posture, the
only substantial gradient occurred in the dorsal-ventral direction (0.27).
T, total ventilation was
smaller in the dependent lung than in the nondependent lung in the LLD posture but larger in the dependent lung in the RLD posture (Table 3).
For constant ventilation in both postures, body position had no effect
on ventilation in either lung. In the left lung in the RLD posture,
significant vertical (0.20) and dorsal-ventral (0.27) gradients were observed.
Relationship between regional and total blood flow and ventilation
for each lung.
The vertical gradients in and A (Table 2)
measured in this study might appear at first sight to be at odds with
the total blood flow and ventilation values measured for each lung (Table 3). For the whole lung, the vertical gradient in in the
LLD posture would suggest a greater blood flow in the dependent lung
than in the nondependent lung (Table 2). On the other hand, the total
blood flow to the dependent left lung in the LLD posture was clearly
lower than that to the nondependent lung. This apparent discrepancy is
due to the fact that the total blood flow to the lung is the product of
the mean regional and the total lung volume. This
relationship allowed the estimate of FRC to each lung. The smallest
FRC was predicted to occur in the left lung in the LLD posture.
(Table A2) averaged 5.8 and 4.6 ml · min1 · ml1 in the left
and right lung pieces, respectively. T (3.6 l/min) was distributed 1.3 l/min (37%) to the left lung and 2.3 l/min (67%)
to the right lung (Table 3). Thus the estimated FRC was 220 ml in the
left lung and 500 ml in the right lung, resulting in a total FRC of 720 ml. This value was close to the measured value (758 ml) equal to the
air volume (645 ml, Table 1) and wet tissue volume (113 ml) based on
lung wet weight (4.7 × 24 g dry weight). The predicted left
lung FRC was 31% total FRC. The expected FRC of a uniformly inflated
left lung based on tissue mass was 43% total FRC. This value was
reduced by ~25% via the vertical Ptp gradient, resulting in a left
lung FRC of 32%, near the predicted value of 31%. Accordingly, the
reduced blood flow to the dependent left lung in the LLD posture was
consistent with a reduced FRC caused by the vertical Ptp gradient.
Evidently vertical gradients in require knowing regional lung
volume to accurately predict relative blood flow to each lung. A
similar argument applies to A measurements.
Regional distribution of PrO2 and
A/.
The largest gradient in PrO2 (1.3, Table 2) was
observed in the vertical direction for the whole lung in the LLD
posture and was positive, indicating that PrO2 was
smaller in the dependent (left) lung than in the nondependent (right)
lung (intercepts, Table A3). This vertical gradient was abolished with
inversion to the RLD posture and was accompanied with positive
dorsal-ventral and caudal-cranial gradients.
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4 cm), dorsal
(y = 5 cm), and caudal (z = 8 cm) regions of the lung (Fig. 6). The maximum value of
PrO2 (124 ± 5 Torr) was located in the
nondependent (x = +4 cm), ventral (y = +5 cm), and cranial (z = +8 cm) region of the lung. In
the RLD posture, minimum and maximum PrO2 values
evaluated at similar (x, y, z) values
used for the LLD posture were 96 ± 10 and 117 ± 8 Torr,
respectively (Fig. 6). Note that PrO2 was reduced
below 100 Torr only in the dependent lung in the LLD posture.
The low PrO2 originating from the dependent
caudal-dorsal regions of the dependent left lung in the LLD posture
without PEEP was increased by inversion to the RLD posture (Fig. 4).
That body inversion from the LLD to the RLD posture increased
PrO2 in the caudal regions was consistent with the
reduction or elimination of significant positive vertical,
dorsal-ventral, and caudal-cranial PrO2 gradients for
the whole lung (Table 2).
In the left and right lung, small but significant gradients in
PrO2 and A/ were observed in
all three coordinates (Table 2). However, the detection of a
significant A/ (PrO2)
gradient was associated with a significant PrO2
(A/) gradient only in the left dependent lung
in the LLD posture. In the left (dependent) lung in the LLD posture, a
dorsal-ventral A/ gradient (0.053) was
associated with significant PrO2 gradients (2.8).
Comparison Between Predicted and Measured Gas Exchange
Predicted PaO2 and PaCO2 calculated from regionalA/ data did not
differ from measured PaO2 and PaCO2
in both the LLD and RLD posture (Table 1), and the measured
A-aDO2 was well predicted from the microsphere
data in the LLD posture. However, the predicted values of
A-aDO2 were significantly (P < 0.05) less in the LLD than in the RLD posture (Table 1).
Mean A/ and PrO2
Changes of Nondependent and Dependent Lung
A/ was greater in the nondependent right lung
(1.42 ± 0.45) than in the dependent lung (0.93 ± 0.37). In
the right lung, PrO2 increased with body inversion
from the RLD (113 ± 7 Torr) to the LLD (119 ± 4 Torr) posture. This was associated with an increase in
A/ from 1.09 ± 0.39 in the RLD posture
to 1.40 ± 0.60 in the LLD posture. This behavior was accompanied
with a dorsal-ventral A/ gradient that was
significant (0.035) only in the RLD posture.
Regional Variations in the Spatial Gradients
The significant coefficients d, e, and f, shown in Tables A2 and A3 indicated that the spatial gradients varied along an orthogonal axis. These are discussed in the APPENDIX.Effect of PEEP
Regional distribution of .
In general, PEEP either reduced or eliminated the spatial
gradients in and A that occurred without
PEEP (Table A2). The decrease in the vertical gradient with PEEP was
associated with a decrease (30-50%) in the mean blood flow
(intercepts, Table A2). With PEEP, the dependent right lung in the RLD
posture had the greater blood flow, similar to the behavior without
PEEP (Table 3). By contrast, in the LLD posture PEEP eliminated the
left-right lung difference in blood flow measured without PEEP.
A/ gradient (from 0.053 to 0.03, Table A3)
and 50% reduction of the caudal-cranial PrO2 gradient
(from 0.85 to 0.40) in the left lung.
Similar to the data without PEEP, with PEEP PaO2 and
PaCO2 calculated from A/
data did not differ from measured PaO2 and PaCO2 in both the LLD and RLD posture, and the
measured A-aDO2 was well predicted from the
microsphere data (Table 1).
PEEP reduced the relatively high A/ of the
nondependent right lung to a value closer to 1 (Table A3, 1.22 ± 0.24). In the right lung with PEEP, A/
increased with body inversion from the RLD posture (1.13 ± 0.24)
to the LLD posture (1.22 ± 0.24).
In the left lung in the LLD posture, PEEP increased
PrO2 from 105 ± 12 to 112 ± 7 Torr (Table
A3). This behavior was associated with a PEEP-induced vertical
PrO2 gradient (0.83) in conjunction with reduced
dorsal-ventral and caudal-cranial PrO2 gradients.
Regional Perfusion Correlation Between Postures With and Without PEEP
Figure 5 shows to each
lung piece in the LLD posture plotted against blood flow of the same
piece in the RLD posture of one representative animal without PEEP
(Fig. 5A) and with PEEP (Fig. 5B). Except for the
left lung without PEEP (R = 0.66), blood flow to each piece was
poorly correlated (R = 0.044-0.22) between LLD and
RLD posture. In other words, lung pieces with high (or low) blood flow
in the LLD posture received low (or high) blood flow in the RLD
posture. This behavior was consistent with the gravity-dependent
vertical gradients observed for both right and left lungs and for the
whole lung in both postures, opposite to that found between the supine
and prone position (19).
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and A heterogeneity.
The mean coefficients of variation of and A
(30-60%) were similar to reported values (19, 21, 29,
33, 40). Table 4 summarizes the
heterogeneity in A and evaluated by three
methods: total and residual variances of A, ,
and A/; widths
(lnSDA and lnSD) of
the A-A/ and -A/ distribution curves measured by
FMS and MIGET. The variance of the data based on regional values was
similar to that based on uncorrected data. The coefficients of
correlation (c) between A and
(Pearson's method) were similar to those computed by use of
A, , and
2A/ in Eq. 8
(33). The total variance data showed that in the LLD
posture PEEP reduced the variance in A and
A/ but not in , consistent with a more
uniformly inflated lung at the higher lung volume. This PEEP-induced
change in variance was undetected by the other two methods. Neither
body position nor PEEP affected the total variance in . Neither
PEEP nor body position changed the correlation between
A and . There was a tendency for
heterogeneity measured by lnSDA and lnSD to be greater with MIGET than with FMS, but the
difference was only significant for in the LLD posture without
PEEP. The broader distribution measured with MIGET than with
topographical data has been noted in previous studies (15,
45). The difference has been attributed to the coarse scale of
the A/ distribution inherent in MIGET
(4, 5).
|
A, , and
A/ that was attributed to residual variation
as measured by the residuals of the regression analysis was reduced
from 65 ± 16% of the total variance in the linear regression
analysis to 41 ± 6% of the total variance in the fourth-order
regression analysis (Table 4). These values are in line with the
coefficients of determination (R2) of ~40 and
60% that implicated ~60 and 40% of the variability to residual
variation. Similar to the total variance, PEEP reduced the residual
variance of A in the RLD posture. Neither body position nor PEEP affected the residual variance in . There was
a tendency for PEEP to increase the residual-to-total variance fraction in A and A/, but
this was only significant in the LLD posture. The coefficient of
correlation (c) between A and
calculated by using the residual variances (0.59-0.75, Table 4) in
Eq. 8 was similar to the correlation coefficient between A and (0.57-0.71).
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
In this study we used a high-resolution technique to describe the
distribution of , A,
A/, and PrO2 in the lateral decubitus posture. The high resolution in conjunction with multiple linear regression analysis allowed the spatial description of these
variables at any arbitrary position relative to the three rectangular
coordinate axes.
The major findings of this study are as follows. First, the
gravity-dependent vertical gradient in was greater in the RLD than LLD posture (Fig. 1, A and B; Table 2). This
was attributed to a reduced blood flow in the dependent left lung in
the LLD posture (Table 3). Second, PEEP reduced the vertical gradient in both postures and eliminated the difference between postures (Fig.
1). PEEP or body inversion from the LLD to the RLD posture abolished
the positive vertical, dorsal-ventral, and caudal-cranial gradients in
PrO2 observed in the LLD posture (Table A3). Third, a
positive vertical gradient in PrO2 was observed in the
LLD posture with the dependent dorsal-caudal regions of the dependent
lung having values below that (100 Torr) needed to invoke a hypoxic vasoconstriction response (31). This behavior was
consistent with the reduced blood flow to the dependent lung in the LLD posture.
Methodological Issues
Fluorescent microsphere technique. The microsphere technique as implemented in this study has been validated in previous studies (17, 40). Regional deposition of aerosolized and injected microspheres allowed simultaneous measurements of ventilation and perfusion distribution that predicted regional gas exchange with high spatial resolution.
Volume adjustment to FRC and vertical Ptp gradient.
Injected and aerosolized fluorescent microspheres were delivered in
vivo near FRC, whereas the fluorescent signals were measured in vitro
in the dried lung inflated to TLC. Accordingly, we made several
adjustments to the weight of each piece to extrapolate to piece volume
in vivo and to determine and A per unit
regional lung volume at FRC.
by a factor of ~3, N/D in regional lung volume, and D/N in regional lung
density (16). Implicit in this adjustment for lung density
is the scaling of tissue mass to capillary density. Accordingly,
regional lung density changes caused by the vertical Ptp gradient were
the dominant contributor to the vertical gradient in and
A.
Prior studies have reported the vertical gradients of perfusion
relative to the number of alveoli or piece weight at TLC. This paper
presents perfusion gradients relative to the regional lung volume at
the time of microsphere injections. The adjustment for the vertical
changes in regional lung density produced vertical gradients in
regional that were greater than those estimated in previous
studies using TLC-measured regional volume (18, 19, 21, 22, 33,
34). These normalization issues need further evaluation,
particularly in the supine and upright body positions under both normal
and increased acceleration loads with relatively large Ptp gradients
(1, 2).
We made no adjustment for Ptp gradients in the other two axes
(y and z), in the absence of reported data. Blood
volume was ignored in the calculation of lung density and regional lung
volume because the dry weight used in the calculation of mean lung
density was blood free.
Distribution of Regional Perfusion
Effect of gravity. The effects of gravity on the vertical gradient in blood flow in the lung have been described in terms of the relation among the Ppa and pulmonary venous (Ppv) and alveolar (Palv) pressures (48, 49). This theory predicts a decreasing blood flow up the height of the lung (in our nomenclature, a negative vertical gradient). Most of the vertical gradients measured in the present study are explainable, at least qualitatively, with the gravitational model. The vertical gradients in blood flow measured in the LLD and RLD posture with and without PEEP were expected and confirmed previous findings (6, 20, 25, 28, 37).
Effect of lung volume and vascular resistance.
The fact that the gravity-dependent vertical gradients in
decreased with a change from RLD to LLD posture and with PEEP indicates
that factors other than gravity contributed to the blood flow
distribution. A major factor was the lung volume-induced vascular
resistance that changed with body position and PEEP. Pulmonary vascular
resistance depends on lung volume (24); its changes with
lung volume are different for zone 2 (Ppa > Palv > Ppv) and
zone 3 (Ppa > Ppv > Palv) conditions (9). By
this theory (24), is proportional to Ppa Palv in zone 2 and Ppa Ppv in zone 3. The increased
flow down the lung is due to Ppa increasing down the lung in zone 2 and
to Ppv-induced capillary recruitment or vascular distention in zone 3.
Palv and Ppv Palv under both zone 2 and zone 3 conditions in
isolated rabbit lungs. In zone 3, for Ppa-Palv of 18 mmHg, blood flow
increased linearly with a decrease in lung volume from TLC to residual
volume. In zone 2, blood flow increased as lung volume
decreased from TLC to 50% TLC but decreased from 60% TLC to residual
volume, a behavior consistent with the U-shape curve describing the
relationship between vascular resistance and lung volume
(44). Whatever the lung volume-induced differences in
blood flow, blood flow was greater in zone 3 than in zone 2.
In the present study, without PEEP, Ppv averaged 8.4 cmH2O
in the LLD posture and 6.1 cmH2O in the RLD posture (Table
1, Ppcw) relative to mid-heart level. With a mean Paw of 5 cmH2O (Table 1), the dependent lung was in zone 3 in both
postures whereas the nondependent lung was predominantly in zone 2, more so in the RLD than in the LLD posture. PEEP increased Ppv to 10 cmH2O and mean Paw to 15 cmH2O in both
postures, placing the nondependent lung and half of the dependent lung
in zone 2. Pulmonary vascular resistance, (Ppa Ppcw)/blood
flow, was greater in the dependent than nondependent lung in both
postures and increased with PEEP (Table 1).
The gravity-dependent vertical gradients in blood flow measured in both
postures for the whole lung without PEEP (Table 2, Fig. 1, A
and C) were consistent with the shift from zone 2 to zone 3 conditions down the lung, but these gradients were accentuated by the
threefold increase in lung density down the lung. The removal of the
density gradient with PEEP reduced the gradients to 44 and 33% in the
LLD and RLD posture, respectively (Table 2, Fig. 1, B and
D). Thus the two- to threefold increase in the gradient with
the removal of PEEP was attributed almost entirely to the lung density
gradient. A similar behavior was observed for both left and right lungs
in the LLD posture (Fig. 1, A and B).
Blood flow was lower in the dependent left lung than in the
nondependent lung (Table 3), consistent with the results of a previous
study (28). This behavior was opposite to that predicted by gravity, indicating that factors other than gravity contributed to
blood flow distribution in the LLD posture. One factor has been
associated with the vascular structure (17, 28). The reduced blood flow to the dependent left lung was not caused by a heart
weight induced lower lung volume per se because a reduced lung volume
is associated with a lower vascular resistance in zone 3 (9). It is possible that a nonuniform lung distortion due
to heart and abdominal weight might conceivably cause an increased vascular resistance. Another mechanism such as hypoxic vasoconstriction remains an alternative explanation in vivo, particularly in view of the
positive gradient in PrO2 measured (see below).
Nongravitational gradients in .
An important finding of this study relates to other nongravitational
gradients in . Specifically, in the isogravitational (y-z) plane (x = 0), a
positive dorsal-ventral gradient in occurred in the left
dependent lung in the LLD posture, with blood flow maximal in the
ventral regions (Table 2, 0.26). The smaller blood flow in the dorsal
regions was opposite to that observed in the supine dog
(10) in which the dorsal lung regions had the larger blood
flow. Thus the present measurements would not support an intrinsic
greater vascular conductance postulated for the dorsal lung regions
(10). Thus extrinsic factors such as hypoxic
vasoconstriction and lung distortion caused by the weight of the heart
and abdomen might be crucial.
observed in the left
lung in the LLD posture occurred in conjunction with a negative caudal-cranial gradient in with increasing in the
caudal region, in the absence of any gradient in the right lung. Both these gradients were abolished with PEEP, indicating a lung
volume-induced relative shift of blood flow from the ventral-caudal to
the dorsal-cranial regions.
The decrease in blood flow in the caudal-cranial direction for the
whole lung in the LLD posture is consistent with the results of
Greenleaf et al. (20) in the mechanically ventilated
anesthetized dog. This contrasts to the absence of a caudal-cranial
gradient in spontaneously breathing humans in the lateral decubitus
posture (6).
Distribution of Ventilation
Effect of posture without PEEP.
In contrast to the absence of a vertical A gradient
in the LLD posture (Table 2), total ventilation was greater in the nondependent than dependent lung in the LLD posture (Table 3). This
difference was similar to the behavior in blood flow and was most
likely due to a smaller FRC in the dependent left lung. Body inversion
from LLD to RLD posture produced a substantial negative gradient in
A (0.58) that was consistent with the greater
total ventilation measured in the right dependent lung than in the
nondependent lung. This behavior in the anesthetized dog is consistent
with results from the anesthetized human in the lateral decubitus
posture (38, 39). These results with anesthesia differed
substantially from those in awake humans, showing greater ventilation
in the dependent than nondependent lung in both the LLD and RLD posture
(7, 25, 32). The latter behavior was explained by the
vertical Ptp gradient causing a lower lung volume and greater lung
compliance in the dependent lung regions. The absence of a
caudal-cranial gradient in A in the lateral
decubitus posture in the anesthetized dog was consistent with the
results in awake humans measured by using radioactive gas inhalation
and external scintillation counters (7, 25). This behavior
was attributed to a uniform Ptp in the horizontal direction.
A gradients were observed in the left lung
in the RLD posture and in the right lung in both postures. These gradients were accentuated by the imposed vertical gradient in regional
volume. In addition, a positive dorsal-ventral gradient in
A was observed in the left lung in both postures.
The reason for this gradient was not apparent.
Effects of PEEP.
Like the blood flow distribution, PEEP reduced the difference in
between the dependent and nondependent lung in the LLD posture
(Fig. 2, A and B, Table 3), similar to the
behavior found in the anesthetized human (39) and dog
(36). The PEEP-induced change in the vertical gradient in
A in the LLD posture occurred in conjunction with
the elimination of the positive dorsal-ventral gradient in
A (Table A2). PEEP eliminated or reduced the
negative gradient in A observed for the whole lung
and left lung in the RLD posture and in the right lung in both
postures. A similar effect was observed for dorsal-ventral gradients
for the whole lung and for the left lung in both postures. Accordingly,
in general the effect of PEEP was to reduce the spatial variations in
ventilation by increasing regional lung volume to a less compliant part
of the PV curve where tidal-volume induced changes in airway resistance are minimal.
Distribution of Regional A/
A/ ratio was greater in the
nondependent lung than in the dependent lung in the LLD posture (Table
A3). There was a tendency (not significant) for this behavior to be
reversed in the RLD posture with the dependent lung having the greater A/, consistent with the results in the
anesthetized human subjected to positive airway pressure
(28). The latter result is supported by the PEEP-induced
increase in the vertical A/ gradient in the
RLD posture (Table A3). Furthermore, PEEP produced a positive vertical
gradient in A/ in the dependent lung in both
postures. By contrast, in keeping with the PEEP-induced reduction in
the spatial variation in A, PEEP eliminated or
reduced the dorsal-ventral gradient in A/
observed for the whole lung in the RLD posture and in the dependent
lung in both postures. These nongravitational gradients measured in the
anesthetized dog with PEEP were not observed in the awake human
(6).
Distribution of PrO2
A major advantage of the fluorescent microsphere technique over other techniques is the ability to measure regional values and spatial gradients in PrO2. Estimated PaO2 values, determined from a perfusion-weighted sum of PrO2, calculated by using microsphere measures of and A, were consistent with
measured PaO2 values in the anesthetized dog in the
present study, confirming similar results in the pig (4).
However, in the present study, microsphere data underestimated
A-aDO2. This might be attributed to more
heterogeneous perfusion and ventilation with the greater spatial
resolution (4).
On the basis of multiple linear regression analysis of the PrO2 data and the calculated spatial gradients, PrO2 in the LLD posture was greater in the nondependent ventral and cranial lung regions than in the dependent dorsal and caudal lung regions, respectively. These differences were either eliminated or reduced with PEEP.
In the left lung in the LLD posture, PEEP increased
PrO2 from a mean value of 106 ± 11 to 112 ± 7 Torr (Table A3). This was accompanied with a PEEP-induced
reduction of significant dorsal-ventral and caudal-cranial
PrO2 gradients (Table A3). Accordingly, the dependent
lung in the LLD posture without PEEP had the lowest A/ (Table A3) and the lowest
PrO2. Inversion of the dependent lung to the
nondependent position and PEEP both served to increase A/ and PrO2.
In general, the PrO2 distribution was less uniform in the left lung than in the right lung, especially in the dependent LLD posture, and PEEP produced a more uniform PrO2 distribution in the dependent left lung. Compared with the dependent right lung in RLD position, the greater lung distortion caused by the weight of the heart and abdomen acting on the smaller dependent left lung in the LLD posture might contribute to a less uniform PrO2 distribution.
Hypoxic Pulmonary Vasoconstriction and Zone 4
Many studies (19, 20, 24, 26, 36) have demonstrated that blood flow decreased in the most dependent lung regions (zone 4), opposite to the behavior predicted from the effects of gravity in zone 3 (49). This behavior has been attributed to increased vascular resistance caused by hypoxic pulmonary vasoconstriction (19, 20, 26, 36) or reduced vascular diameter in the most dependent lung regions (19, 20, 26, 36). The latter effect was attributed either to a low lung volume or perivascular cuff formation due to increased transvascular fluid flux (24).Hypoxic pulmonary vasoconstriction might regulate regional perfusion to
match A to achieve efficient gas exchange
(30). Our estimates of A/ and
PrO2 provided evidence that this mechanism might be at
work in the left dependent lung in the LLD posture. In the present
study, some lung pieces of the dependent lung in the LLD posture showed
relatively low PrO2 values (Fig. 4, A and C) that were consistent with values
(PrO2 < 100 Torr) associated with hypoxic
pulmonary vasoconstriction (8, 12, 30). Estimates of
PrO2 from the data analysis (Fig.
6) provided evidence that in the LLD
posture hypoxic vasoconstriction occurred in the dependent lung, where
total blood flow was reduced relative to the nondependent lung (Table
3). PEEP increased both A/ and
PrO2 in the dependent left lung (Figs. 3 and 4) and
eliminated the hypoxic vasoconstriction, resulting in a gravity
dependent greater blood flow in the dependent lung than in the
nondependent lung.
|
Effect of Heart and Abdominal Weight on Blood Flow Distribution
Many studies (3, 23, 35, 38, 41) have suggested that lung volume and blood flow of the dependent lung are reduced in the lateral decubitus posture because of a mediastinal shift due to heart and abdominal weight. In the dog, the weight of the heart compressed the dependent lung regions to a greater extent in the supine than in the prone position (23). The heart weight-induced change in lung volume was greater with body inversion from LLD to RLD posture than from the prone to supine posture (35).Mean calculated by the regression analysis
indicated that the PEEP-induced reduction in regional perfusion
at the center of mass near the heart was greater in the nondependent
than in the dependent lung (Table 2, intercepts). This effect was
greater in the left than in the right lung. Thus the effect of PEEP on the blood flow distribution was greater in the left lung in the LLD
posture than in the right lung in the RLD posture. The difference in
the preinspiratory lung volume between the left and right lung may be
involved, in view of studies in anesthetized humans (38) showing that FRC of the right lung in the RLD posture was larger than
FRC of left lung in the LLD posture, whereas FRC of the nondependent right lung was similar to the dependent right lung in the RLD posture.
Thus the PEEP-induced lung expansion might be greater in the right
dependent lung than in the left dependent lung that was closer to its
closing volume. The reduced effect of PEEP in the left dependent lung
in the LLD posture might be exacerbated during anesthesia, which might
reduce diaphragmatic tone and reduce the diaphragmatic support of
abdominal weight (14, 41). Thus the nonuniform ventilation
distribution observed in the LLD posture can be alleviated by inversion
to the RLD or with PEEP.
and A Heterogeneity
and A heterogeneity in this study
as measured by the coefficient of variation of and
A (30-60%) is consistent with previous studies
using fluorescent microspheres (18, 19, 21, 29, 33, 34,
40). However, on the basis of a one-dimensional linear
regression analysis, the latter studies concluded that ~90% of the
heterogeneity in was due to factors other than spatial
variation. By contrast, the multiple regression analysis in the present
study indicated that ~40% of the variability in ,
A, and A/ distributions
was attributed to spatial variation (Table 4). The contribution (60%)
by the residual variance in the distribution is near to that
measured in the supine dog (11).
The factors that contributed to the residual variance include
heterogeneity on a scale that was smaller than ~1 cm, the dimension of the lung cube in which and A were
measured (50). The variances of A,
, and A/ attributed to residual
variation produced a correlation between A and
similar to that produced by the total variability (~0.65).
This behavior in conjunction with the 40% of the total variance in
A/ attributed to residual variability
suggests that matching of A and is not
predominantly associated with random variability. The relative
contribution of residual variability using multiple regression analysis
in previous studies (18, 19, 21, 22, 29, 33, 34, 40) needs
further evaluation.
In conclusion, blood flow to the dependent left lung in the LLD posture was lower than that expected because of gravity. The reduced blood flow resulted from hypoxic vasoconstriction that occurred because of a reduced ventilation to the dependent lung compressed by the mediastinal contents. These effects were abolished with 10 cmH2O PEEP and inversion to the RLD posture.
| |
APPENDIX |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
Table A1 summarizes the
x, y, and z coordinate distances (cm)
of the center of mass of left, right, and whole lung, relatively to the
original coordinate axes (x0,
y0, z0) oriented at the
edges of the lung. As lung volume increased with PEEP, the coordinate distances between the center of mass and original coordinate axes increased. The increase in distance was greatest (~50%) in the LLD
posture and least (~10%) in the RLD posture.
|
Regional Variation in the Spatial Gradients
The coefficients d-f of the independent variable xy, yz, and zx in the linear equation (Eq. 5) are measures of the variation of the spatial gradients in any one coordinate along an orthogonal coordinate (Tables A2 and A3). For the whole lung without PEEP in the LLD posture, the vertical gradient (
/x) in blood flow increased linearly with
z (coefficient f, 0.046)
|
(A1) |
0.59
· ml1 · cm1 in the
caudal region at z = 7 cm to a value of 0.05 in the
cranial regions at z = 7 cm. Thus the vertical gradient
was maximal in the caudal regions and vanished in the cranial regions.
The application of PEEP reduced this z variation of the
vertical gradient to 9% (coefficient f, 0.005).
|
|
Similarly, taking the left lung separately in the LLD posture, the
significant coefficient e (0.074, Table 2) implies that the dorsal-ventral gradient in also varied linearly with
z (x = 0)
|
(A2) |
0.26 in the
cranial regions (z = 7 cm) and became positive (0.78)
in the caudal regions (z = 7 cm). Similar variations
in other spatial gradients were present for both and
A. Variations in the gradients in
A were substantial only in the LLD posture without PEEP.
| |
ACKNOWLEDGEMENTS |
|---|
We thank Bill Altemeier and Wayne Lamm for helpful suggestions and criticism and Ian Starr, Jenny Souders, Erin Shade, Dowon An, Shen Sheng Wang, and Emily Anderson for excellent technical assistance.
| |
FOOTNOTES |
|---|
This research was supported by National Heart, Lung, and Blood Institute Grant HL-12174, a fellowship (to H. Chang) from the Tri-Service General Hospital at Taiwan, and a sabbatical leave (S. J. Lai-Fook) from the University of Kentucky.
Address for reprint requests and other correspondence: M. P. Hlastala, Div. of Pulmonary and Critical Care Medicine, Box 356522, Univ. of Washington, Seattle, WA 98195-6522 (E-mail: hlastala{at}u.washington.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.
10.1152/japplphysiol.00377.2001
Received 20 April 2001; accepted in final form 17 September 2001.
| |
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DISCUSSION
APPENDIX
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); L, left lung (
). Lines represent
best-fit values from multiple linear regression analysis.
R2 indicated that ~40% of the variability in
blood flow was spatially determined. WL, whole lung; RL, right lung;
LL, left lung. Independent and dependent axes have been interchanged
for presentation.
