Vol. 88, Issue 3, 1076-1083, March 2000
Regional ventilation-perfusion distribution is more uniform in
the prone position
Margareta
Mure1,
Karen B.
Domino2,
Sten G. E.
Lindahl1,
Michael P.
Hlastala3,
William
A.
Altemeier3, and
Robb W.
Glenny3
1 Department of Anesthesiology and Intensive
Care, Karolinska Hospital and Institute, SE-171 76 Stockholm,
Sweden; and Departments of 2 Anesthesiology
and 3 Medicine and Physiology and Biophysics,
University of Washington School of Medicine, Seattle, Washington 98195
 |
ABSTRACT |
The arterial blood
PO2 is increased in the prone
position in animals and humans because of an improvement in ventilation (
A) and perfusion
(
) matching. However, the mechanism of improved A/ is unknown. This
experiment measured regional
A/ heterogeneity and the correlation between A and
in supine and prone positions in pigs. Eight
ketamine-diazepam-anesthetized, mechanically ventilated pigs were
studied in supine and prone positions in random order. Regional
A and were
measured using fluorescent-labeled aerosols and radioactive-labeled
microspheres, respectively. The lungs were dried at total lung capacity
and cubed into 603-967 small (~1.7-cm3) pieces. In
the prone position the homogeneity of the ventilation distribution
increased (P = 0.030) and the correlation between A and increased
(correlation coefficient = 0.72 ± 0.08 and 0.82 ± 0.06 in supine
and prone positions, respectively, P = 0.03). The homogeneity
of the A/
distribution increased in the prone position (P = 0.028). We
conclude that the improvement in
A/ matching in the
prone position is secondary to increased homogeneity of the
A distribution and increased
correlation of regional A and
.
aerosol; fluorescent microspheres; pulmonary blood flow-ventilation
heterogeneity
| |
INTRODUCTION |
ARTERIAL BLOOD OXYGENATION is often improved in the
prone position in animals and humans with normal and injured lungs (1, 8, 10, 14, 16, 18-20, 31). The prone position improves oxygenation
by improving ventilation-perfusion
(A/) matching, as
measured by the multiple inert gas elimination technique (MIGET) (1, 8,
18). Using single-photon emission-computed tomography, Lamm et al. (14)
found that the prone posture decreased
A/ heterogeneity in
dogs with normal and oleic acid-injured lungs. However, the mechanism
of the decreased A/
heterogeneity in the prone position is unclear. If
A and distributions
can be characterized as normal distributions in the logarithmic domain, the expected variance in
A/ can be described by
A, , and the
correlation between them. Using this relationship, Wilson and Beck (33)
postulated that the
A/
distribution is more uniform in the prone than in the supine posture
primarily because of more uniform distributions in
A and in the prone
posture. They assumed that the correlation between
A and was less in the
prone position but that this had little impact on the
A/ distribution because
of the uniformity in A and
. The present experiment is the first to measure
regional A/
distributions and correlation of regional
A and in the supine
and prone position, thus directly testing the model of Wilson and Beck.
| |
METHODS |
This study represents a further analysis of data collected from seven
of eight animals by Mure et al. (18), which described the influence of
abdominal distension and position on pulmonary gas exchange by use of
the MIGET. One additional animal was added to the present study. Only
data from the control conditions are analyzed in this study, and
regional A/
distribution data were not analyzed as part of the original study.
Animal preparation and experimental protocol.
The study was approved by the University of Washington Animal Care
Committee. The animal preparation and experimental protocol were
described in detail in the earlier publication (18). Briefly, the
investigation was performed in eight 30- to 45-day-old pigs [15.4 ± 2.0 (SD) kg body wt (range 13-20 kg)]. The pigs were
healthy and free from significant diseases. The pigs were allowed to
eat and drink ad libitum until premedication, which consisted of an intramuscular injection of xylazine (2 mg/kg) and ketamine (20 mg/kg)
given 10 min before the start of the investigation. Anesthesia was
induced with ketamine (20 mg/kg iv) and diazepam (0.5 mg/kg iv) and
continued with a mixture of diazepam (1.7 mg/ml) and ketamine (67 mg/ml) at 4 ml/h. Anesthetic agents for maintenance were given in
sufficient doses to prevent spontaneous ventilatory effort and to
maintain a surgical plane of anesthesia. No muscle relaxants were used.
After tracheotomy and endotracheal tube insertion, all pigs were
mechanically ventilated with a fractional inspiratory O2 of
0.4 and a tidal volume of 15 ml/kg at a respiratory rate to achieve
normocapnia. Body temperature was adjusted to normal with heating pads.
One arterial catheter was inserted into the carotid artery to monitor
mean systemic blood pressure and heart rate and another into the
femoral artery for blood-gas sampling (model ABL 4, Radiometer, Copenhagen, Denmark). A 5-F pulmonary artery catheter was inserted via
the internal jugular vein to measure body temperature and cardiac
output in triplicate (Edward's COM 2, Baxter, Irvine, CA). Pulmonary
arterial pressure and pulmonary capillary wedge pressure were recorded.
Both femoral veins were catheterized. One vein was used for infusion of
six inert gases, of which acetone was analyzed in a gas chromatograph
(Varian 300, Walnut Creek, CA) to determine anatomic dead space (9,
30). Microspheres and maintenance fluids were administered via the
second femoral venous catheter.
All pigs were studied in prone and supine positions in random order. In
the prone position the pigs rested on their abdomen. After a period of
30 min to achieve steady-state conditions, the first series of
measurements were obtained. The animals were allowed to stabilize in
the other position for 30 min before the next sets of measurements.
Measurements of regional A and
distributions.
Regional A was measured using inhaled
aerosolized fluorescent (blue-green, yellow-green, orange, and red)
microspheres (26) with a particle size of 1.0 µm (FluoSpheres,
Molecular Probes, Eugene, OR). Simultaneously with the inhaled
microspheres, regional was measured by injection
of radioactive (113Sn, 103Ru, 95Nb,
and 46Sc) microspheres (10) with a particle size of 15 µm
(Dupont NEN Research Products, Boston, MA).
After the last measurement, heparin (10,000 U iv) and papaverine (60 mg
iv) were administered, and the animals were exsanguinated while saline
was freely infused intravenously. The lungs were harvested and perfused
with a dextran solution. The lungs were visually inflated to total lung
capacity and air-dried for 3 days at transpulmonary pressure of 25 cmH2O. The lobes were glued in their anatomic position with
cyanoacrylate glue (Duro Superglue, Locite, Cleveland, OH).
The dried lungs were coated with a cold setting foam and then encased
in rapidly setting isocyanate foam (2 lb Polyol Isocyanate, International Sales, Seattle, WA). A miter box was used to cut the
lungs into ~1.7-cm3 cubes. Any foam adhering to the lung
piece was removed, and the pieces were weighed. Pieces weighing <8.0
mg were discarded. Each lung piece was assigned a unique
three-dimensional (x, y, z) coordinate, where x
represents distance in the right-to-left plane, y represents distance in the dorsal-to-ventral plane, and z represents
distance in the caudal-to-cranial plane.
Piece radioactivity was read in a gamma counter (Minaxi gamma counter
system, model 5550, Packard, Downers Grove, IL). Each piece was soaked
for 48 h in 1.5 ml of 2-ethoxyethyl acetate (Cellosolve, Aldrich
Chemical, Milwaukee, WI) to extract the fluorescent markers. The
extract was transferred into a cuvette, and the fluorescent intensities
of each color were measured in a fluorescent spectrophotometer (model
LS 50B, Perkin-Elmer, Norwalk, CT).
Calculations.
The data were treated in four different fashions depending on the
analysis. Linear gradients and coefficient of variation of
A and
distributions were determined in milliliters per minute. Natural
logarithm (ln) transformations of A and
data were used to calculate variances and the
correlation coefficient as postulated by Wilson and Beck (33). A
logarithmic (log) transformation of
A/ ratios was used
to assess linear gradients in the
A/ distribution.
Flow- and ventilation-weighted
A/ distributions were calculated from the microsphere-derived
A/ distributions and were compared with those derived by MIGET in the traditional log domain.
Ventilation to each lung piece (ml/min) was calculated as follows
|
(1)
|
Perfusion
to each lung piece (ml/min) was calculated as follows
|
(2)
|
A
to each piece was then divided by to the same
piece to obtain the
A/ ratio to each piece.
The heterogeneity of A and
was assessed by the coefficient of variation
(SD/mean) and the variance (
2) of
lnA and
ln. The coefficient of correlation (
) between A and was
calculated using the Pearson coefficient of correlation. The
heterogeneity of the
A/ distribution was
calculated directly by the variance of the
lnA/
(
and indirectly using an equation derived by Wilson and Beck (33) (
), where A/,
A, and are
measured in the ln domain according to the following equation
|
(3)
|
Slopes in A,
, and log
A/ distributions
were characterized as a linear function of distance in centimeters in
the dorsal-to-ventral (y) and caudal-to-cranial (z)
spatial vectors by using least-squares regression analysis. Although
somewhat of an oversimplification, a linear slope is an easily
understood method to describe a general trend in the data. To assess
the gravitational (y) gradient within a transverse section, new
slopes of A,
, and log
A/ in the
dorsal-to-ventral direction were recalculated after correction for
trends in the caudal-to-cranial (z) direction (32).
Because MIGET relies on whole lung inert gas exchange to determine the
A/ distribution, it
cannot directly measure discrete regional
A/ compartments.
Instead, MIGET calculates the amount of blood flow and ventilation to
50 A/ compartments
evenly distributed along a logarithmic axis between 0.0005 and 1,000. The MIGET software then calculates a perfusion- or ventilation-weighted mean and standard deviation of this
A/ distribution
(log SD and log
SDA,
respectively). In contrast, the microsphere method measures
A, , and
therefore A/ to
many discrete compartments. To compare microsphere-measured data with
MIGET results, the
A/ data
measured with microspheres must be weighted in a manner analogous to
that used by MIGET. The mean of the perfusion-weighted
A/ distribution
(
) is calculated as
follows
|
(4)
|
where
i and
i are the blood flow and
ventilation, respectively, to piece i of n pieces and
ln is the natural logarithm of the
A/ ratio. The
standard deviation of the perfusion-weighted
A/ distribution
(log SD) is calculated by
|
(5)
|
The
mean of the ventilation-weighted
A/ distribution
(
A) and the standard deviation
of the ventilation-weighted
A/ distribution
(log SDA) are calculated in a
similar manner.
From these data, standard deviations of
A and
distributions with reference to log
A/ (log
SDA and log
SD, respectively) were calculated (3). Log
SDA reflects heterogeneity in the
A distribution with reference to
A/. Log
SD reflects heterogeneity in the
distribution with reference to
A/. These
values are therefore similar in concept to log
SDA and log
SD derived from MIGET (9, 30).
Statistics.
Slopes of linear gradients from all animals were compared with zero
with a single-sample two-tailed t-test. Differences in all
heterogeneity data and flow gradients from all animals were compared in
supine and prone positions by two-tailed paired t-tests. Differences in the correlation coefficient were compared using Fisher's z transformation. P < 0.05 was considered
statistically significant. Values are means ± SD.
| |
RESULTS |
Hemodynamics and respiratory variables are presented in Table
1. Arterial
PO2
(PaO2) increased and alveolar-arterial PO2 difference decreased in the prone
position (P = 0.03). Otherwise, there were no differences in
these variables between the supine and prone positions.
The number of lung pieces analyzed per animal ranged between 603 and
967 pieces, with 12-14 right-to-left planes, 10-13
dorsal-to-ventral planes, and 16-21 caudal-to-cranial planes.
There was considerable isogravitational heterogeneity of the
A and distributions (Fig. 1). The coefficient of variation of
A was decreased in the prone compared
with the supine position (P = 0.012; Table 2). Although the coefficient of variation
of decreased, it was not statistically significant
(P = 0.11; Table 2). A was increased in ventral regions in both positions (Fig. 1), as reflected by dorsal-to-ventral (vertical) gradients greater than zero
(Table 2). A was increased in
the cranial compared with the caudal regions in the supine position
(P = 0.01; Table 2). The vertical gradient in
A in the supine position remained after
correction for trends in the caudal-to-cranial dimension (Table 2). The magnitude of the caudal-to-cranial gradient in
A decreased (P = 0.03) in the
prone position (Table 2). tended to be increased in
dorsal and cranial regions in the supine position (Fig. 1), although
the dorsal-to-ventral (vertical) and caudal-to-cranial gradients were
not significantly different from zero (P = 0.18 and P = 0.15, respectively). However, the vertical gradient in became significantly different from zero in the
supine position, after correction for trends in the caudal-to-cranial
dimension (P = 0.004; Table 2). In contrast, there were no
vertical or caudal-to-cranial gradients in the
distribution in the prone position. A and
tended to decrease in the peripheral lung regions
(Fig. 1), but when normalized by piece weight and mean ventilation or flow, respectively, this trend was not observed.
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Fig. 1.
Ventilation (A; A) and perfusion
(; B) as a function of dorsal-to-ventral
distance in supine and prone position in a representative pig.
Independent and dependent axes have been interchanged for presentation.
A and are plotted for
each lung piece at each plane in dorsal-to-ventral (y)
directions. Solid line, linear regression equation. Drawings of lungs
serve as schematics to signify position of pig and are not accurate
representations of lung shape. Linear regression equations for
A vs. dorsal-to-ventral distance:
A = 0.43 (cm of lung) + 2.18 (r = 0.31) in supine position and
A = 0.27 (cm of lung) + 2.29 (r = 0.25) in prone position. A in ventral
lung regions was increased in both positions, although considerable
isogravitational A
heterogeneity was present. Linear regression equations for
vs. dorsal-to-ventral distance: =  0.2 (cm of lung) + 4.44 (r = 0.21) in supine position
and = 0.1 (cm of lung) + 2.22 (r = 0.13) in
prone position. In supine position, tended to be
higher dorsally, although there was considerable isogravitational
heterogeneity.
|
|
The A/ distribution
also had significant isogravitational heterogeneity; however,
A/ ratios became more
uniform when the animals were prone (Fig.
2, Table 2). In the supine position there
were significant dorsal-to-ventral (P = 0.002) and
caudal-to-cranial gradients (P = 0.004) in log
A/ (Fig. 2, Table 2),
such that A was relatively increased
compared with in ventral and cranial lung regions
(Fig. 2, Table 2). The vertical gradient remained after correction of
trends in the caudal-to-cranial direction (P < 0.001). In
contrast, there was no dorsal-to-ventral (vertical) gradient of log
A/ in the
prone position (Fig. 2, Table 2). The vertical gradient and
caudal-to-cranial gradients of log
A/ decreased in the
prone compared with the supine position (P = 0.002 and
P = 0.005, respectively; Table 2).
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Fig. 2.
Log A/ as a function of
dorsal-to-ventral (y) distance in supine (A) and prone
(B) position in same pig used in Fig. 1. Independent and
dependent axes have been interchanged for presentation. Linear
regression equations: log
A/ = 0.14 (cm of lung) 0.6 (r = 0.64) in supine position and
A/ = 0.01 (cm of
lung) + 0.31 (r = 0.07) in prone position. In supine position,
log A/ was lower in
dorsal and higher in ventral lung regions. Distribution of
A/ was more uniform in
prone position, although considerable isogravitational heterogeneity
remained.
|
|
The heterogeneity of the A distribution,
measured by
,
decreased in the prone position (P = 0.03; Table
3). In contrast, the heterogeneity of
the distribution, measured by
, did not change
significantly (P = 0.18; Table 3).
Correlation between regional A and
increased in the prone position ( = 0.82 ± 0.06 and 0.72 ± 0.08 in prone and supine positions,
respectively, P = 0.03; Fig.
3, Table 3).
A/ heterogeneity, as
measured by
, decreased in the prone position (P = 0.028;
Table 3). The variable of
calculated indirectly by Wilson and Beck (33),
, was identical to the observed variance of
A/
(
; Table 3).
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Fig. 3.
A as a function of in
each individual lung piece plotted according to method of Altemeier et
al. (3) in same pig used in Figs. 1-2 (A is supine,
B is prone). Regional A and
are highly correlated in both positions, although
correlation between A and
is higher in prone position.
|
|
When the heterogeneity of the A and
distributions was compared with reference to log
A/ ratios (Table
4), calculated according to Altemeier et
al. (3), the prone position was associated with a lower log
SDA (P = 0.010) and log
SD (P = 0.015). The heterogeneity of
A/
distribution, measured by log
SDA/, was also lower in
the prone position (P = 0.016; Table 4).
| |
DISCUSSION |
The major finding of this study is that
A/ distribution became
more uniform in the prone position because of an increase in
homogeneity of the A distribution and an
increase in correlation between regional
A and .
Methodological issues.
Before discussing the significance of these findings, we have to
consider the limitations of the methods used. The lungs were dried ex
vivo at total lung capacity, giving all alveoli uniform size. To
estimate regional blood flow reliably, the radioactive microspheres
need to be totally trapped by the pulmonary microcirculation. Microspheres with a 15-µm diameter are almost completely entrapped by
the pulmonary circulation (25) and adequately reflect the distribution
of blood flow (6, 16). Studies comparing the distribution of
N,N,N'-trimethyl-N[2-hydroxy-3-methyl-5-iodobenzyl]1,3-propanediamine, a diamine with a near-complete first-pass extraction by the lungs, have
shown that the principle used in the present study reflects regional
pulmonary blood flow (16).
With use of similar reasoning, instead of radioactive microspheres for
calculation of lung perfusion, aerosolized fluorescent microspheres
were used to measure ventilation. The fluorescent signals were recently
shown by Robertson et al. (26) and Melsom et al. (17) to represent
A. We therefore employed the method described by Altemeier et al. (3) to simultaneously measure regional
A and in
1.7-cm3 cubes of lung with microsphere techniques.
Because the lungs in this study were dissected along an orthogonal
grid, peripheral lung pieces are not full cubes. Hence, all the lung
pieces used in this study are not uniform in volume. We used weight
normalization in the past to correct for this artifact. We have chosen
not to weight normalize flows in this analysis, because we believe that
respiratory and inert gas exchange is determined by the relationship
between local ventilation and perfusion and their flow rates in
milliliters per minute. The additional variability in lung piece size
adds to the observed heterogeneity of A
and . The values of A
and heterogeneity in Table 2 are therefore
significantly larger than previously reported. Because this increased
variability occurs in supine and prone postures, the relative
differences between the postures remain similar to those presented
without use of weight-normalized flows, and the conclusions of the
study are unchanged. The correlation between local ventilation and
perfusion is also slightly increased: small pieces tend to have less
ventilation and perfusion, whereas larger pieces have greater
ventilation and perfusion. Although directional gradients in
ventilation and perfusion are presented in milliliters per minute per
centimeter, we also explored the spatial distributions of
A and after weight
normalization. There were no significant differences in the directional
gradients between weight-normalized flows and flows in milliliters per minute.
Spatial distributions of
A/.
During mechanical ventilation, we found that
A was increased to ventral lung regions
in the supine and prone positions, as demonstrated by significant
dorsal-to-ventral (vertical) gradients (Fig. 1, Table 2). Increased
A to dependent ventral lung in the prone
position has been demonstrated previously in humans (5, 12, 23) and
animals (14). Our results are different from those in supine
unanesthetized, spontaneously breathing humans, in whom
A was increased to dorsal, dependent lung
(5, 12, 22, 24). The variations may reflect differences between the mechanical and spontaneous ventilation, species differences, and methodological factors, such as use of aerosols vs. radioactive-labeled gases, spatial resolution, and the lung volume at which ventilation was
normalized. The role of anesthesia and mechanical ventilation is likely
to be quite significant, inasmuch as it reduced the gravitational
gradient of A in supine humans by
increasing ventilation of nondependent ventral lung (24).
The increase in to dorsal lung regions in the supine
position (Fig. 1, Table 2) is consistent with prior work in humans (4,
12, 15, 21) and animals (7, 10, 17, 31). Our findings of a lack of a
vertical gradient of in the prone position (Fig. 1,
Table 2) are similar to prior results in animals with use of similar
methodology (10, 31, 32). Beck and Rehder (7) demonstrated a higher
conductance for blood flow in dorsal lung regions in the dog, which may
result in a relative increase in to dorsal lung
regions in quadruped animals independent of position (7, 10, 31).
Our study found vertical and caudal-to-cranial gradients in the
A/ distributions in the
supine position, such that
A/ ratios were lower in
dorsal and caudal lung regions than in ventral and cranial regions
(Fig. 2, Table 2). In the prone position the distribution of
A/ was more
uniform, reflected by a lack of vertical and caudal-to-cranial
gradients. Although our results are consistent with those in
anesthetized, mechanically ventilated animals (14), studies in
unanesthetized, spontaneously ventilating humans have demonstrated a
gravitational dependence of
A/, such that
A/ is increased in
dependent lung in supine and prone positions (12, 22). However, the
presence of anesthesia and mechanical ventilation may reverse this
relationship and increase A/ to nondependent
lung, as shown by Landmark et al. (15). This finding is in agreement
with that in the present series when the animals were in the supine
position. The more uniform distribution of
A/ in the prone
position contributes to the well-matched A/ in that posture and
constitutes the primary mechanism for increases in
PaO2 (1, 8, 10, 18, 19) and improvements in pulmonary gas exchange reported in the prone position (8, 14, 18).
Heterogeneity of A/.
The prone position increased homogeneity of the
A/ distribution as a
result of increased homogeneity of the A
distribution and increased correlation between regional
A and . Improvement in
the uniformity of the A
distribution is consistent with studies that suggest a more even
distribution of A in the prone position (1, 5, 14). This speaks against a marked overventilation in
nondependent regions, as we observed in the supine position. A may be more uniform in the prone
position, because the pleural pressure gradient is more uniform,
inasmuch as there is less change in pleural pressure per centimeter of
distance (20, 34). Although heterogeneity did not
change significantly with the prone position in our study with pigs,
increases in the homogeneity of the distribution
have been demonstrated in the prone position in dogs (8, 10), sheep
(31), and humans (21). The lack of change in the present study probably
reflects inadequate power due to interanimal variability, although
methodological differences and species differences [intensity of
the hypoxic pulmonary vasoconstrictor (HPV) response] may be
important. The more intense HPV response in pigs (13) may attenuate
position-related differences in heterogeneity.
The present study uniquely demonstrates an improvement in the
correlation of regional A and
in the prone position.
Wilson and Beck (33) speculated that the prone position decreases
A/ heterogeneity by
improved homogeneity of the A and
distributions. They postulated that the
A distribution was more uniform in the
prone position, because there is no gravitationally related pleural
pressure gradient. On the basis of studies in the dog, they estimated
that two-thirds of the variance in
A/ is a result of
nonuniform and one-third is the result of nonuniform A. Wilson and Beck reasoned that regional
A and must be weakly
correlated in the prone position, because
A and do not share a
gravitational influence. Although the scale of measurement (1.7 cm3) used in the present study is considerably larger than
some of the data used by Wilson and Beck, their model is not scale
dependent. The variance we observed in the distribution of
A/
(
) exactly equaled the variance in
A/ predicted by the
their model
() in both positions (Table 3). However, the magnitude of the
variance was considerably larger (Table 3) than was estimated by Wilson and Beck. In addition, the variance of regional
A was larger than the variance
of regional , in contrast to the prediction for dogs
(33). This difference in results may be due to species differences,
scale of measurement, or comparability of techniques used to measure
regional A and
. Dogs, which have extensive collateral ventilation
(13), may have a more homogeneous distribution of ventilation than
pigs. In addition, ventilation in 1.7-cm3 lung pieces is
primarily dependent on convective gas movement, whereas in smaller
units of measurement, gas diffusion dominates. Wilson and Beck also
relied on different methods to measure regional A (e.g., parenchymal density, external
detectors) and (e.g., microspheres).
A high correlation between regional A and
, as was demonstrated in the present study, has also
been observed using identical methodology in the prone pig (26).
Although counter to the prediction of Wilson and Beck (33), an
excellent correlation of regional A/ is not surprising
because of the importance of anatomic structure in determining regional
(10), and probably
A, and physiological
mechanisms, such as HPV and collateral ventilation, which act to
improve A/
matching on the local level. It is possible, however, that
A and correlation may
be lower when a smaller scale of measurement is used.
Relationship with MIGET-derived indexes of heterogeneity.
The microsphere method has an advantage over traditional measurements
of gas exchange, in that it provides spatial measurements of regional
A, , and
A/. However,
microsphere-measured data may be compared with data from more
traditional methods, such as MIGET with appropriate transformation. In
these experiments, log SD and log
SDA calculated from the microsphere
data were less than the previously reported results using MIGET (18).
This represents an underestimation of
A/ heterogeneity by
microspheres or an overestimation by MIGET. The microsphere method may
potentially underestimate true A/ heterogeneity
because of its resolution limit of 1.7 cm3. Observed
heterogeneity of regional perfusion increases in a predictable fashion
as resolution increases (11). Similarly, the observed heterogeneity of
ventilation increases as resolution improves at least to and likely
beyond the resolution obtained in this study (2, 27). Given the
relationship between the variances of the
A/, ,
and A distributions defined by Eq. 4, improved resolution will increase the observed heterogeneity of
the A/ distribution,
unless the regional correlation between A
and increases. Alternatively, MIGET may overestimate
the true A/
heterogeneity because of airway excretion of highly soluble gases
(28, 29) or because of enforced smoothing of the
A/ distribution. This
effectively limits how different and
A data points can be assigned to
compartments with similar A/ ratios.
Altemeier et al. (3) found that measurement of regional
A/ with microspheres
more accurately predicted PaO2 and
arterial PCO2 than MIGET in normal
lungs, although microspheres underestimated areas with low
A/ ratios after
administration of glass emboli (3). The correlation between
measured (by MIGET) and predicted (by microspheres) inert gas retention
was high (r = 0.99) in normal lungs (3). These results
suggest that, in the normal lung, analysis of regional
A/ with
aerosolized and injected microspheres is a valid method to study
pulmonary gas exchange and has the advantage of providing high spatial
resolution (3).
Although PaO2 increased in the prone
position in the present study, MIGET indexes, including log
SD, log SDA,
and the arterial-alveolar difference area, were not significantly
different with control conditions (18). In contrast, we observed
significant decreases in log SDA,
log SD, and log
SDA/ derived
simultaneously using microspheres. The lack of sensitivity of MIGET to
detect small, but physiologically significant, changes in
A/ heterogeneity in the
normal lung may be the result of errors induced by MIGET algorithms and
smoothing procedures and/or airway excretion of highly soluble gases
(29). Comparison of gas exchange data derived from microspheres in this
study to the gas- exchange indexes measured by MIGET (18) suggests that
the microsphere technique may possess greater sensitivity to detect changes in A/ in the
normal lung.
The present study nicely illustrates that changes in log
SD, as obtained using MIGET, do not necessarily
mean that regional changes. Inasmuch as log
SD reflects the variance of the
distribution with reference to the
A/ ratio, a change in
the A distribution and/or correlation of
A and will change log
SD, even if the distribution
is unchanged. A similar reasoning applies to the
A distribution for log
SDA. Therefore, inferences about
changes in the regional A or
distributions cannot be accurately made using
MIGET-derived variables. In addition, a more homogenous
A or distribution does
not necessarily mean improved arterial blood oxygenation or decreased A/ heterogeneity. A
unique advantage of microsphere-derived A/ distributions over
MIGET is, therefore, the ability to determine the mechanism for the
change in A/ matching,
i.e., changes in regional A
distribution, regional distribution, and/or correlation of regional A
and .
In summary, the A/
distribution was more uniform in anesthetized, mechanically ventilated
pigs in the prone position. The homogeneity of the
A distribution was increased, and
correlation of A and
was improved.
| |
ACKNOWLEDGEMENTS |
The authors gratefully acknowledge the excellent secretarial
assistance of L. Hubbard-Hamacher and the expert technical help of D. An, E. Anderson, and Dr. S. Bernard in completion of the studies.
| |
FOOTNOTES |
This study was supported by National Heart, Lung, and Blood Institute
Grants HL-12174 and HL-24163, The Swedish Heart and Lung Association,
and The Swedish Society of Medicine (Carin Tryggers Minnesfond).
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. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: K. B. Domino,
Dept. of Anesthesiology, University of Washington, Box 356540, Seattle, WA 98195-6540 (E-mail:
kdomino{at}u.washington.edu).
Received 8 April 1999; accepted in final form 25 October 1999.
| |
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ABSTRACT
INTRODUCTION
