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Spatial distribution of ventilation and perfusionin anesthetized
dogs in lateral postures
HUNG CHANG,1,5 STEPHEN J. LAI-FOOK,4 KAREN B. DOMINO,3
CARMEL SCHIMMEL,2 JACK HILDEBRANDT,1,2 H. THOMAS
ROBERTSON,1,2
ROBB W. GLENNY,1,2 AND MICHAEL P. HLASTALA1,2
Departments of 1Physiology and Biophysics, 2Medicine, and
3Anesthesiology, University ofWashington, Seattle, Washington
98195; 4Center for Biomedical Engineering, University ofKentucky,
Lexington, Kentucky 40506; and 5Division of Chest Surgery,
Department of Surgery,Tri-Service General Hospital, National
Defense Medical School, Taipei, TaiwanReceived 20 April 2001;
accepted in final form 17 September 2001
Chang, Hung, Stephen J. Lai-Fook, Karen B. Domino,Carmel
Schimmel, Jack Hildebrandt, H. Thomas Robert-son, Robb W. Glenny,
and Michael P. Hlastala. Spatialdistribution of ventilation and
perfusion in anesthetized dogs inlateral postures. J Appl Physiol
92: 745762, 2002; 10.1152/japplphysiol.00377.2001.We aimed to
assess the influence oflateral decubitus postures and positive
end-expiratory pres-sure (PEEP) on the regional distribution of
ventilation andperfusion. We measured regional ventilation (VA) and
regionalblood flow (Q) in six anesthetized, mechanically ventilated
dogsin the left (LLD) and right lateral decubitus (RLD)
postureswith and without 10 cmH2O PEEP. Q was measured by use
ofintravenously injected 15-m fluorescent microspheres, and VAwas
measured by aerosolized 1-m 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 Q, VA, the ratio VA/Q, andregional PO2 (PrO2) in both
lungs. In the LLD posture, a gravity-dependent vertical gradient in
Q was observed in both lungs inconjunction with a reduced blood
flow and PrO2 to the dependentleft lung. Change from the LLD to the
RLD or 10 cmH2O PEEPincreased local VA/Q and PrO2 in the left lung
and minimizedany role of hypoxia. The greatest reduction in
individual lungvolume occurred to the left lung in the LLD posture.
We con-clude that lung distortion caused by the weight of the heart
andabdomen is greater in the LLD posture and influences both Qand
VA, and ultimately gas exchange. In this respect, thesmaller left
lung was the most susceptible to impaired gasexchange in the LLD
posture.
pulmonary gas exchange; spatial gradients; fluorescent
mi-crospheres; mediastinal shift; regional blood flow;
positiveend-expiratory pressure
STUDIES (11, 33) HAVE SUGGESTED that regional blood flow(Q) and
ventilation (VA) are more uniform in the pronecompared with the
supine posture. This was attributedto greater Q and VA to the
dorsal lung regions, offset-ting the effects of gravity. Also, the
reduction in thedependent lung volume by the weight of the
heart
might contribute to differences in regional perfusionand VA (3).
In the lateral decubitus posture, the com-pression of the dependent
lung by the heart might begreater than that in either supine or
prone posture.Furthermore, the dependent lung has a smaller
lungvolume in the left (LLD) than in the right lateraldecubitus
(RLD) posture (35), consistent with differingeffects of the heart
between the two postures.
Q increases from the nondependent to dependentlung in the
lateral decubitus posture in the human (6,25, 28) and the dog (20,
37). In addition, the intrapul-monary ventilation distribution is
altered in the lateralposture after anesthesia and mechanical
ventilation(38, 39). Impaired gas exchange after anesthesia
andmechanical ventilation has been attributed to a mis-match
between ventilation and perfusion. The relativematching of
pulmonary blood flow and ventilation dis-tribution in lateral
decubitus postures remains uncer-tain.
Positive end-expiratory pressure (PEEP) is often ap-plied to
improve arterial oxygenation during anesthe-sia with mechanical
ventilation (28, 38, 39). In thelateral posture, PEEP has been
shown to reduce thedifference in ventilation between the two lungs
(39). Inthese studies (28, 38, 39), ventilation was measured
inrelatively large regions, such as a single lobe or
lung.Accordingly, direct evidence using a high spatial reso-lution
measure of the VA distribution in the lateraldecubitus posture
after induction of anesthesia withPEEP is lacking.
We hypothesize that the distributions of VA and Qare different
between the LLD and RLD posturebecause of differences in lung
distortion caused bythe weight of the heart and abdominal
contents.PEEP reduces lung distortion due to heart weight,may
affect the smaller left dependent lung to agreater degree, and
produces a larger decrease inpulmonary vascular resistance in the
LLD posture.
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:
[email protected]).
The costs of publication of this article were defrayed in part
by thepayment of page charges. The article must therefore be
herebymarked advertisement in accordance with 18 U.S.C. Section
1734solely to indicate this fact.
J Appl Physiol 92: 745762,
2002;10.1152/japplphysiol.00377.2001.
8750-7587/02 $5.00 Copyright 2002 the American Physiological
Societyhttp://www.jap.org 745
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PEEP may increase both VA and Q to dependent lungregions,
particularly to the dependent left lung in theLLD posture.
This study examines the effect of posture and PEEPon Q,
ventilation, and gas exchange in the lateraldecubitus posture in
anesthetized, mechanically venti-lated dogs, using both aerosolized
and intravenouslyinjected fluorescent microspheres.
METHODS
Animal Preparation and Physiological Measurements
This study was approved by the University of WashingtonAnimal
Care Committee. Six healthy mongrel dogs of eithersex [22.8 2.8
(SD, n 6) kg] were anesthetized withpentobarbital sodium (48 mg/kg
iv) and maintained witha pentobarbital infusion sufficient to
achieve a surgical planeof anesthesia and eliminate spontaneous
ventilation (1017 mg kg1 h1). Dogs were mechanically ventilated
withair via tracheostomy [tidal volume (VT) of 15 ml/kg].
Therespiratory rate was adjusted to maintain arterial PCO2(PaCO2)
between 35 and 40 Torr. Minute ventilation wasmeasured with a
spirometer. Catheters were placed in onefemoral artery and both
femoral veins. A pulmonary arterycatheter was introduced into the
right external jugular veinand used for measuring cardiac output
(QT; thermal dilution)and core temperature (Tc). Systemic arterial
(Pa), pulmonaryarterial (Ppa), pulmonary capillary wedge (Ppcw),
and air-way pressure (Paw) were recorded continuously on a
datamanagement system (Western Graphic Mach 12 DMS 1000).For
determination of anatomic dead space (VD), exhaledend-tidal PCO2
was digitally sampled with an infrared CO2detector (Perkin-Elmer,
Plumsteadville, PA), and expiratoryairflow (V) was measured by
pneumotachograph. Arterialand mixed venous blood gases were
measured with an auto-mated blood-gas analyzer (ABL 300,
Radiometer, Copenha-gen, Denmark) and corrected for temperature.
Body temper-ature was maintained by using heat lamps and pads.
Study Protocol
Animals were studied in the right and left lateral decubi-tus
postures with 0 or 10 cmH2O PEEP, in random order. Thelungs were
fully inflated (3040 cmH2O) 5 min before eachexperimental
measurement to remove atelectasis. In eachtrial, we measured Pa,
Ppa, Ppcw, QT, Tc, VT, and arterialand venous blood gas composition
immediately before fluo-rescent microsphere administration. Q was
measured withintravenously injected microspheres, and VA was
measuredwith fluorescent aerosols as described below. Functional
re-sidual capacity (FRC) was measured by He dilution duringeach
experimental condition.
Multiple Inert Gas Measurements
Pulmonary gas exchange was characterized and analyzedby MIGET,
the multiple inert gas elimination technique (46,47). Distributions
of ventilation-perfusion ratio (VA/Q) wereestimated by use of a
50-compartment model (47). Inert gasshunt (QS/QT) and dead space
(VD/VT) were obtained from themodel. Data from five of six animals
are presented since oneanimal was rejected because of the presence
of technicalerrors.
Fluorescent-labeled Microsphere Technique
VA was measured in both the LLD and RLD posture withand without
PEEP by delivering aerosolized orange, orange-
red, yellow, or yellow-green 1-m-diameter fluorescent
mi-crospheres (FluoSpheres, Molecular Probes, Eugene, OR)into the
ventilator circuit during a 5-min period (40). Simul-taneously, Q
was measured by injecting blue-green, green,crimson, or red
15-m-diameter fluorescent microspheres viathe femoral venous
catheter, in five increments over the 5min. To avoid clumping,
microspheres were sonicated andvortexed before administration.
Microsphere colors were ran-domly varied across experiments.
Terminally, the animals were deeply anesthetized withpentothal
(150 mg/kg iv); then saline, heparin (20,000 units),and papaverine
(2 mg/kg) were administered. The animalswere exsanguinated via the
arterial cannula. After a mediansternotomy, the left atrium and
pulmonary artery were can-nulated, the aorta was tied off, and the
lungs were perfusedwith 2% dextran solution to remove the blood.
The lungswere removed and dried by inflation (25 cmH2O) to
totallung capacity (TLC). The pleura was pierced in several
loca-tions with a needle to facilitate drying. To maintain a
normalanatomic configuration, the apical and most ventrocaudalrims
of the left and right lungs were joined by tissue glue.
After 7 days, the dried lungs were coated with polyure-thane
foam (Kwik Foam, DAP, Dayton, OH) and placed in aplastic-lined
square box with the caudal-cranial axis of thelung parallel to the
wall of box. The box was filled with arapidly setting foam (Polyol
and isocyanate, InternationalSales, Seattle, WA). The solid block
was sliced into 1.2-cm-thick slices. With use of a miter box, the
lung slices werediced into cubes with 1.2-cm sides. Each lung piece
wasweighed and assigned x0, y0, and z0 coordinates measuredfrom the
left, dorsal, and caudal lung edges, representing theleft-right,
dorsal-ventral, and caudal-cranial axes, respec-tively. Samples
0.008 g were discarded. Fluorescent dyewas extracted by soaking
each piece in 1.5 ml 2-ethoxy ethylacetate (Cellosolve, Aldrich
Chemical, Milwaukee, WI) for 4days. Dye concentrations were
measured with an automatedluminescence spectrophotometer
(Perkin-Elmer, model LS-50B, Norwalk, CT) at the dye-specific
excitation and emissionwavelength. A matrix inversion method (42)
was used tocorrect the fluorescent signal spillover from adjacent
colors.
Data Processing
Adjusting cube dimensions from TLC back to in situ
FRCconditions. To estimate spatial gradients in blood flow
andventilation per regional lung volume at the time of micro-sphere
injection, the dimensions of each cube were adjustedfrom their TLC
measurements to estimated in vivo valuesusing previous measurements
from anesthetized dogs (20,37). In the LLD posture, the ratios of
the maximum lunglengths at FRC to those at TLC measured
radiographicallywere 0.68 (0.85 in RLD posture), 0.76, and 0.84 in
the vertical(x), dorsal-ventral (y), and caudal-cranial (z) axis,
respec-tively. Adjusted vertical heights at FRC averaged 11.1
0.9and 14.0 1.2 cm in the LLD and RLD posture, respectively,without
PEEP; and 16.4 1.5 cm for both postures withPEEP. The adjusted
dorsal-ventral and caudal-craniallengths averaged 13.1 1.1 and 23.9
2.3 cm, respectively.
A second adjustment was made for the nonuniform defor-mation
caused by the vertical gradient in transpulmonarypressure (Ptp). At
the adjusted lung height xi measured fromthe bottom of the lung,
(Ptp)i is given by
PtpiGxi (1)
where G is the vertical Ptp gradient (0.5 cmH2O/cm
height)measured in the lateral posture in the dog (1) and i refers
tothe ith piece. (Ptp)min is 0 cmH2O at the bottom of the lung
at
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xmin 0 (1) and increases linearly to (Ptp)max at the top of
thelung at xmax, where min and max refer to minimum andmaximum,
respectively. Typically, xmax at FRC was 13 cmand (Ptp)max was 6.5
cmH2O. We used the Ptp-lung volume(PV) curve of an isolated dog
lung (27) to determine thechanges in length corresponding to
different values of Ptpalong the height of the lung (xi). Lung
volume (Vi) at each xiis given by
Vi Vmin Vmax VminPtpi/Ptpmax (2)
where (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 bottomof 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 cubelength
equal to the value after the reduction from TLC toFRC (xu). The
deformed length (xi) for the ith cube at xi isassumed to vary as
V1/3, given by the PV curve, at each (Ptp)i
xi/xu Vi/Vmid1/3 (3)
Vmid equals (Vmax Vmin)/2. The cube lengths were reducedbelow
and expanded above the undeformed mid-lung height.The x positions
of the deformed cubes were obtained bysumming the deformed cube
lengths starting from the bot-tom. The y and z dimensions of all
cubes at each xi wereadjusted by multiplying the values obtained
after adjustmentfrom TLC to FRC by xi/xu (Eq. 3).
We assumed no vertical Ptp gradient in the lateral positionwith
PEEP (2). In addition, lung volume at 10 cmH2O PEEPwas 85% TLC;
thus cube length (proportional to V1/3) was
0.95 times the cube length at TLC. Accordingly, no adjust-ment
was made to the dried lung lengths at 10 cmH2O PEEP.
Volume normalization of blood flow. Fluorescent intensityof each
color microsphere representing Q or VA to each piece(cube) was
converted to units of blood flow (ml/min) by divid-ing the
fluorescence intensity of each piece by the sum of thefluorescent
intensities of all pieces and then multiplying byQT (ml/min). Q and
VA of each piece were then converted tounits of milliliters per
minute per unit regional lung volumeat FRC by dividing by its
volume (Vi). Vi at xi was calculatedfrom its dry weight Wi, mean
lung density (), and thedeformed cube length (Eq. 3)
Vi 4.7Wixi/xu3/ (4)
The term (xi/xu)3 adjusts the mean density for changesdue to the
Ptp gradient. The product of Wi and 4.7, lungwet-to-dry-weight
ratio (43), is the wet weight. Mean lungdensity at FRC was equal to
total lung wet weight (total dryweight 4.7) divided by total lung
volume at FRC (airvolume; FRC volume of tissue mass). Tissue
density was 1g/ml. The measured FRC values are summarized in Table
1.Lung dry weight averaged 10.1 0.7 and 13.6 0.95 g forthe left and
right lung, respectively. Left lung weight was24% smaller than
right lung weight. Mean lung densityaveraged 0.14 0.02 and 0.08
0.01 g/ml at FRC and 10cmH2O PEEP, respectively.
VD was obtained by using Fowlers method (13) from theplot of
exhaled CO2 concentration vs. exhaled volume. VD wasestimated by
averaging results from three consecutive con-centration-volume
plots. Total ventilation was calculated bymultiplying frequency by
VT after subtracting VD.
Table 1. Effect of position and PEEP on physiological
variables
ZEEP PEEP
LLD RLD LLD RLD
Psa, mmHg 89.89.6 81.811.1 87.910.4 7515.5Ppa, cmH2O 19.55.5
16.24.7 26.45.4 25.13.2Ppcw, cmH2O 8.62.8 6.03.9 13.04.2*
11.62.7Paw, cmH2O 9.71.2 11.31.2 20.21.7 20.81.3QT, l/min 3.71.2
3.70.7 3.70.7 3.50.8RT, cmH2O l1 min1 3.01.2 2.61.4 3.81.1
4.41.5*RL, cmH2O l1 min1 8.34.0 7.34.0 8.32.5 13.13.5*RR, cmH2O l1
min1 4.81.8 4.02.3 7.22.6 6.62.6*HR, beats/min 12919 12835 12513
12723PaO2, Torr 1118 1039 1086 11419PaCO2, Torr 364 362 393*
383A-aDO2, Torr 45 129 44 55PaO2, Torr, FMS 10311 10411 1069
1068PaCO2, Torr, FMS 354 353 373 373A-aDO2, Torr, FMS 97 74 53 52pH
7.390.05 7.330.02 7.370.03 7.340.02PvO2, Torr 48.06.9 48.05.5
47.35.4 47.05.5Hb, g/dl 10.60.8 11.20.6 9.90.7 10.82.2VT, ml 34558
34458 34168 33962VD/VT, % 32.53.4 29.25.6 33.11.6 33.24.6VE, l/min
5.91.1 5.71.1 5.90.8 5.70.5RR, breaths/min 185 174 165 174FRC, ml
625212 599215 1,009271 1,053317
Values are means SD (n 6). ZEEP, zero end-expiratory pressure;
PEEP, 10 cmH2O end-expiratory pressure; LLD, left lateraldecubitus;
RLD, right lateral decubitus; Psa, systemic arterial pressure; Ppa,
main pulmonary artery pressure; Ppcw, pulmonary capillarywedge
pressure; Paw, peak airwary pressure; QT, cardiac output; R,
pulmonary vascular resistance (Ppa Ppcw)/Q ; T, total lung; L,
leftlung; R, right lung; HR, heart rate; PaO2, arterial O2 tension;
PaCO2, arterial CO2; FMS, microsphere predicted; A-aDO2,
alveolar-arterial O2differences; PvO2, mixed venous O2 tension; Hb,
blood hemoglobin; VD/VT, Fowlers dead space; VT, tidal volume; VE,
minute ventilation; RR,respiratory rate; FRC, functional residual
capacity. *P 0.05; P 0.01; P 0.001 compared with ZEEP in the same
posture. P 0.05, compared with LLD in the same PEEP condition.
747LATERAL POSTURE AND PEEP ON VA AND Q
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Gas exchange parameters: VA/Q and PO2. The VA/Q wasused to
calculate end-capillary PO2. We used the methoddescribed by
Altemeier et al. (4) to calculate arterial PO2,PCO2,
alveolar-arterial O2 differences (A-aDO2), and regionalPO2 (PrO2)
from the measured VA and Q fluorescent intensi-ties, Hb
concentration, body temperature, and mixed venousblood gases. With
the measured VA/Q for each piece, the massbalance equations for O2,
CO2, and N2, end-capillary O2, andCO2 contents were solved to
obtain regional alveolar PO2 andPCO2 for each piece. Regional
alveolar gas tensions of eachpiece were ventilation weighted, and
end-capillary gas con-tents were perfusion weighted and summed to
yield mixedalveolar gas tension and mixed arterial gas content.
Statistical Analysis
Q and VA per unit regional lung volume were used for
allanalyses. Values were presented as means SD. A pairedt-test was
used to evaluate a difference between two groups.ANOVA was used to
evaluate differences among more thantwo groups. A P value 0.05 was
considered significant.
Spatial variations using multiple linear regression analy-sis. A
multiple linear regression model (StatView v. 5.0.1,SAS) was used
to characterize the magnitude of Q (and othervariables VA, VA/Q,
and PrO2) as a linear function of therectangular coordinates, x
[vertical height in the left (orright) lateral posture,
left-to-right (or right-to-left) direction],y (dorsal-ventral
direction), and z (caudal-cranial direction)
Q I ax by cz dxy eyz fzx gxyz (5)
We subtracted the distances of the center of mass in the x,
y,and z directions from the original coordinate system used
forlocating each lung cube to describe blood flow in relation tothe
center of mass (x y z 0). The x, y, z coordinatedistances of the
center of mass of left, right, and whole lung,relatively to the
original coordinate axes (x0, y0, z0) aresummarized in the
APPENDIX. The intercept (I) represents themean blood flow at the
center of mass. The center of bloodflow was located near (1 cm) the
center of mass. Thecoefficients (ag) and intercept in the linear
equation (Eq. 6)describe the mean blood flow at an arbitrary
position (x, y, z)within the lung. The coefficients a, b, and c
define the bloodflow gradients with respect to the x, y, and z
coordinate axes,respectively, at the center of mass. The
coefficients d, e, andf describe the variation of a gradient in one
coordinate axiswith respect to another axis, for example, the
partial deriv-ative of Q with respect to x results in the following
equationdescribing the blood flow gradient in the x direction
Q/x a dy fz gyz (6)
For y z 0 and at any x, the vertical gradient is equal tothe
coefficient a. At y 0, the vertical gradient is equal to
Q/x a fz (7)
That is, it varies linearly with z, and the coefficient f is
theslope of the vertical gradient in the z direction. Thus
bothblood flow and blood flow gradient in any coordinate axis canbe
calculated for any arbitrary position within the lung.Inclusion of
the xy, xz, and yz terms avoids analyzing sepa-rate lung regions to
obtain regional spatial gradients.
The regression analysis provides a P value, a measure ofthe
reliability, for each constant in best-fit linear equation.The
coefficient of determination (R2) represented the degreeof
variability due to spatial variation.
VA/Q heterogeneity. We evaluated the heterogeneity of VA,Q and
VA/Q distributions using the coefficient of variation(), the
standard deviation of regional VA and Q values
divided by mean values. Variance (2) of VA/Q was computedfrom
the variances of VA and Q with Pearsons correlationcoefficient (c)
between VA and Q (50)
2VA/Q 2VA 2Q 2VA Q (8)
Heterogeneity in VA/Q measured by the log-normal
standarddeviations (lnSDVA and lnSDQ) of VA- and Q-VA/Q
distribu-tion curves was obtained from MIGET and the
fluorescentmicrospheres (FMS) data.
To separate the heterogeneity in VA, Q, and VA/Q due tospatial
variations from that due to other factors (residualvariation), the
variance (mean summed squares) of the meansummed square of the
residuals, (measured predictedvalues)/mean value (50), was obtained
from the multiplelinear regression analysis. This analysis was
repeated usinga fourth-order regression equation (31 terms) with
terms upto third order in each coordinate and up to fourth order
ineach term (xpyqzr, p q r 4). Preliminary analysisindicated no
further decrease in the residual variance (orincrease in R2) with a
higher order regression equation. Theresidual variance/total
variance equals 1 R2, where R2 isthe adjusted coefficient of
determination from the regressionanalysis.
RESULTS
Physiological Data
Table 1 summarizes the physiological data. Bodyposition and PEEP
had no effect on QT, heart rate,temperature, respiration rate, pH,
mixed venous PO2,and hemoglobin. PEEP decreased Psa and
increasedPpa, Ppcw, and peak Paw in both LLD and RLD pos-tures.
Arterial PO2 (PaO2) was greater in the LLD thanRLD posture, whereas
A-aDO2 was less in the LLDthan RLD posture. The addition of PEEP
increasedPaCO2 by 2 Torr in both postures. PEEP increasedFRC by 65
and 76% in the LLD and RLD postures,respectively.
QS/QT and VD/VT showed no change between theLLD (0.15 0.3 and
43.5 4.8%) and RLD (0.18 0.24 and 43.6 4.6%) postures. PEEP
increased VD/VTin both the LLD (49.1 8.5%) and RLD (48.9
6.7%)postures and decreased QS/QT in the LLD (0.03 0.05%) but not
the RLD (0.15 0.24%) posture. QS/QTwas similar to that measured by
the FMS data. VD/VTwas greater than that measured by Fowlers
method(Table 1).
Microsphere data. In total, 1,3781,654 lung piecesper animal
were processed for Q and VA. We dis-carded lung pieces (135 49)
with 25% pulmonaryairways and with fluorescent intensity (11 10)
out-side the range of 4 SD of any of the mean values.Analysis of
blood flow and ventilation was carried outon 90.4 5% of the total
lung pieces. For the analysisof VA/Q and PrO2, we accepted data
with the range ofmean 3 SD of ln(VA/Q). This eliminated the
piecesassociated with dead space (very large VA/Q) and withshunt
(very low VA/Q). The number of pieces elimi-nated averaged 3 4% of
the total.
Spatial Gradients in Q, VA, VA/Q, and PrO2Multiple regression
analyses revealed systematic
variations of blood flow in the three coordinates. Be-
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cause the blood flow distribution described by the mul-tiple
linear regression equation (Eq. 5) for each animalshowed that most
(6 of 7) coefficients were significant,we used the equation to
describe Q, VA, VA/Q, and PrO2for all conditions. The use of the
equation was furtherjustified because R2 for the best-fit
regression waslower when only terms of one or two coordinates
wereincluded. The coefficients of the six animals werepooled for
each condition, and the significance wastested to determine its
validity in describing the bloodflow distribution. In many
instances, coefficients thatwere significant in a single animal
proved to be notsignificant among the six animals. Coefficients
were con-sidered meaningful only if the coefficients of the
sixanimals were significant. The present study showed val-ues of R2
of 0.40, indicating that 40% of the vari-ability in blood flow was
attributed to spatial variations.
Significant vertical, dorsal-ventral and caudal-cra-nial spatial
gradients of Q, VA, VA/Q, and PrO2 aresummarized in Table 2. The
complete set of pooledcoefficients are given in Tables A2 and A3
(APPENDIX).Figure 1 shows Q plotted vs. vertical height (x
coordi-nate) up the lung in the LLD and RLD postures withand
without PEEP for a representative animal. Thelines represent Q vs.
height (x) at the center of mass (yz 0), determined from the
regression analysis. Figures2, 3, and 4 are equivalent data for VA,
VA/Q, and PrO2.
Effect of Posture Without PEEP
Regional distribution of Q. As indicated by the xcoefficient (a)
for the whole lung, there was a signifi-cant negative
(gravity-dependent) vertical gradient(Table 2, 0.27 and 0.42 ml
min1 ml1 cm1) in Qthat was greater in the RLD posture (0.42) than
in
the LLD posture (0.27), implying that blood flow inthe dependent
lung was less in the LLD than in theRLD posture.
A smaller blood flow in the dependent lung in theLLD than RLD
posture was verified by the fact thattotal blood flow (% total) was
less in the dependentleft lung (37%) than in the nondependent lung
(63%)in the LLD posture but was greater in the dependentright lung
(64%) than in the nondependent lung(36%) in the RLD posture (Table
3). Given the sameQT in both postures (Table 1), the fraction of
the QTadjusted for tissue mass to either lung did not change
withbody position.
In both left and right lung, the vertical gradients(0.60 and
0.37) observed in the LLD posture wereeliminated with body
inversion to the RLD posture.These gradients represented a 70150%
change in themean blood flow over the height of the lung (15 cm)
or510% cm1.
In the left lung, there was a positive dorsal-ventralgradient
(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 accom-panied with a negative caudal-cranial gradient
in theLLD posture (0.18), with blood flow greatest in thecaudal
regions.
Regional distribution of VA. For the whole lung, thelargest
vertical gradient in VA was observed in theRLD posture (Table 2,
0.58) and occurred in conjunc-tion with a positive dorsal-ventral
gradient (0.31) thatwas eliminated with inversion to the LLD
posture. Inthe LLD posture, the only substantial gradient oc-curred
in the dorsal-ventral direction (0.27).
Table 2. Significant* spatial gradients and intercepts of
regression equation
Lung Position Intercept Vertical (a) Dorsal-Ventral (b)
Caudal-Cranial (c)
Q Whole LLD 5.02.1 0.270.11 0.0790.032RLD 5.21.5 0.420.39
0.0740.049
Q Left LLD 5.82.2 0.600.40 0.260.24 0.180.11RLD 3.91.4
0.180.15
Q Right LLD 4.62.2 0.370.22RLD 5.83.8
VA Whole LLD 5.11.4 0.270.25RLD 5.51.4 0.580.34 0.310.25
VA Left LLD 4.61.8 0.410.22RLD 3.20.9 0.200.16 0.270.20
VA Right LLD 5.51.7 0.500.21RLD 6.92.3 0.640.58
VA/Q Whole LLD 1.210.50RLD 1.080.43 0.0350.02
VA/Q Left LLD 0.920.38 0.0530.03RLD 1.020.53
VA/Q Right LLD 1.400.6RLD 1.090.39 0.0350.022
PrO2 Whole LLD 113.46.7 1.301.2 1.150.89 0.500.26RLD 111.38.7
1.430.73
PrO2 Left LLD 104.912 2.802.60 0.850.67RLD 109.212 1.981.70
PrO2 Right LLD 118.64.3RLD 112.67.3
Values are means SD (n 6). Q, perfusion; VA, ventilation; PrO2,
regional PO2. *P 0.05, compared with zero by 1-tailed
t-test.Equation: Variable I ax by cz dxy eyz fzx gxyz. All
intercepts are significant.
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Similar to the behavior in QT, total ventilation wassmaller in
the dependent lung than in the nondepen-dent lung in the LLD
posture but larger in the depen-dent lung in the RLD posture (Table
3). For constantventilation in both postures, body position had no
effecton ventilation in either lung. In the left lung in theRLD
posture, significant vertical (0.20) and dorsal-ventral (0.27)
gradients were observed.
Relationship between regional and total blood flowand
ventilation for each lung. The vertical gradients inQ and VA (Table
2) measured in this study mightappear at first sight to be at odds
with the total bloodflow and ventilation values measured for each
lung(Table 3). For the whole lung, the vertical gradient in Qin the
LLD posture would suggest a greater blood flowin the dependent lung
than in the nondependent lung(Table 2). On the other hand, the
total blood flow to thedependent left lung in the LLD posture was
clearlylower than that to the nondependent lung. This appar-ent
discrepancy is due to the fact that the total bloodflow to the lung
is the product of the mean regional Qand the total lung volume.
This relationship allowed theestimate of FRC to each lung. The
smallest FRC waspredicted to occur in the left lung in the LLD
posture.
In the LLD posture, mean Q (Table A2) averaged 5.8and 4.6 ml
min1 ml1 in the left and right lungpieces, respectively. QT (3.6
l/min) was distributed 1.3
l/min (37%) to the left lung and 2.3 l/min (67%) to theright
lung (Table 3). Thus the estimated FRC was 220ml in the left lung
and 500 ml in the right lung,resulting in a total FRC of 720 ml.
This value was closeto the measured value (758 ml) equal to the air
volume(645 ml, Table 1) and wet tissue volume (113 ml) basedon lung
wet weight (4.7 24 g dry weight). Thepredicted left lung FRC was
31% total FRC. The ex-pected FRC of a uniformly inflated left lung
based ontissue mass was 43% total FRC. This value was re-duced by
25% via the vertical Ptp gradient, resultingin a left lung FRC of
32%, near the predicted value of31%. Accordingly, the reduced blood
flow to the depen-dent left lung in the LLD posture was consistent
witha reduced FRC caused by the vertical Ptp gradient.Evidently
vertical gradients in Q require knowing re-gional lung volume to
accurately predict relative bloodflow to each lung. A similar
argument applies to VAmeasurements.
Regional distribution of PrO2 and VA/Q. The largestgradient in
PrO2 (1.3, Table 2) was observed in thevertical direction for the
whole lung in the LLD postureand was positive, indicating that PrO2
was smaller inthe dependent (left) lung than in the
nondependent(right) lung (intercepts, Table A3). This vertical
gradi-ent was abolished with inversion to the RLD posture
Fig. 1. Blood flow (Q) per unit regionallung volume (ml min1
ml1) vs. lungheight for a representative dog in theleft lateral
decubitus (LLD) posturewithout positive end-expiratory pres-sure
(PEEP; A), LLD with 10 cmH2OPEEP (B), right lateral decubitus(RLD)
posture without PEEP (C), andRLD with 10 cmH2O PEEP (D). R,right
lung (E); L, left lung ({). Linesrepresent best-fit values from
multiplelinear regression analysis. R2 indi-cated that 40% of the
variability inblood flow was spatially determined.WL, whole lung;
RL, right lung; LL,left lung. Independent and dependentaxes have
been interchanged for pre-sentation.
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and was accompanied with positive dorsal-ventral
andcaudal-cranial gradients.
To determine whether PrO2 observed in the depen-dent lung in the
LLD posture was low enough to triggera hypoxic vasoconstriction
response, the minimum PrO2value was obtained from regression
analysis for the sixanimals studied. Substituting into Eq. 5, the
linearequation with mean intercept and coefficients for thewhole
lung was as follows (Table A3)
PrO2 113 1.3x 1.15y 0.5z 0.14xy 0.16yz
0.06zx 0.03xyz
The minimum value of PrO2 (81 21 Torr) occurred inthe dependent
(x 4 cm), dorsal (y 5 cm), andcaudal (z 8 cm) regions of the lung
(Fig. 6). Themaximum value of PrO2 (124 5 Torr) was located inthe
nondependent (x 4 cm), ventral (y 5 cm),and cranial (z 8 cm) region
of the lung. In the RLDposture, minimum and maximum PrO2 values
evalu-ated at similar (x, y, z) values used for the LLD posturewere
96 10 and 117 8 Torr, respectively (Fig. 6).Note that PrO2 was
reduced below 100 Torr only in thedependent lung in the LLD
posture.
The low PrO2 originating from the dependent caudal-dorsal
regions of the dependent left lung in the LLDposture without PEEP
was increased by inversion tothe RLD posture (Fig. 4). That body
inversion from theLLD to the RLD posture increased PrO2 in the
caudal
regions was consistent with the reduction or eliminationof
significant positive vertical, dorsal-ventral, and cau-dal-cranial
PrO2 gradients for the whole lung (Table 2).
In the left and right lung, small but significant gra-dients in
PrO2 and VA/Q were observed in all threecoordinates (Table 2).
However, the detection of a sig-nificant VA/Q (PrO2) gradient was
associated with asignificant PrO2 (VA/Q) gradient only in the left
depen-dent lung in the LLD posture. In the left (dependent)lung in
the LLD posture, a dorsal-ventral VA/Q gradi-ent (0.053) was
associated with significant PrO2 gradi-ents (2.8).
Comparison Between Predicted and MeasuredGas Exchange
Predicted PaO2 and PaCO2 calculated from regionalVA/Q data did
not differ from measured PaO2 and PaCO2in both the LLD and RLD
posture (Table 1), and themeasured A-aDO2 was well predicted from
the micro-sphere data in the LLD posture. However, the pre-dicted
values of A-aDO2 were significantly (P 0.05)less in the LLD than in
the RLD posture (Table 1).
Mean VA/Q and PrO2 Changes of Nondependentand Dependent Lung
In the LLD posture (intercepts, Table 2), VA/Q wasgreater in the
nondependent right lung (1.42 0.45)
Fig. 2. Ventilation (VA) per unit regionallung volume (ml min1
ml1) vs. lungheight for representative animal in LLDwithout PEEP
(A), LLD with 10 cmH2OPEEP (B), RLD without PEEP (C), andRLD with
10 cmH2O PEEP (D). Lines rep-resent best-fit values from multiple
linearregression analysis.
751LATERAL POSTURE AND PEEP ON VA AND Q
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than in the dependent lung (0.93 0.37). In the rightlung, PrO2
increased with body inversion from the RLD(113 7 Torr) to the LLD
(119 4 Torr) posture. Thiswas associated with an increase in VA/Q
from 1.09
0.39 in the RLD posture to 1.40 0.60 in the LLDposture. This
behavior was accompanied with a dorsal-ventral VA/Q gradient that
was significant (0.035) onlyin the RLD posture.
Fig. 3. VA-to-Q ratio vs. lung height forrepresentative animal
in LLD withoutPEEP (A), LLD with 10 cmH2O cmPEEP (B), RLD without
PEEP (C), andRLD with 10 cmH2O PEEP (D). Linesrepresent best-fit
values from multiplelinear regression analysis.
Fig. 4. Regional PO2 (PrO2) vs. lung height forrepresentative
animal in LLD without PEEP(A), LLD with 10 cmH2O cm PEEP (B),
RLDwithout PEEP (C), and RLD with 10 cmH2OPEEP (D). Lines represent
best-fit valuesfrom multiple linear regression analysis.Note that
the low PCO2 values in the depen-dent lung in the LLD posture (A)
was elimi-nated with the addition of PEEP (B).
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Regional Variations in the Spatial Gradients
The significant coefficients d, e, and f, shown inTables A2 and
A3 indicated that the spatial gradientsvaried along an orthogonal
axis. These are discussed inthe APPENDIX.
Effect of PEEP
Regional distribution of Q. In general, PEEP eitherreduced or
eliminated the spatial gradients in Q and VAthat occurred without
PEEP (Table A2). The decrease inthe vertical gradient with PEEP was
associated with adecrease (3050%) in the mean blood flow
(intercepts,Table A2). With PEEP, the dependent right lung in
theRLD posture had the greater blood flow, similar to thebehavior
without PEEP (Table 3). By contrast, in theLLD posture PEEP
eliminated the left-right lung differ-ence in blood flow measured
without PEEP.
PEEP increased the low PrO2 originating from thedependent
caudal-dorsal regions of the dependent leftlung in the LLD posture
(intercepts, Table A3). The lattereffect of PEEP was consistent
with the PEEP-inducedreduction of the caudal-cranial VA/Q gradient
(from 0.053to 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 PaO2and PaCO2
calculated from VA/Q data did not differ frommeasured PaO2 and
PaCO2 in both the LLD and RLD
posture, and the measured A-aDO2 was well predictedfrom the
microsphere data (Table 1).
PEEP reduced the relatively high VA/Q of the non-dependent right
lung to a value closer to 1 (Table A3,1.22 0.24). In the right lung
with PEEP, VA/Q in-creased 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 increasedPrO2 from 105
12 to 112 7 Torr (Table A3). Thisbehavior was associated with a
PEEP-induced verticalPrO2 gradient (0.83) in conjunction with
reduced dor-sal-ventral and caudal-cranial PrO2 gradients.
Regional Perfusion Correlation Between PosturesWith and Without
PEEP
Figure 5 shows Q to each lung piece in the LLD postureplotted
against blood flow of the same piece in the RLDposture of one
representative animal without PEEP (Fig.5A) and with PEEP (Fig.
5B). Except for the left lungwithout PEEP (R 0.66), blood flow to
each piece waspoorly correlated (R 0.0440.22) between LLD andRLD
posture. In other words, lung pieces with high (orlow) blood flow
in the LLD posture received low (or high)blood flow in the RLD
posture. This behavior was consis-tent with the gravity-dependent
vertical gradients ob-served for both right and left lungs and for
the whole lungin both postures, opposite to that found between
thesupine and prone position (19).
Q and VA heterogeneity. The mean coefficients ofvariation of Q
and VA (3060%) were similar to re-ported values (19, 21, 29, 33,
40). Table 4 summarizesthe heterogeneity in VA and Q evaluated by
threemethods: total and residual variances of VA, Q, andVA/Q;
widths (lnSDVA and lnSDQ) of the VA-VA/Qand Q-VA/Q distribution
curves measured by FMS andMIGET. The variance of the data based on
regionalvalues was similar to that based on uncorrected data.The
coefficients of correlation (c) between VA and Q(Pearsons method)
were similar to those computed byuse of VA, Q, and 2VA/Q in Eq. 8
(33). The totalvariance data showed that in the LLD posture
PEEPreduced the variance in VA and VA/Q but not in Q,
Table 3. Percent cardiac output and ventilation toleft and right
lung from microsphere data
PEEP, cmH2O
LLD RLD
0 10 0 10
Q, % Left lung 376 498* 364 325Q, % Right lung 636 518* 644
685VA, % Left lung 286 436* 349 377VA, % Right lung 726 576* 669
637
Values are means SD (n 6). *P 0.05, significant changewith PEEP;
P 0.05, significant difference with change in pos-ture; P 0.05,
significant difference between left lung and rightlung.
Fig. 5. Correlation between pulmonaryblood flow in the LLD and
RLD measuredin 1 representative animal without PEEP(A) and with
PEEP (B). Dotted line is lineof identity. Note that lung pieces
with high(low) blood flow in the LLD posture re-ceived low (high)
blood flow in the RLDposture, consistent with a gravity-depen-dent
vertical gradient measured by multi-ple linear regression analysis
(Fig. 1B).
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consistent with a more uniformly inflated lung at thehigher lung
volume. This PEEP-induced change invariance was undetected by the
other two methods.Neither body position nor PEEP affected the
totalvariance in Q. Neither PEEP nor body positionchanged the
correlation between VA and Q. There wasa tendency for heterogeneity
measured by lnSDVA andlnSDQ to be greater with MIGET than with FMS,
butthe difference was only significant for Q in the LLDposture
without PEEP. The broader distribution mea-sured with MIGET than
with topographical data hasbeen noted in previous studies (15, 45).
The differencehas been attributed to the coarse scale of the
VA/Qdistribution inherent in MIGET (4, 5).
Heterogeneity in VA, Q, and VA/Q that was attrib-uted to
residual variation as measured by the residualsof the regression
analysis was reduced from 65 16%of the total variance in the linear
regression analysis to41 6% of the total variance in the
fourth-orderregression analysis (Table 4). These values are in
linewith the coefficients of determination (R2) of 40 and60% that
implicated 60 and 40% of the variability toresidual variation.
Similar to the total variance, PEEPreduced the residual variance of
VA in the RLD posture.Neither body position nor PEEP affected the
residualvariance in Q. There was a tendency for PEEP to in-crease
the residual-to-total variance fraction in VA andVA/Q, but this was
only significant in the LLD posture.
The coefficient of correlation (c) between VA and Qcalculated by
using the residual variances (0.590.75,Table 4) in Eq. 8 was
similar to the correlation coeffi-cient between VA and Q
(0.570.71).
DISCUSSION
In this study we used a high-resolution technique todescribe the
distribution of Q, VA, VA/Q, and PrO2 in thelateral decubitus
posture. The high resolution in con-junction with multiple linear
regression analysis al-lowed the spatial description of these
variables at anyarbitrary position relative to the three
rectangularcoordinate axes.
The major findings of this study are as follows. First,the
gravity-dependent vertical gradient in Q wasgreater in the RLD than
LLD posture (Fig. 1, A and B;Table 2). This was attributed to a
reduced blood flow inthe dependent left lung in the LLD posture
(Table 3).Second, PEEP reduced the vertical gradient in
bothpostures and eliminated the difference between pos-tures (Fig.
1). PEEP or body inversion from the LLD tothe RLD posture abolished
the positive vertical, dorsal-ventral, and caudal-cranial gradients
in PrO2 observedin the LLD posture (Table A3). Third, a positive
verti-cal gradient in PrO2 was observed in the LLD posturewith the
dependent dorsal-caudal regions of the depen-dent lung having
values below that (100 Torr) needed
Table 4. Effect of position and PEEP on heterogeneity of VA and
Q distribution: FMS and MIGET
Method 2, lnSD or c
ZEEP PEEP
LLD RLD LLD RLD
FMS (total)2VA 0.220.05 0.390.22 0.160.01* 0.140.022Q 0.150.07
0.230.12 0.130.05 0.160.052VA/Q 0.310.16 0.260.12 0.110.04*
0.130.03c(VA:Q) 0.570.16 0.710.17 0.660.14 0.650.14
Residual (linear)2VA 0.140.04 0.210.07 0.140.04 0.120.052Q
0.090.02 0.120.04 0.090.04 0.100.062VA/Q 0.080.04 0.090.06 0.070.02
0.080.03c(VA:Q) 0.650.12 0.750.12 0.710.10 0.610.12
Residual/total (%), linear2VA 6616 6626 8922 90442Q 6517 7145
6921 64352VA/Q 3217 4226 6316* 6515
Residual (4th order)2VA 0.080.03 0.090.06 0.070.04 0.080.052Q
0.140.04 0.180.12 0.110.04 0.100.042VA/Q 0.090.04 0.090.05 0.070.02
0.090.05c(VA:Q) 0.590.16 0.710.06 0.640.12 0.500.18
Residual/total (%), 4th order2VA 3413 3718 4816 47352Q 3513 328
4717 45312VA/Q 3613 3715 4813 4531
FMSlnSDVA 0.400.07 0.360.07 0.300.04 0.360.07lnSDQ 0.450.16
0.480.18 0.350.07 0.360.08
MIGETlnSDVA 1.070.60 1.040.59 1.000.57 1.240.54lnSDQ 0.710.24
0.600.14 0.680.40 0.520.17
Data are means SD (n 6), except for multiple inert gas
elimination technique (MIGET, n 5). 2, variance; c, correlation
coefficientbetween VA and Q; lnSDVA and lnSDQ, log-normal standard
deviation of VA- and Q-VA/Q distributions. *P 0.05 compared with
ZEEP inLLD; P 0.05 compared with ZEEP in RLD; P 0.02 compared with
MIGET.
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to invoke a hypoxic vasoconstriction response (31). Thisbehavior
was consistent with the reduced blood flow tothe dependent lung in
the LLD posture.
Methodological Issues
Fluorescent microsphere technique. The microspheretechnique as
implemented in this study has been val-idated in previous studies
(17, 40). Regional depositionof aerosolized and injected
microspheres allowed si-multaneous measurements of ventilation and
perfu-sion distribution that predicted regional gas exchangewith
high spatial resolution.
Volume adjustment to FRC and vertical Ptp gradi-ent. Injected
and aerosolized fluorescent microsphereswere delivered in vivo near
FRC, whereas the fluores-cent signals were measured in vitro in the
dried lunginflated to TLC. Accordingly, we made several
adjust-ments to the weight of each piece to extrapolate topiece
volume in vivo and to determine Q and VA perunit regional lung
volume at FRC.
First, the lung volume of each piece was adjustedfrom TLC to FRC
by reducing the cube lengths in thethree dimensions. This
adjustment resulted in ananisotropically inflated lung (20) and a
homogeneous(constant) deformation along each axis. Second,
weimposed a distortion to the vertical dimension (x) ofeach lung
piece to produce a vertical Ptp gradient aspreviously measured (1).
This distortion in the x di-mension at each height was based on the
PV curve ofan isolated lung (27) and was applied to all y and
zdimensions at the same height. This preserved thehomogeneous
deformation in the y and z coordinatesand the anisotropy in
regional volume at FRC, in effectproducing changes in regional
volume identical tothose given by the PV curve (Eq. 2). These
adjustmentsfor the vertical Ptp gradient increased the
(maximum)dependent (D)-to-nondependent (N) ratio (D/N) for Qby a
factor of 3, N/D in regional lung volume, andD/N in regional lung
density (16). Implicit in thisadjustment for lung density is the
scaling of tissuemass to capillary density. Accordingly, regional
lungdensity changes caused by the vertical Ptp gradientwere the
dominant contributor to the vertical gradientin Q and VA.
Prior studies have reported the vertical gradients ofperfusion
relative to the number of alveoli or pieceweight at TLC. This paper
presents perfusion gradi-ents relative to the regional lung volume
at the time ofmicrosphere injections. The adjustment for the
verticalchanges in regional lung density produced verticalgradients
in regional Q that were greater than thoseestimated in previous
studies using TLC-measuredregional volume (18, 19, 21, 22, 33, 34).
These normal-ization issues need further evaluation, particularly
inthe supine and upright body positions under both nor-mal and
increased acceleration loads with relativelylarge Ptp gradients (1,
2).
We made no adjustment for Ptp gradients in theother two axes (y
and z), in the absence of reporteddata. Blood volume was ignored in
the calculation of
lung density and regional lung volume because the dryweight used
in the calculation of mean lung densitywas blood free.
Distribution of Regional Perfusion
Effect of gravity. The effects of gravity on the
verticalgradient in blood flow in the lung have been describedin
terms of the relation among the Ppa and pulmonaryvenous (Ppv) and
alveolar (Palv) pressures (48, 49).This theory predicts a
decreasing blood flow up theheight of the lung (in our
nomenclature, a negativevertical gradient). Most of the vertical
gradients mea-sured in the present study are explainable, at
leastqualitatively, with the gravitational model. The verti-cal
gradients in blood flow measured in the LLD andRLD posture with and
without PEEP were expectedand confirmed previous findings (6, 20,
25, 28, 37).
Effect of lung volume and vascular resistance. Thefact that the
gravity-dependent vertical gradients in Qdecreased with a change
from RLD to LLD posture andwith PEEP indicates that factors other
than gravitycontributed to the blood flow distribution. A
majorfactor was the lung volume-induced vascular resis-tance that
changed with body position and PEEP. Pul-monary vascular resistance
depends on lung volume(24); its changes with lung volume are
different forzone 2 (Ppa Palv Ppv) and zone 3 (Ppa Ppv Palv)
conditions (9). By this theory (24), Q is propor-tional to Ppa Palv
in zone 2 and Ppa Ppv in zone3. The increased flow down the lung is
due to Ppaincreasing down the lung in zone 2 and to
Ppv-inducedcapillary recruitment or vascular distention in zone
3.
In the latter study (9), pulmonary blood flow andvascular
resistance were measured vs. lung volume(%TLC) at constant values
of Ppa Palv and Ppv Palv under both zone 2 and zone 3 conditions in
iso-lated rabbit lungs. In zone 3, for Ppa-Palv of 18 mmHg,blood
flow increased linearly with a decrease in lungvolume from TLC to
residual volume. In zone 2, bloodflow increased as lung volume
decreased from TLC to50% TLC but decreased from 60% TLC to
residualvolume, a behavior consistent with the U-shape
curvedescribing the relationship between vascular resis-tance and
lung volume (44). Whatever the lung vol-ume-induced differences in
blood flow, blood flow wasgreater in zone 3 than in zone 2.
In the present study, without PEEP, Ppv averaged8.4 cmH2O in the
LLD posture and 6.1 cmH2O in theRLD posture (Table 1, Ppcw)
relative to mid-heartlevel. With a mean Paw of 5 cmH2O (Table 1),
thedependent lung was in zone 3 in both postures whereasthe
nondependent lung was predominantly in zone 2,more so in the RLD
than in the LLD posture. PEEPincreased Ppv to 10 cmH2O and mean Paw
to 15cmH2O in both postures, placing the nondependentlung and half
of the dependent lung in zone 2. Pulmo-nary vascular resistance,
(Ppa Ppcw)/blood flow, wasgreater in the dependent than
nondependent lung inboth postures and increased with PEEP (Table
1).
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The gravity-dependent vertical gradients in bloodflow measured
in both postures for the whole lungwithout PEEP (Table 2, Fig. 1, A
and C) were consis-tent with the shift from zone 2 to zone 3
conditionsdown the lung, but these gradients were accentuatedby the
threefold increase in lung density down thelung. The removal of the
density gradient with PEEPreduced the gradients to 44 and 33% in
the LLD andRLD posture, respectively (Table 2, Fig. 1, B and
D).Thus the two- to threefold increase in the gradient withthe
removal of PEEP was attributed almost entirely tothe lung density
gradient. A similar behavior was ob-served for both left and right
lungs in the LLD posture(Fig. 1, A and B).
Blood flow was lower in the dependent left lung thanin the
nondependent lung (Table 3), consistent with theresults of a
previous study (28). This behavior wasopposite to that predicted by
gravity, indicating thatfactors other than gravity contributed to
blood flowdistribution in the LLD posture. One factor has
beenassociated with the vascular structure (17, 28). Thereduced
blood flow to the dependent left lung was notcaused by a heart
weight induced lower lung volumeper se because a reduced lung
volume is associatedwith a lower vascular resistance in zone 3 (9).
It ispossible that a nonuniform lung distortion due to heartand
abdominal weight might conceivably cause an in-creased vascular
resistance. Another mechanism suchas hypoxic vasoconstriction
remains an alternative ex-planation in vivo, particularly in view
of the positivegradient in PrO2 measured (see below).
Nongravitational gradients in Q. An important find-ing of this
study relates to other nongravitational gra-dients in Q.
Specifically, in the isogravitational ( y-z)plane (x 0), a positive
dorsal-ventral gradient in Qoccurred in the left dependent lung in
the LLD posture,with blood flow maximal in the ventral regions
(Table2, 0.26). The smaller blood flow in the dorsal regionswas
opposite to that observed in the supine dog (10) inwhich the dorsal
lung regions had the larger blood flow.Thus the present
measurements would not support anintrinsic greater vascular
conductance postulated forthe dorsal lung regions (10). Thus
extrinsic factorssuch as hypoxic vasoconstriction and lung
distortioncaused by the weight of the heart and abdomen mightbe
crucial.
The positive dorsal-ventral gradient in Q observed inthe left
lung in the LLD posture occurred in conjunc-tion with a negative
caudal-cranial gradient in Q withQ increasing in the caudal region,
in the absence of anygradient in the right lung. Both these
gradients wereabolished with PEEP, indicating a lung
volume-in-duced relative shift of blood flow from the
ventral-caudal to the dorsal-cranial regions.
The decrease in blood flow in the caudal-cranialdirection for
the whole lung in the LLD posture isconsistent with the results of
Greenleaf et al. (20) inthe mechanically ventilated anesthetized
dog. Thiscontrasts to the absence of a caudal-cranial gradient
inspontaneously breathing humans in the lateral decub-itus posture
(6).
Distribution of Ventilation
Effect of posture without PEEP. In contrast to theabsence of a
vertical VA gradient in the LLD posture(Table 2), total ventilation
was greater in the nonde-pendent than dependent lung in the LLD
posture (Ta-ble 3). This difference was similar to the behavior
inblood flow and was most likely due to a smaller FRC inthe
dependent left lung. Body inversion from LLD toRLD posture produced
a substantial negative gradientin VA (0.58) that was consistent
with the greater totalventilation measured in the right dependent
lung thanin the nondependent lung. This behavior in the
anes-thetized dog is consistent with results from the anes-thetized
human in the lateral decubitus posture (38,39). These results with
anesthesia differed substan-tially from those in awake humans,
showing greaterventilation in the dependent than nondependent
lungin both the LLD and RLD posture (7, 25, 32). The latterbehavior
was explained by the vertical Ptp gradientcausing a lower lung
volume and greater lung compli-ance in the dependent lung regions.
The absence of acaudal-cranial gradient in VA in the lateral
decubitusposture in the anesthetized dog was consistent withthe
results in awake humans measured by using radio-active gas
inhalation and external scintillationcounters (7, 25). This
behavior was attributed to auniform Ptp in the horizontal
direction.
The differences in ventilation measured between theanesthetized
and awake state might be related to theanesthesia-induced reduction
in FRC observed in bothlungs (38, 39). The following factors might
be involved.First, the nondependent lung would move from theupper
low-compliant part of its PV curve during awakebreathing to the
lower high-compliant part after anes-thesia, resulting in better
ventilation. Second, the clos-ing volume of the dependent lung
might be greaterthan its FRC (36), consistent with the absence of
ven-tilation to part of the dependent lung and with
reducedventilation. Third, atelectasis and small airway closurein
the dependent lung with its lower Ptp and greaterclosing volume
would serve to shunt ventilation to thenondependent lung. Fourth,
in addition to the anesthe-sia-induced reduction in FRC, the weight
of the heartand abdomen would compress the dependent lung andexpand
the nondependent lung. This effect of gravitywould be greater in
the smaller dependent left lung inthe LLD posture than the
relatively larger dependentright lung in the RLD posture,
accounting for thedifference between the two postures.
Except for the left lung in the LLD posture, signifi-cant
negative vertical VA gradients were observed inthe left lung in the
RLD posture and in the right lungin both postures. These gradients
were accentuated bythe imposed vertical gradient in regional
volume. Inaddition, a positive dorsal-ventral gradient in VA
wasobserved in the left lung in both postures. The reasonfor this
gradient was not apparent.
Effects of PEEP. Like the blood flow distribution,PEEP reduced
the difference in Q between the depen-dent and nondependent lung in
the LLD posture (Fig.
756 LATERAL POSTURE AND PEEP ON VA AND Q
J Appl Physiol VOL 92 FEBRUARY 2002 www.jap.org
-
2, A and B, Table 3), similar to the behavior found inthe
anesthetized human (39) and dog (36). The PEEP-induced change in
the vertical gradient in VA in theLLD posture occurred in
conjunction with the elimina-tion of the positive dorsal-ventral
gradient in VA (TableA2). PEEP eliminated or reduced the negative
gradientin VA observed for the whole lung and left lung in theRLD
posture and in the right lung in both postures. Asimilar effect was
observed for dorsal-ventral gradientsfor the whole lung and for the
left lung in both pos-tures. Accordingly, in general the effect of
PEEP was toreduce the spatial variations in ventilation by
increas-ing regional lung volume to a less compliant part of thePV
curve where tidal-volume induced changes in air-way resistance are
minimal.
Distribution of Regional VA/Q
The VA/Q ratio was greater in the nondependentlung than in the
dependent lung in the LLD posture(Table A3). There was a tendency
(not significant) forthis behavior to be reversed in the RLD
posture withthe dependent lung having the greater VA/Q, consis-tent
with the results in the anesthetized human sub-jected to positive
airway pressure (28). The latter re-sult is supported by the
PEEP-induced increase in thevertical VA/Q gradient in the RLD
posture (Table A3).Furthermore, PEEP produced a positive vertical
gra-dient in VA/Q in the dependent lung in both postures.By
contrast, in keeping with the PEEP-induced reduc-tion in the
spatial variation in VA, PEEP eliminated orreduced the
dorsal-ventral gradient in VA/Q observedfor the whole lung in the
RLD posture and in thedependent lung in both postures. These
nongravita-tional gradients measured in the anesthetized dog
withPEEP were not observed in the awake human (6).
Distribution of PrO2A major advantage of the fluorescent
microsphere
technique over other techniques is the ability to mea-sure
regional values and spatial gradients in PrO2.Estimated PaO2
values, determined from a perfusion-weighted sum of PrO2,
calculated by using microspheremeasures of Q and VA, were
consistent with measuredPaO2 values in the anesthetized dog in the
presentstudy, confirming similar results in the pig (4). How-ever,
in the present study, microsphere data underes-timated A-aDO2. This
might be attributed to moreheterogeneous perfusion and ventilation
with thegreater spatial resolution (4).
On the basis of multiple linear regression analysis ofthe PrO2
data and the calculated spatial gradients, PrO2in the LLD posture
was greater in the nondependentventral and cranial lung regions
than in the dependentdorsal and caudal lung regions, respectively.
Thesedifferences were either eliminated or reduced withPEEP.
In the left lung in the LLD posture, PEEP increasedPrO2 from a
mean value of 106 11 to 112 7 Torr(Table A3). This was accompanied
with a PEEP-in-duced reduction of significant dorsal-ventral and
cau-
dal-cranial PrO2 gradients (Table A3). Accordingly, thedependent
lung in the LLD posture without PEEP hadthe lowest VA/Q (Table A3)
and the lowest PrO2. Inver-sion of the dependent lung to the
nondependent posi-tion and PEEP both served to increase VA/Q and
PrO2.
In general, the PrO2 distribution was less uniform inthe left
lung than in the right lung, especially in thedependent LLD
posture, and PEEP produced a moreuniform PrO2 distribution in the
dependent left lung.Compared with the dependent right lung in RLD
posi-tion, the greater lung distortion caused by the weightof the
heart and abdomen acting on the smaller depen-dent left lung in the
LLD posture might contribute to aless uniform PrO2
distribution.
Hypoxic Pulmonary Vasoconstriction and Zone 4
Many studies (19, 20, 24, 26, 36) have demonstratedthat blood
flow decreased in the most dependent lungregions (zone 4), opposite
to the behavior predictedfrom the effects of gravity in zone 3
(49). This behaviorhas been attributed to increased vascular
resistancecaused by hypoxic pulmonary vasoconstriction (19, 20,26,
36) or reduced vascular diameter in the most de-pendent lung
regions (19, 20, 26, 36). The latter effectwas attributed either to
a low lung volume or perivas-cular cuff formation due to increased
transvascularfluid flux (24).
Hypoxic pulmonary vasoconstriction might regulateregional
perfusion to match VA to achieve efficient gasexchange (30). Our
estimates of VA/Q and PrO2 pro-vided evidence that this mechanism
might be at workin the left dependent lung in the LLD posture. In
thepresent study, some lung pieces of the dependent lungin the LLD
posture showed relatively low PrO2 values(Fig. 4, A and C) that
were consistent with values(PrO2 100 Torr) associated with hypoxic
pulmonaryvasoconstriction (8, 12, 30). Estimates of PrO2 from
thedata analysis (Fig. 6) provided evidence that in the
Fig. 6. Minimum and maximum PrO2 values from best-fit
multiplelinear regression equation in the LLD and RLD postures. *P
0.05,LLD vs. RLD posture. The minimum PrO2 values in the LLD
postureare consistent with a hypoxic vasoconstriction response that
wouldaccount for the reduced blood flow measured in the dependent
leftlung (Table 3). x, y, and z, Vertical, dorsal-ventral, and
caudal-cranial axes, respectively.
757LATERAL POSTURE AND PEEP ON VA AND Q
J Appl Physiol VOL 92 FEBRUARY 2002 www.jap.org
-
LLD posture hypoxic vasoconstriction occurred in thedependent
lung, where total blood flow was reducedrelative to the
nondependent lung (Table 3). PEEPincreased both VA/Q and PrO2 in
the dependent leftlung (Figs. 3 and 4) and eliminated the hypoxic
vaso-constriction, resulting in a gravity dependent greaterblood
flow in the dependent lung than in the nonde-pendent lung.
Effect of Heart and Abdominal Weight on BloodFlow
Distribution
Many studies (3, 23, 35, 38, 41) have suggested thatlung volume
and blood flow of the dependent lung arereduced in the lateral
decubitus posture because of amediastinal shift due to heart and
abdominal weight.In the dog, the weight of the heart compressed
thedependent lung regions to a greater extent in thesupine than in
the prone position (23). The heartweight-induced change in lung
volume was greaterwith body inversion from LLD to RLD posture
thanfrom the prone to supine posture (35).
Mean Q calculated by the regression analysis indicatedthat the
PEEP-induced reduction in regional perfusionat the center of mass
near the heart was greater in thenondependent than in the dependent
lung (Table 2,intercepts). This effect was greater in the left than
inthe right lung. Thus the effect of PEEP on the bloodflow
distribution was greater in the left lung in theLLD posture than in
the right lung in the RLD posture.The difference in the
preinspiratory lung volume be-tween the left and right lung may be
involved, in viewof studies in anesthetized humans (38) showing
thatFRC of the right lung in the RLD posture was largerthan FRC of
left lung in the LLD posture, whereas FRCof the nondependent right
lung was similar to thedependent right lung in the RLD posture.
Thus thePEEP-induced lung expansion might be greater in theright
dependent lung than in the left dependent lungthat was closer to
its closing volume. The reduced effectof PEEP in the left dependent
lung in the LLD posturemight be exacerbated during anesthesia,
which might
reduce diaphragmatic tone and reduce the diaphrag-matic support
of abdominal weight (14, 41). Thus thenonuniform ventilation
distribution observed in theLLD posture can be alleviated by
inversion to the RLDor with PEEP.
Q and VA Heterogeneity
The Q and VA heterogeneity in this study as mea-sured by the
coefficient of variation of Q and VA (3060%) is consistent with
previous studies using fluores-cent microspheres (18, 19, 21, 29,
33, 34, 40). However,on the basis of a one-dimensional linear
regressionanalysis, the latter studies concluded that 90% of
theheterogeneity in Q was due to factors other than spa-tial
variation. By contrast, the multiple regressionanalysis in the
present study indicated that 40% ofthe variability in Q, VA, and
VA/Q distributions wasattributed to spatial variation (Table 4).
The contribu-tion (60%) by the residual variance in the Q
distribu-tion is near to that measured in the supine dog (11).
The factors that contributed to the residual varianceinclude
heterogeneity on a scale that was smaller than1 cm, the dimension
of the lung cube in which Q andVA were measured (50). The variances
of VA, Q, andVA/Q attributed to residual variation produced a
corre-lation between VA and Q similar to that produced bythe total
variability (0.65). This behavior in conjunc-tion with the 40% of
the total variance in VA/Q attrib-uted to residual variability
suggests that matching ofVA and Q is not predominantly associated
with randomvariability. The relative contribution of residual
vari-ability using multiple regression analysis in previousstudies
(18, 19, 21, 22, 29, 33, 34, 40) needs furtherevaluation.
In conclusion, blood flow to the dependent left lung inthe LLD
posture was lower than that expected becauseof gravity. The reduced
blood flow resulted from hy-poxic vasoconstriction that occurred
because of a re-duced ventilation to the dependent lung compressed
bythe mediastinal contents. These effects were abolished
Table A1. x, y, z Coordinate distances between center of mass
and original coordinate system at caudal edge(z0 0), left edge (x0
0), dorsal edge (y0 0) of the lung
PEEP, cmH2O
LLD
L (%)
RLD
L (%)0 10 0 10
Whole lungx 6.10.7 9.60.9 50 7.90.2 9.50.5 20y 6.50.4 8.60.5 30
6.50.4 8.60.5 30z 11.50.9 13.61.0 20 11.50.8 13.61.0 20
Right lungx 8.30.9 12.71.3 50 5.10.3 6.30.5 20y 7.30.4 9.00.6 20
6.60.5 9.00.6 30z 12.20.9 13.71.0 12 10.90.8 13.71.0 20
Left lungx 3.20.4 5.30.6 65 11.60.6 13.70.9 20y 5.50.3 8.00.6 45
6.50.4 8.00.6 20z 10.50.9 13.51.0 30 12.20.9 13.51.0 10
Values are means SD; n 6. LPEEP0 x,y,z coordinate distances (cm)
between center of mass and original coordinate system at caudaledge
at PEEP 0 cmH2O in lung; LPEEP10 x,y,z coordinate distances (cm)
between center of mass and original coordinate system at caudaledge
at PEEP 10 cmH2O in lung. L (LPEEP10LPEEP0)/LPEEP0 for x, y, z
respectively.
758 LATERAL POSTURE AND PEEP ON VA AND Q
J Appl Physiol VOL 92 FEBRUARY 2002 www.jap.org
-
Tab
leA
2.C
oeffi
cien
tsan
dR
2of
mu
ltip
leli
nea
rre
gres
sion
equ
atio
n
fit
toQ
and
VA
dat
afo
rw
hol
e,le
ft,
and
righ
tlu
ng,
resp
ecti
vely
Lu
ng
Pos
itio
nP
EE
PIn
terc
ept
ab
cd
ef
gR
2
QW
hol
eL
LD
05.
0
2.1
0.
27
0.11
*0.
078
0.09
0
0.07
9
0.03
2*
0.03
7
0.03
8
0.02
4
0.00
4*0.
046
0.02
4*0.
006
0.00
5*0.
44
0.12
LL
D10
2.8
0.7
0.
12
0.08
*
0.02
4
0.01
7*
0.02
1
0.01
6*
0.00
7
0.00
9
0.00
6
0.00
5*0.
005
0.00
5*0.
002
0.00
1*0.
42
0.13
RL
D0
5.2
1.5
0.
42
0.39
*0.
010
0.01
5
0.07
4
0.04
9*0.
035
0.02
8*
0.03
5
0.02
2*0.
011
0.01
40.
001
0.00
50.
23
0.13
RL
D10
2.5
0.8
0.
14
0.07
*
0.00
01
0.04
0.
021
0.02
70.
0001
0.00
2
0.00
4
0.00
6
0.00
1
0.00
6
0.00
02
0.00
10.
56
0.15
QL
eft
LL
D0
5.8
2.2
0.
60
0.40
*0.
26
0.24
*
0.18
0.11
*0.
11
0.14
0.
074
0.03
*0.
041
0.04
60.
020
0.01
6*0.
52
0.14
LL
D10
4.0
1.1
0.
15
0.12
*0.
09
0.05
0.
012
0.02
0.02
0.01
5*
0.01
9
0.00
8*
0.00
3
0.00
60.
003
0.00
2*0.
37
0.09
RL
D0
3.9
1.4
0.
04
0.19
0.18
0.15
*
0.04
0.06
0.
037
0.02
*
0.03
3
0.02
1*0.
007
0.00
8
0.00
02
0.00
30.
39
0.11
RL
D10
1.9
0.8
0.
06
0.04
*0.
006
0.04
5
0.02
4
0.01
9*
0.02
4
0.01
9
0.00
7
0.00
5*0.
004
0.05
0.
0000
7
0.00
20.
27
0.11
QR
igh
tL
LD
04.
6
2.2
0.
37
0.22
*
0.06
0.09
0.00
6
0.03
0.
001
0.02
0.
014
0.01
40.
015
0.01
2*0.
005
0.00
4*0.
39
0.06
LL
D10
2.4
0.7
0.
12
0.05
*
0.07
0.04
3*
0.00
8
0.02
0.
005
0.00
2*
0.00
2
0.00
40.
007
0.00
5*0.
001
0.00
10.
37
0.1
RL
D0
5.8
3.8
0.
56
0.68
0.
006
0.2
0.
065
0.11
0.03
0.05
3
0.04
6
0.05
70.
064
0.06
10.
1
0.24
0.47
0.17
RL
D10
3.4
1.2
0.
14
0.11
*
0.01
5
0.04
2
0.01
6
0.04
60.
001
0.07
0.
006
0.00
90.
004
0.01
50.
001
0.00
20.
37
0.18
VA
Wh
ole
LL
D0
5.1
1.4
0.
068
0.27
0.27
0.25
*
0.03
0.10
0.
053
0.04
*
0.04
3
0.02
6*0.
04
0.02
*0.
009
0.00
9*0.
39
0.11
LL
D10
2.9
0.7
0.
072
0.06
*
0.00
3
0.02
30.
013
0.02
4
0.02
1
0.01
5*
0.01
1
0.00
9*0.
006
0.00
5*0.
002
0.00
1*0.
28
0.10
RL
D0
5.5
1.4
0.
58
0.34
*0.
31
0.25
*
0.05
5
0.14
0.02
4
0.04
0.
049
0.02
*0.
006
0.01
90.
005
0.00
50.
47
0.17
RL
D10
2.8
0.6
0.
079
0.08
90.
016
0.06
7
0.00
1
0.02
8
0.00
4
0.00
9
0.00
6
0.00
9
0.00
3
0.00
7
0.00
04
0.00
10.
32
0.15
VA
Lef
tL
LD
04.
6
1.8
0.
45
0.49
0.41
0.22
*
0.07
0.13
0.08
3
0.12
0.
088
0.07
6*0.
049
0.04
6*0.
015
0.02
20.
50
0.14
LL
D10
3.1
1.0
0.
03
0.1
0.13
0.09
7*
0.00
2
0.00
90.
014
0.02
3
0.02
5
0.01
7*0.
001
0.01
30.
001
0.00
10.
43
0.17
RL
D0
3.2
0.9
0.
20
0.16
*0.
27
0.20
*
0.03
8
0.11
0.
003
0.03
0.
023
0.02
1
0.00
5
0.02
50.
007
0.00
6*0.
55
0.12
RL
D10
2.5
0.7
0.
08
0.04
*
0.01
7
0.06
7
0.01
6
0.01
2
0.00
3
0.02
0.
009
0.00
90.
01
0.00
3*0.
002
0.00
40.
27
0.08
VA
Rig
ht
LL
D0
5.5
1.7
0.
50
0.21
*0.
09
0.20
0.02
1
0.09
20.
032
0.07
3
0.02
7
0.02
0*0.
004
0.02
50.
012
0.00
8*0.
42
0.15
LL
D10
2.8
0.7
0.
22
0.04
*
0.11
0.05
*0.
018
0.03
4
0.01
1
0.01
3
0.00
7
0.00
70.
007
0.00
6*0.
001
0.00
1*0.
43
0.14
RL
D0
6.9
2.3
0.
64
0.58
*0.
27
0.35
0.
03
0.16
0.03
8
0.05
0.
084
0.05
*0.
099
0.09
2*0.
001
0.01
30.
38
0.14
RL
D10
3.3
1.7
0.
09
0.11
0.01
6
0.07
20.
018
0.04
9
0.00
7
0.01
9
0.01
0.01
20.
009
0.01
3
0.00
1
0.00
20.
23
0.1
Val
ues
are
mea
ns
SD
(n
6).*
P
0.05
com
pare
dw
ith
zero
by1-
tail
edu
npa
ired
t-te
st.
Equ
atio
n:v
aria
ble
I
ax
by
cz
dxy
eyz
fxz
gxyz
.All
inte
rcep
tsar
esi
gnifi
can
t.
759LATERAL POSTURE AND PEEP ON VA AND Q
J Appl Physiol VOL 92 FEBRUARY 2002 www.jap.org
-
Tab
leA
3.C
oeffi
cien
tsan
dR
2of
mu
ltip
leli
nea
rre
gres
sion
equ
atio
n
fit
toV
A/
Qan
dP
c O2
dat
afo
rw
hol
e,le
ft,
and
righ
tlu
ng,
resp
ecti
vely
Lu
ng
Pos
itio
nP
EE
PIn
terc
ept
ab
cd
ef
gR
2
VA/Q
Wh
ole
LL
D0
1.21
0.50
0.04
7
0.05
0.04
2
0.03
70.
019
0.02
3
0.00
1
0.00
7
0.00
5
0.00
5
0.00
2
0.00
30.
001
0.00
20.
43
0.10
LL
D10
1.10
0.24
0.01
8
0.03
20.
015
0.03
20.
011
0.01
4
0.00
3
0.00
5
0.00
2
0.00
2*0.
0000
9
0.00
20.
0000
04
0.00
10.
30
0.19
RL
D0
1.08
0.43
0.
008
0.05
60.
035
0.02
*0.
015
0.02
70.
004
0.00
3*
0.00
4
0.00
4
0.00
1
0.00
1*0.
0000
5
0.00
20.
50
0.37
RL
D10
1.25
0.32
0.03
5
0.02
7*0.
003
0.01
20.
014
0.01
7
0.00
2
0.00
4
0.00
1
0.00
30.
0000
8
0.00
20.
0001
0.00
10.
26
0.10
VA/Q
Lef
tL
LD
00.
92
0.38
0.
004
0.04
0.05
3
0.03
*0.
038
0.03
70.
013
0.02
0.
01
0.01
70.
002
0.00
5
0.00
02
0.00
30.
48
0.10
LL
D10
0.99
0.27
0.03
0.01
*0.
03
0.02
*0.
014
0.01
3
0.00
02
0.00
5
0.00
3
0.00
30.
002
0.00
3
0.00
1
0.00
1*0.
46
0.19
RL
D0
1.02
0.53
0.
15
0.06
0.04
2
0.03
60.
009
0.02
60.
013
0.01
5
0.00
1
0.00
9
0.00
3
0.00
40.
002
0.00
1*0.
54
0.20
RL
D10
1.42
0.45
0.
001
0.04
6
0.01
1
0.03
20.
013
0.01
80.
004
0.00
6
0.00
1
0.00
30.
002
0.00
60.
001
0.00
20.
21
0.11
VA/Q
Rig
ht
LL
D0
1.40
0.6
0.
022
0.03
50.
032
0.04
50.
01
0.03
20.
011
0.02
0
0.00
4
0.00
6
0.00
4
0.00
4*0.
001
0.00
20.
31
0.05
LL
D10
1.22
0.24
0.
03
0.04
5
0.01
5
0.02
20.
014
0.00
6*
0.00
2
0.00
5
0.00
1
0.00
20.
0002
0.00
30.
0003
0.00
10.
27
0.15
RL
D0
1.09
0.39
0.01
4
0.02
20.
035
0.02
2*0.
023
0.02
50.
006
0.01
1
0.00
6
0.00
60.
005
0.00
8
0.00
02
0.00
10.
48
0.09
RL
D10
1.13
0.24
0.04
0.02
*0.
012
0.01
20.
017
0.02
0.
003
0.00
7
0.00
2
0.00
30.
003
0.00
3*
0.00
034
0.00
10.
35
0.06
Pr O
2W
hol
eL
LD
011
3.4
6.7
1.30
1.2*
1.15
0.89
*0.
50
0.26
*
0.14
0.19
0.
16
0.15
*
0.06
0.05
10.
03
0.04
0.51
0.15
LL
D10
113.
8
4.2
0.43
0.82
0.45
0.8
0.33
0.23
*
0.08
0.14
0.
074
0.05
4*
0.00
4
0.04
80.
006
0.01
70.
30
0.17
RL
D0
111.
3
8.7
0.
59
1.1
1.43
0.73
*0.
59
0.70
0.20
0.23
0.
21
0.13
0.
013
0.02
80.
003
0.02
90.
57
0.09
RL
D10
113.
8
5.2
0.65
0.45
*0.
06
0.24
0.31
0.33
0.
05
0.07
0.
017
0.05
7
0.01
8
0.03
50.
004
0.01
30.
30
0.14
Pr O
2L
eft
LL
D0
104.
9
120.
21
2.4
2.8
2.6*
0.85
0.67
*0.
50
0.57
0.
42
0.50
0.07
9
0.32
0.
04
0.15
0.52
0.16
LL
D10
112.
3
6.8
0.83
0.77
*1.
07
0.85
*0.
40
0.30
*0.
05
0.13
0.
15
0.13
*0.
02
0.06
7
0.02
0.02
*0.
47
0.22
RL
D0
109.
2
12
0.61
1.0
1.98
1.7*
0.45
0.87
0.13
0.20
0.
20
0.21
0.
04
0.13
0.03
6
0.03
70.
60
0.21
RL
D10
117.
2
5.9
0.
25
0.84
0.
23
0.66
0.19
0.37
0.02
0.09
0.
025
0.05
60.
06
0.09
0.01
8
0.03
10.
24
0.12
Pr O
2R
igh
tL
LD
011
8.6
4.3
0.
25
0.36
0.55
0.57
0.2
0.3
0.17
0.23
0.
087
0.11
0.
065
0.07
80.
013
0.02
80.
35
0.14
LL
D10
117.
9
3.2
0.
75
0.76
0.
4
0.47
0.34
0.16
*
0.04
5
0.09
5
0.01
3
0.04
50.
043
0.06
60.
002
0.00
80.
30
0.15
RL
D0
112.
6
7.3
0.
03
0.4
0.88
0.64
0.67
0.55
0.19
0.16
0.
26
0.16
0.22
0.26
0.
011
0.02
50.
50
0.08
RL
D10
111.
6
4.7
0.90
0.34
*0.
23
0.34
0.44
0.49
0.
075
0.17
0.
054
0.07
40.
06
0.07
0.
007
0.01
90.
38
0.06
Val
ues
are
mea
ns
SD
(n
6).
*P
0.05
com
pare
dw
ith
zero
by1-
tail
edt-
test
.
Equ
atio
n:
Var
iabl
e
I
ax
by
cz
dxy
eyz
fxz
gxyz
.A
llin
terc
epts
are
sign
ifica
nt.
760 LATERAL POSTURE AND PEEP ON VA AND Q
J Appl Physiol VOL 92 FEBRUARY 2002 www.jap.org
-
with 10 cmH2O PEEP and inversion to the RLD pos-ture.
APPENDIX
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) orientedat the edges of the
lung. As lung volume increased withPEEP, the coordinate distances
between the center of massand original coordinate axes increased.
The increase in dis-tance was greatest (50%) in the LLD posture and
least(10%) in the RLD posture.
Regional Variation in the Spatial Gradients
The coefficients df of the independent variable xy, yz, andzx in
the linear equation (Eq. 5) are measures of the variationof the
spatial gradients in any one coordinate along anorthogonal
coordinate (Tables A2 and A3). For the whole lungwithout PEEP in
the LLD posture, the vertical gradient(Q/x) in blood flow increased
linearly with z (coefficient f,0.046)
Q/x0.27 0.046z (A1)
At y 0, the vertical blood flow gradient increase from avalue of
0.59 Q ml1 cm1 in the caudal region at z 7cm to a value of 0.05 in
the cranial regions at z 7 cm. Thusthe vertical gradient was
maximal in the caudal regions andvanished in the cranial regions.
The application of PEEPreduced this z variation of the vertical
gradient to 9% (coef-ficient f, 0.005).
Similarly, taking the left lung separately in the LLD pos-ture,
the significant coefficient e (0.074, Table 2) impliesthat the
dorsal-ventral gradient in Q also varied linearlywith z (x 0)
Q/y 0.26 0.074z (A2)
Thus the dorsal-ventral gradient decreased to 0.26 in thecranial
regions (z 7 cm) and became positive (0.78) in thecaudal regions (z
7 cm). Similar variations in otherspatial gradients were present
for both Q and VA. Variationsin the gradients in VA were
substantial only in the LLDposture without PEEP.
We thank Bill Altemeier and Wayne Lamm for helpful sugges-tions
and criticism and Ian Starr, Jenny Souders, Erin Shade,Dowon An,
Shen Sheng Wang, and Emily Anderson for excellenttechnical
assistance.
This research was supported by National Heart, Lung, and
BloodInstitute Grant HL-12174, a fellowship (to H. Chang) from
theTri-Service General Hospital at Taiwan, and a sabbatical leave
(S. J.Lai-Fook) from the University of Kentucky.
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