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(Radiology. 2001;219:724-731.)
© RSNA, 2001

Experimental Studies

Oleic Acid-induced Lung Injury: Thin-Section CT Evaluation in Dogs1

Pietro Scillia, MD, Sophia Abdel Kafi, MD, Christian Mélot, MD, PhD, Caroline Keyzer, MD, Robert Naeije, MD, PhD and Pierre Alain Gevenois, MD, PhD

1 From the Department of Radiology (P.S., C.K., P.A.G.) and the Laboratory of Physiology (S.A.K., C.M., R.N.), Erasme University Hospital, University of Brussels, Route de Lennik, 808-1070 Brussels, Belgium. Received February 10, 2000; revision requested March 24; final revision received September 6; accepted September 19. Address correspondence to P.S. (e-mail: pscillia@ulb.ac.be).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To validate lung attenuation measurements for quantifying extravascular lung water in oleic acid–induced pulmonary edema, compare subjective assessment with attenuation measurements, and compare this permeability-type pulmonary edema with hydrostatic-type pulmonary edema.

MATERIALS AND METHODS: Thin-section computed tomography (CT) and pulmonary hemodynamic examinations were performed sequentially in six dogs before and after intravenous administration of 0.08 mg of oleic acid per kilogram of body weight. Extravascular lung water and pulmonary capillary pressure were measured. Results were compared with those reported in a canine model of hydrostatic edema.

RESULTS: Oleic acid induced a progressive increase in extravascular lung water without a change in capillary pressure, which indicated pure permeability-type edema. Ground-glass opacification was detected as soon as extravascular lung water increased. Lung attenuation was highly correlated to extravascular lung water (r = 0.76, P < .001), as in hydrostatic edema, but was characterized by an almost absent gravitational gradient.

CONCLUSION: Thin-section CT is sensitive for early detection and quantification of oleic acid–induced pulmonary edema in a canine model. Different from early canine hydrostatic edema, which is characterized by a gravitational gradient, early oleic acid–induced pulmonary edema in a supine dog is characterized by nearly homogeneous distribution, except for ventral sparing.

Index terms: Animals • Computed tomography (CT), thin-section, 63.12111, 65.12111 • Lung, CT, 63.12111, 65.12111 • Lung, edema, 60.781 • Lung, function, 60.781 • Respiratory distress syndrome, adult (ARDS), 60.781


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Acute respiratory distress syndrome (ARDS) is a clinical condition characterized by increased pulmonary vascular permeability, which results in increased extravascular lung water and hypoxemia (1). Thin-section computed tomography (CT) in patients who have ARDS shows ground-glass opacification and consolidation (2–4). These aspects have been subjectively quantified in several studies (5–7). Since subjective CT quantification may be subject to overestimation (8–11), software for objective measurement of lung attenuation has been developed (12–14). We have previously used such software in a canine model of hydrostatic pulmonary edema (15). In that study, ground-glass opacification was apparent as soon as extravascular lung water increased, and attenuation measurements provided a valid quantitative estimate of the severity of lung edema.

The present study was designed to investigate the thin-section CT correlates of hemodynamics and extravascular lung water in the early stages of ARDS, which was induced in a controlled fashion in dogs after injecting oleic acid (16). The specific aims were (a) to validate lung attenuation measurement as an objective method for quantifying extravascular lung water in ARDS, (b) to compare subjective assessment with attenuation measurements, and (c) to compare the results obtained for this permeability-type pulmonary edema with those previously reported for a similar canine preparation of hydrostatic-type pulmonary edema (15).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Experimental Setting
Animal preparation.—Six adult mongrel dogs (Van Gucht, Liedekerke, Belgium) with a mean weight of 26 kg and a weight range of 17–35 kg were anesthetized with intravenous administration of 25 mg of pentobarbital sodium (Nembutal; Sanofi, Paris, France) per kilogram of body weight, paralyzed with intravenous administration of 0.2 mg/kg of pancuronium bromide (Pavulon; Organon Teknika, Boxtel, the Netherlands), and received ventilation through a cuffed endotracheal tube by using a ventilator with a servomechanism (Elema 900 B; Siemens Elema, Solna, Sweden). The inspired fraction of oxygen was 0.4; the respiratory rate, 12 breaths per minute; and the tidal volume, 10–15 mL/kg, which was adjusted to obtain an arterial partial pressure of carbon dioxide of 35–45 mm Hg. The pentobarbital sodium (25 mg/kg) and pancuronium bromide (0.2 mg/kg) were administered hourly to maintain anesthesia and prevent spontaneous respiratory efforts. Throughout the experiment, normal saline solution was infused (4 mL/kg/h) into the left external jugular vein. Sodium bicarbonate (Baxter Healthcare, Deerfield, Ill) was given as required to maintain an arterial pH greater than 7.30. Body temperature was maintained at 36°–38°C by using an electric blanket.

The experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals (17), as approved by the National Research Council (National Institutes of Health) and the council of the American Physiological Society, Bethesda, Md, and were approved by the committee on the care and use of animals in research of the Brussels School of Medicine.Hemodynamic measurements.—A balloon-tipped pulmonary artery catheter (131H-7F; Baxter Healthcare, Irvine, Calif) was inserted via the right external jugular vein and positioned with pressure monitoring in a branch of the pulmonary artery to measure pulmonary arterial pressure, occluded pulmonary arterial pressure (to estimate left atrial pressure), right atrial pressure, and central temperature; to estimate effective pulmonary capillary pressure from the pressure decay curve after balloon occlusion; and to sample mixed venous blood. A polyethylene fiberoptic thermistor catheter (Cold Pulsion; Pulsion Medical Systems, Munich, Germany) was inserted into the thoracic aorta via the right femoral artery to measure cardiac output and systemic blood pressure and to sample arterial blood. Thrombus formation along the balloon catheter was prevented by intravenously injecting 100 U of sodium heparin (Heparine B; Braun, Melsungen, Germany) just before catheter insertion.

Pulmonary and systemic vascular pressures were measured with pressure transducers (Statham P50; Gould, Oxnard, Calif). The pressure transducers were zero referenced at midchest, and vascular pressures were measured at end expiration. The heart rate was determined by using a continuously monitored electrocardiographic lead. Cardiac output and extravascular lung water were determined by injecting 10 mL/kg of 0°C 0.9% sodium chloride (ICG-Pulsion; Pulsion Medical Systems) that contained 1 mg/mL of indocyanine green dye into the central circulation as a bolus, with use of the proximal port of the pulmonary artery catheter, and with computation of the thermal and green dye dilution curves from data measured by using the aortic polyethylene fiberoptic thermistor catheter (18).

Cardiac output and extravascular lung water were each calculated as the mean of two measurements. Ventilation was suspended during these measurements to avoid alveolar dispersion of the thermal indicator. Arterial and mixed venous blood gases were measured with an automated analyzer (ABL 2; Radiometer, Copenhagen, Denmark) immediately after sample acquisition and corrected for temperature.

Venous admixture (QVA/QT, where Q = cardiac output, VA = venous admixture, and T = total ventilation) was calculated with the standard formula: (capillary O2 content - arterial O2 content)/(capillary O2 content - mixed venous O2 content), with the capillary oxygen content estimated with the calculated alveolar partial pressure of oxygen and with the oxygen saturation determined from the nomogram of Rossing and Cain (19).

The colloidal osmotic pressure was measured by using an oncometer (BMT, Berlin, Germany) in a centrifuged blood sample. The pulmonary vascular pressure signals were sampled at 200 Hz by using an analog-digital converter (RTI 800; Analog Device, Norwood, Mass) and were stored and analyzed by using a personal computer (Siemens Nixdorf, Munich, Germany). Effective pulmonary capillary pressure was computed in triplicate from the pulmonary arterial pressure decay curves after inflating the balloon in the pulmonary artery. For these measurements, the dog was disconnected from the ventilator for 8 seconds. Time 0 was defined as the time at which the pulmonary arterial pressure began to deviate from the normal wave. A monoexponential curve was fitted to a data set 0.2–2.0 seconds after occlusion and was extrapolated back toward time 0 + 150 msec (20). The lag after occlusion was chosen because it was shown to correspond to the delay from the beginning of occlusion to zero flow in the capillaries (21).

Sequence of measurements.—After control data were recorded, a bolus of 0.08 mL/kg of oleic acid was administered through the proximal port of the pulmonary artery catheter. A set of measurements was obtained 5 minutes later and thereafter every 10 minutes during a total of 95 minutes. At every time point, a thin-section CT scan was obtained immediately after measurement of pulmonary arterial pressure, effective pulmonary capillary pressure, left atrial pressure, colloidal osmotic pressure, cardiac output, extravascular lung water, and blood gases. A complete set of hemodynamic and blood gas measurements was obtained in a maximum of 5 minutes. Thin-section CT was performed during a breath hold at 30-cm water plateau inspiratory pressure. It was estimated that at this level of inspiratory pressure, the animals were at total lung capacity.

Imaging
Data acquisition.—Thin-section CT scans (Somatom Plus 4C; Siemens, Erlangen, Germany) were obtained at a constant anatomic level in the lower lobes of the lungs, caudal to the heart and cranial to the diaphragm, while the dogs were in the supine position. The scanning time was 1 second, the tube current was 171 mA, and the voltage was 140 kV. Images were reconstructed by using a high-frequency algorithm. The scans were printed by using window settings appropriate for pulmonary parenchyma (window width, 1,600 HU; window level, -600 HU).Subjective assessment.—Three radiologists (P.S., C.K., P.A.G.) independently assessed the CT scans for the presence, severity, and extent of ground-glass opacification. Images were scored according to a system adapted from that of Remy-Jardin et al (22). The severity of ground-glass opacification received a score of 0 (absent) to 3 (high visual severity). The extent of ground-glass opacification received a score of 0 (absent) to 4 (>75%) in accordance with the percentage of involved lung area. Both scores were combined for a global ground-glass opacification score of 0–7 (22). All images were randomly assessed by the three readers, two of whom (P.S., P.A.G.) were skilled in thin-section CT; the third was a radiologist in training.Objective assessment.—Lung attenuation was objectively assessed by using semiautomatic software (PULMO CT; Siemens, Forchheim, Germany) (12). This software enables automatic delineation of the lung parenchyma on CT images and calculates the distribution curves of lung attenuation values (12). The threshold value to isolate the soft-tissue–lung interface is 200 HU. If certain regions were included or excluded, contours were drawn manually by one of the authors (P.S.). In our study, data obtained with this device were transferred to a personal computer for calculation of means, medians, modes, and SDs of the distribution curves.Oleic acid–induced edema versus hydrostatic pulmonary edema.—To compare the relationships between the extravascular lung water and the CT objective measurements in oleic acid-induced pulmonary edema and hydrostatic pulmonary edema, we reconsidered data from a previously published study based on a similar model (15). In addition, we measured the gravitational gradients in both models by using the software (PULMO CT; Siemens).

Statistical Analysis
All results were expressed as mean plus or minus SD. The hemodynamic data, blood gas results, parameters of distribution curves of lung attenuation values, and visual scores were compared by performing an analysis of variance for repeated measurements. When the F ratio of the analysis of variance resulted in a P value less than .05, specific comparisons were made with modified Student t tests (23). Correlations were calculated with least squares regression analysis (two-stage analysis for longitudinal data). Inter- and intraobserver agreements were assessed by calculating the Cohen {kappa} coefficient. Agreements were classified as mild ({kappa} > 0.40), good ({kappa} > 0.60), or excellent ({kappa} > 0.80) (24). Statistical significance was set at the level of P less than .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Hemodynamics and Blood Gases
Hemodynamics and blood gases at the main steps of the protocol are shown in Table 1. Oleic acid injection increased extravascular lung water, whereas cardiac output remained unchanged (Table 1). The increase in extravascular lung water was continuous and already significant 15 minutes after oleic acid injection (Fig 1). Pulmonary capillary pressure remained constant, and in the early steps of the protocol, we observed a transient decrease in occluded pulmonary arterial pressure (Fig 2). Pulmonary vascular resistance more than doubled after oleic acid injection and reached maximum at the last step of the protocol (Table 1). Pulmonary gas exchange was already altered 5 minutes after oleic acid injection, as assessed with a decreased arterial partial pressure of oxygen (Fig 1) and an increased alveolar-to-arterial partial pressure in oxygen gradient (Table 1).


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  		TABLE 1. Hemodynamics and Blood Gases

 


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  		Figure 1. Graph shows extravascular lung water (EVLW, {bullet}) and arterial partial pressure of oxygen (PaO2, {circ}). The increase in extravascular lung water was continuous and already significant 15 minutes after oleic acid injection, and the arterial partial pressure of oxygen was already altered 5 minutes after oleic acid injection. {circ} and {bullet} = mean values for the six animals, * and {star} = P < .05, as compared with baseline. Error bars = SD.

 


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  		Figure 2. Graph shows mean pulmonary artery ({circ}), effective pulmonary capillary ({square}), and occluded pulmonary artery ({bullet}) pressures. Pulmonary capillary pressure remained constant, and we observed a transient decrease in occluded pulmonary arterial pressure. {circ}, {bullet}, and {square} = mean values for the six animals, * = P < .05, as compared with baseline. Error bars = SD.

 
Relationship between Lung Attenuation and Hemodynamic Variables
Attenuation measurements are summarized in Table 2. The surface section area of lung parenchyma did not vary significantly throughout the experiment. The mean attenuation value of the lungs increased (P < .05) 5 minutes after oleic acid injection (Fig 3). Similar evolutions were observed for the median; for the mode, which increased after 35 minutes; and for the SD of the distribution of attenuation values (Table 2). The gravitational gradient ranged from 0.15 HU/cm ± 0.35 (SD) at baseline to 0.35 HU/cm ± 0.63 95 minutes after oleic acid injection, without significant change, whereas extravascular lung water increased (P = .068) (Fig 4). The correlation between mean attenuation value and extravascular lung water was significant (r = 0.76, P < .001) (Fig 5). The equation of the straight regression line calculated from the whole data set (66 points) was mean attenuation (in Hounsfield units) = 0.23 (mL) - 872 (HU) (Fig 5). The mathematic parameters characterizing the distribution curve of the attenuation values (mean, median, mode, and SD) and the hemodynamic parameters (arterial partial pressure of oxygen, QVA/QT, and alveolar-arterial partial pressure of oxygen gradient) were significantly correlated with extravascular lung water (Table 3).


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  		TABLE 2. Characteristics of Distribution of CT Lung Attenuation Values and Subjective Scores

 


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  		Figure 3. Graph shows lung attenuation (mean, {bullet}) and subjective CT scores ({circ}). The mean attenuation value of the lungs increased 5 minutes after oleic acid injection, and the thin-section CT scores differed from the baseline values 15 minutes after oleic acid injection. {circ}, {bullet} = mean values for the six animals, * and {star} = P < .05, as compared with baseline. Error bars = SD.

 


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  		Figure 4. Graph shows gravitational gradient of lung attenuation in hydrostatic pulmonary edema (15) (dashed line, {circ}) and in oleic acid-induced edema (solid line, {bullet}), as a function of extravascular lung water (EVLW). In oleic acid-induced injury, the mean gradient did not change significantly, whereas extravascular lung water increased; conversely, in hydrostatic pulmonary edema, this gradient increased linearly. {circ}, {bullet} = mean values for the six animals. Error bars = SD.

 


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  		Figure 5. Graph shows a close correlation between mean lung attenuation and extravascular lung water (EVLW). For the straight regression line, mean attenuation (in Hounsfield units) = 0.23 (mL) - 872 (HU) (r = 0.76; P < .001).

 

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  		TABLE 3. Correlations between Extravascular Lung Water and Parameters of the Lung Attenuation Values Distribution Curve, Subjective Assessments, PaO2, and QVA/QT

 
Subjective Assessment of Ground-Glass Opacification
Illustrative thin-section CT scans obtained at baseline and 15, 65, and 95 minutes (final measurement) after oleic acid injection are shown in Figure 6. Results of subjective scoring are summarized in Table 2. The interobserver agreement coefficients were 0.43–0.61 for severity and 0.43–0.57 for extent. The intraobserver agreement coefficients were 0.58–0.75 for severity and 0.62–0.65 for extent.



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  		Figure 6a. Transverse thin-section CT scans. (a) Scan obtained at baseline. (b) Scan obtained 15 minutes after oleic acid injection shows ground-glass opacification (arrows). (c) Scan obtained 65 minutes after oleic acid injection shows that, as compared with that in b, the extent and the severity of ground-glass opacification is greater. (d) Scan obtained 95 minutes after oleic acid injection (final measurement) shows that, as compared with c, there is no statistical difference (P = .08) in the global ground-glass opacification score.

 


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  		Figure 6b. Transverse thin-section CT scans. (a) Scan obtained at baseline. (b) Scan obtained 15 minutes after oleic acid injection shows ground-glass opacification (arrows). (c) Scan obtained 65 minutes after oleic acid injection shows that, as compared with that in b, the extent and the severity of ground-glass opacification is greater. (d) Scan obtained 95 minutes after oleic acid injection (final measurement) shows that, as compared with c, there is no statistical difference (P = .08) in the global ground-glass opacification score.

 


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  		Figure 6c. Transverse thin-section CT scans. (a) Scan obtained at baseline. (b) Scan obtained 15 minutes after oleic acid injection shows ground-glass opacification (arrows). (c) Scan obtained 65 minutes after oleic acid injection shows that, as compared with that in b, the extent and the severity of ground-glass opacification is greater. (d) Scan obtained 95 minutes after oleic acid injection (final measurement) shows that, as compared with c, there is no statistical difference (P = .08) in the global ground-glass opacification score.

 


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  		Figure 6d. Transverse thin-section CT scans. (a) Scan obtained at baseline. (b) Scan obtained 15 minutes after oleic acid injection shows ground-glass opacification (arrows). (c) Scan obtained 65 minutes after oleic acid injection shows that, as compared with that in b, the extent and the severity of ground-glass opacification is greater. (d) Scan obtained 95 minutes after oleic acid injection (final measurement) shows that, as compared with c, there is no statistical difference (P = .08) in the global ground-glass opacification score.

 
The thin-section CT scores for assessing the severity and extent of ground-glass opacification were different from the baseline scores 15 minutes after oleic acid injection. In other words, ground-glass opacification was visualized as soon as the increase of extravascular lung water reached statistical significance (Fig 6b). Visual assessment of ground-glass opacification was highly correlated to mean lung attenuation (r = 0.94, P < .001) and extravascular lung water (Table 3). There was no significant correlation between pulmonary artery pressure, effective pulmonary capillary pressure, or pulmonary vascular resistance and visual or objective assessment of ground-glass opacification. In all dogs, the most ventral zone of the lungs was involved by less severe ground-glass opacification (Fig 6c, 6d).

Oleic Acid–induced Edema versus Hydrostatic Pulmonary Edema
The relationships between mean lung attenuation and extravascular lung water in oleic acid–induced pulmonary edema and hydrostatic pulmonary edema (15), respectively, are shown in Figure 7. The slope of the regression line was higher in hydrostatic edema than in oleic acid–induced edema (P = .05).



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  		Figure 7. Graph shows relationship between the mean attenuation and the extravascular lung water (EVLW) in hydrostatic (15) (dashed line, {circ}) and oleic acid-induced (solid line, {bullet}) pulmonary edema. The slope of the regression line was higher in hydrostatic edema than in oleic acid-induced edema (P = .05).

 
In oleic acid–induced injury, the mean gradient was 0.15 HU/cm ± 0.35 at the first set of measurements and did not change significantly, whereas extravascular lung water increased (P = .068). Conversely, in hydrostatic pulmonary edema, this gradient increased linearly from 0.59 HU/cm ± 0.21 to 2.56 HU/cm ± 1.17 and was significantly correlated to extravascular lung water (P < .001). The relationships between the gradient and extravascular lung water in both models of edema are shown in Figure 4.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
Results of the present study show (a) that attenuation measurements on thin-section CT scans offer a valid objective method for quantifying extravascular lung water in oleic acid–induced lung injury, (b) that ground-glass opacification is detectable as soon as extravascular lung water increases, (c) that visual assessment of ground-glass opacification closely reflects the extravascular lung water but has only mild to good inter- and intraobserver agreement, and (d) that gravitational attenuation gradients are almost absent in oleic acid–induced lung injury, in contrast with those in hydrostatic pulmonary edema.

Objective Measurement of Lung Attenuation
We found an early change in attenuation values and a significant correlation between attenuation values and extravascular lung water. These results seem at variance with those reported by Hedlund et al (25) in a previous study of a similar experimental ARDS model. These authors observed the first CT signs of edema—patchy areas of increased attenuation—only 15–30 minutes after the injection of oleic acid and found no correlation between attenuation values and extravascular lung water. Hedlund et al (25) performed a limited number of measurements on 1-cm-thick sections during suspended ventilation at functional residual capacity with a positive end expiratory pressure of 5 cm of water. We performed more measurements on 1-mm-thick CT sections obtained at only one constant anatomic level during suspended ventilation at total lung capacity, as required for assessment of ground-glass opacities (26). Thus, the apparent discrepancies between the studies may be attributed to differences in method.

In the current study, the slope of the straight regression line between mean attenuation and extravascular lung water was decreased, as compared with that previously observed in hydrostatic pulmonary edema (15). This may be explained by an increase in pulmonary blood volume in hydrostatic edema. Im et al (27) reported an increased cross-sectional area of lobular arteries in hydrostatic pulmonary edema, as opposed to a decreased cross-sectional area of lobar arteries in oleic acid-induced lung injury. In our experiments, there was a decrease in pulmonary artery occluded pressure that was compatible with a decrease in pulmonary blood volume. So, at the same level of measured extravascular lung water, mean attenuation values were higher in hydrostatic pulmonary edema, in which vascular diameters are larger, than in oleic acid-induced lung injury.

It is interesting that in our canine ARDS model, the gravitational attenuation gradient was almost absent (ie, <0.5 HU/cm) during the accumulation of extravascular lung water. This finding is in keeping with findings of a study by Murata et al (28), who reported similar attenuation values in the dependent and nondependent parts of the lungs of pigs after inducing oleic-acid lung injury. However, in Murata et al’s study (28), measurements were obtained at functional residual capacity. Measurements obtained at total lung capacity, as in our study, markedly decreased differences in attenuation between dependent and nondependent lung regions (29). Lung inflation has been shown to decrease or prevent gravitational collapse of the dependent regions of injured lungs (30). In accordance with this finding, to study the effects of extravascular lung water accumulation at thin-section CT, we believe that it is essential to measure at total lung capacity. In the same methodologic optimal condition of lung inflation, we previously found a marked gravitational gradient in hydrostatic lung edema (15). Therefore, in the early stages of lung edema, an absence of gravitational gradient may indicate increased permeability rather than increased pressure in the pulmonary capillaries.

Subjective Assessment of Ground-Glass Opacification
In the present experiments, ground-glass opacification was detected as soon as extravascular lung water increased and was strongly correlated to extravascular lung water. However, inter- and intraobserver agreements were only mild to good. Ground-glass opacification is a subjective sign that corresponds to alterations of lung parenchyma that are less than the spatial resolution of thin-section CT (26). In pulmonary edema, whatever its origin, ground-glass opacification is caused by an increase in fluid volume, which is either in the vascular or extravascular compartment or in both (26,31). In the present study, ground-glass opacification was detected before any change in pulmonary artery pressure and in the presence of unchanged cardiac output and decreased left atrial pressure, which made arterial or venous dilatation unlikely.

Hemodynamics and Extravascular Lung Water
In the present study, extravascular lung water increased progressively during the 1st hour after the injection of oleic acid and thereafter tended to stabilize, in keeping with the findings of previous studies on the same experimental ARDS model (16). Extravascular lung water was measured by using the thermal and green dye dilution method. This method has been shown to be accurate (32) and reproducible (33) and has been reported to be a satisfactory measurement of extravascular lung water in permeability-type pulmonary edema (34).

Arterial partial pressure of oxygen decreased from the first measurement after oleic acid injection and was strongly correlated to extravascular lung water. However, the determinants of arterial partial pressure of oxygen are multiple and include ventilation parameters (eg, the level of positive end expiratory pressure and the fraction of inspired oxygen) and the subject’s position (2,30,35,36). Pulmonary vascular resistance increased early, but pulmonary capillary pressure did not change in relation, at least in part, to decreased left atrial pressure and the tendency of cardiac output to decrease. Pulmonary capillary pressure was measured by using the occlusion technique (20,21), which has been shown to provide a valid estimate of pulmonary capillary pressure, as measured by using the reference isogravimetric method (37). The combination of increased extravascular lung water and unchanged pulmonary capillary pressure is typical for a pure permeability-type pulmonary edema such as that in ARDS.

In conclusion, the findings of the present study were threefold. First, attenuation measurements reflect the amount of extravascular lung water in oleic acid–induced lung injury. Second, thin-section CT depicts oleic acid–induced lung injury as ground-glass opacification as soon as extravascular lung water increases; however, although well correlated with extravascular lung water, subjective assessment of lung attenuation has only moderate to good inter- and intraobserver agreement. Third, different from early canine hydrostatic edema, which is characterized by a gravitational gradient, early oleic acid–induced pulmonary edema in a supine dog is characterized by nearly homogeneous distribution, except for ventral sparing.Practical application: Our results offer the prospect of performing thin-section CT for the noninvasive detection, quantification, and characterization of both hydrostatic and permeable pulmonary edema.


   ACKNOWLEDGMENTS
 
We thank Philippe Lejeune, MD, PhD, for technical assistance.


   FOOTNOTES
 
Abbreviation: ARDS = acute respiratory distress syndrome

Author contributions: Guarantor of integrity of entire study, P.S., R.N., P.A.G.; study concepts, P.S., P.A.G.; study design, S.A.K., P.S.; literature research, P.S.; experimental studies, P.S., S.A.K., C.M., C.K., P.A.G.; data acquisition, P.S., S.A.K., C.M., C.K., P.A.G.; data analysis/interpretation, P.S., S.A.K., R.N., P.A.G.; statistical analysis, P.S., C.M.; manuscript preparation, P.S.; manuscript definition of intellectual content, P.S., R.N., P.A.G.; manuscript editing, P.S.; manuscript revision/review, R.N., P.A.G.; manuscript final version approval, all authors.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

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