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Published online before print November 18, 2004, 10.1148/radiol.2341030992
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(Radiology 2005;234:151-161.)
© RSNA, 2004

Experimental Studies

Acute Lung Injury: Effects of Prone Positioning on Cephalocaudal Distribution of Lung Inflation—CT Assessment in Dogs1

Hyun Ju Lee, MD, Jung-Gi Im, MD, Jin Mo Goo, MD, Young Il Kim, MD, Min Woo Lee, MD, Ho-Geol Ryu, MD, Jae-Hyon Bahk, MD and Chul-Gyu Yoo, MD

1 From the Department of Radiology and Clinical Research Institute, Seoul National University Hospital and the Institute of Radiation Medicine, Seoul National University Medical Research Center, 28 Yongon-dong, Chongno-gu, Seoul 110–744, Korea (H.J.L., J.G.I., J.M.G., Y.I.K., M.W.L.); and Departments of Anesthesiology (H.G.R., J.H.B.) and Internal Medicine (C.G.Y.), Seoul National University Hospital, Seoul, Korea. Received June 30, 2003; revision requested September 9; final revision received March 26, 2004; accepted April 15. Supported by 2002 General Research Fund of Seoul National University Hospital. Address correspondence to J.G.I. (e-mail: imjg@snu.ac.kr).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To quantify cephalocaudal gradient of lung inflation in acute lung injury in a dog model in prone versus supine position.

MATERIALS AND METHODS: Experiments were performed in accordance with Guide for the Care and Use of Laboratory Animals, as approved by National Research Council (National Institutes of Health), and were approved by committee on care and use of animals in research at Seoul National University Hospital. After induction of acute lung injury with intravenous injection of oleic acid, dogs were randomized to be ventilated in either prone (n = 6) or supine (n = 6) position. Spiral computed tomography (CT) and hemodynamic measurement were performed sequentially on an hourly basis. Volume and mean attenuation of lung were measured quantitatively by using software to evaluate each CT section. Cephalocaudal gradient of mean lung attenuation, distribution of gas and tissue, and alveolar expansion were assessed. Functional residual capacity and net alveolar expansion of entire lung were measured. Statistical analysis was performed with Friedman, sign, and Mann-Whitney tests.

RESULTS: Mean lung attenuation increased gradually from apex to base of lung in supine position. Thus, inflation gradient along cephalocaudal axis was found. Gas was located predominantly in upper lung, whereas tissue was dominant in lower lung in supine position. In supine group, cephalocaudal inflation gradient showed no significant change from baseline up to 4 hours. After prone positioning, cephalocaudal inflation gradient was reduced, and gas and tissue proportions became more uniform along cephalocaudal axis. In prone group, absolute values of cephalocaudal inflation gradient at time points of prone positioning for 1, 2, and 3 hours were significantly lower than baseline values (P < .05) and those in supine group (P < .05). Alveolar expansion occurred in caudal regions, and alveolar contraction occurred in cephalic regions; accordingly, net alveolar volume of entire lung was not altered significantly. Functional residual capacity was unchanged by prone positioning.

CONCLUSION: In acute lung injury, prone positioning induced more uniform distribution of gas and tissue along cephalocaudal axis by reducing cephalocaudal inflation gradient.

© RSNA, 2004


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Computed tomography (CT) can provide quantitative information on regional lung inflation and air content. The mean CT attenuation reflects regional lung inflation because the proportion of gas and tissue determines the mean CT attenuation of the lung (1–3). Moreover, the volume of gas and tissue in the lung can also be calculated by measuring CT attenuation (3,4).

The prone position has been shown to improve oxygenation dramatically in a subset of patients with acute lung injury (5–15). In a previous CT-based study, prone positioning in acute lung injury reduced the ventral-to-dorsal gradient of the mean CT attenuation, which reflected a reduced inflation gradient along the ventral-to-dorsal axis (1). Moreover, a reduction in the inflation gradient along the ventral-to-dorsal axis was believed to induce a more homogeneous aeration of the lung and improve oxygenation in patients with acute lung injury (1).

Several investigators (16–20) have suggested that improved oxygenation in the prone position is related to a more complex mechanism, including cephalocaudal redistribution of lung inflation or perfusion, change of diaphragmatic shape, and change of shape of the chest wall, besides the gravity-related ventral-dorsal redistribution of lung inflation. However, these newly suggested mechanisms have not been fully proved. To our knowledge, the cephalocaudal distribution of lung inflation in models of acute lung injury has never been assessed or quantified. In the past, the slow acquisition time of CT scanners limited quantification of cephalocaudal inflation of the entire lung, whereas the multi–detector row helical CT scanners of the present day can image the whole lung within a few seconds. Contiguous thin CT sections can be reconstructed from the apex to the lung base, giving a reliable quantification of the cephalocaudal distribution of lung inflation.

The present study was undertaken to quantify the cephalocaudal gradient of lung inflation in acute lung injury in a dog model in the prone position compared with data in the supine position.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Animal Preparation
Twelve mixed-breed male and female adult dogs (weight, 20–30 kg) were anesthetized with an intramuscular injection of 50 mg of ketamine hydrochloride (Ketalar; Yuhan Yanghang, Seoul, Korea), 20 mg of xylazine hydrochloride (Rompun; Bayer Korea, Seoul, Korea), and intravenous administration of 0.2 mg per kilogram of body weight of vecuronium bromide. Positive pressure ventilation was initiated in a constant-flow volume-cycled mode with an inspired oxygen fraction of 0.8 (Servo ventilator 900 C; Simens Elema, Solna, Sweden), a positive end-expiratory pressure (PEEP) of zero, an inspiratory to expiratory time ratio of 1:2, a tidal volume of 10 mL/kg, and a respiratory rate of 12–30 breaths per minute, which was adjusted to obtain an optimal arterial carbon dioxide partial pressure.

Tiletamine zolazepam (5 mg/kg/h) and vecuronium bromide (0.5 mg/kg/h) were administered continuously to maintain anesthesia and to prevent spontaneous respiratory efforts. Throughout the experiment, normal saline solution was infused (4 mL/kg/h) into the left external jugular vein. Sodium bicarbonate was given as required to maintain an arterial pH level of more than 7.30. Body temperature was maintained at 36°–38°C by using an electric blanket. A radiologist (H.J.L.), an anesthesiologist (H.G.R.), and four laboratory technicians performed the animal preparation cooperatively. The experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals, as approved by the National Research Council (National Institutes of Health), and were approved by the committee on the care and use of animals in research at Seoul National University Hospital.

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 and to sample mixed venous blood. An arterial catheter was also inserted in the left femoral artery to measure systemic blood pressure and sample arterial blood.

Pulmonary and systemic vascular pressures were measured by using pressure transducers, which were zero referenced at midchest. The zero reference position was maintained when the dog was turned into the prone position. Vascular pressures were measured at end expiration, and heart rate was determined by means of continuous electrocardiographic monitoring. Cardiac output was determined by administering a bolus injection of 10 mL/kg 0.9% sodium chloride into the proximal port of the pulmonary artery catheter and computing the thermal dilution curves. Arterial and mixed venous blood gases were measured by using an automated analyzer (ABL 500 Series; Radiometers, Copenhagen, Denmark) immediately after sample acquisition and correction for temperature. All hemodynamic measurements were performed by an anesthesiologist (H.G.R.).

Experimental Protocol
After recording the hemodynamic and blood gas measurements at the ventilatory settings described earlier with the dogs in the supine position, CT scanning was performed. When measurements in the normal lung were completed, oleic acid (0.09 mL/kg) (Sigma, Steinheim, Germany) was injected slowly into the right atrium via the proximal port of the pulmonary artery catheter. To produce uniform injury, the total dose of oleic acid was partitioned into three equal aliquot portions of 0.03 mL/kg. One-third of the total dose was injected sequentially with the dogs in three positions: supine, right lateral, and left lateral. For aliquot injection, each of the above positions was maintained for approximately 3 minutes before rotation to the next position. For the next 90 minutes, the animal was kept in the supine position. After the 90-minute stabilization period, hemodynamic and gas exchange measurements and CT scanning were repeated. Subsequently, a PEEP of 3 cm H2O was applied, and the dogs were randomized into two groups according to a table of random numbers. In the supine group, the dogs were kept supine for the next 4 hours, and in the prone group, the dogs were kept prone for 3 hours and were then repositioned supine and maintained in this position for 1 hour. A set of measurements, including hemodynamic measures, blood gas analysis, and CT scans, were obtained hourly in both groups. The experiment protocol required six time points in both groups; thus, six sets of measurement were available in each dog. The descriptions and abbreviations of these time points are shown in Table 1.


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  		TABLE 1. Six Time Points of Experimental Protocol

 
Acquisition of CT Data
CT scanning of the lung was performed from the apex to the posterior costophrenic sulcus by using a four-channel multi–detector row spiral CT scanner (MX 8000; Phillips, Amsterdam, the Netherlands). The technical parameters used were 2 x 6.5-mm section collimation, 16.25-mm table feed per rotation, and a 750-msec rotation time. Each scan was obtained at 190 mA and 120 kV. The thickness of each spiral CT section was 0.5 cm. CT data were obtained during an expiratory breath hold that could be maintained automatically by using a mechanical ventilator. During an expiratory breath hold, the animals were at functional residual capacity (FRC). All CT data were recorded on a compact disk for later computerized analysis.

Analysis of CT Scans
All analysis procedures of CT scans, except for evaluation of diaphragmatic shape, were performed by a radiologist (H.J.L.).

Measurement of mean attenuation and lung volume.—Measurements were performed by using commercially available software (Rapidia; 3DMED, Seoul, Korea). This software operates on a personal computer and enables automatic calculation of the mean attenuation values and volumes in a given region of interest. As a first step, a CT image was displayed on the computer screen. The left and right lung boundaries were then delineated manually by using a pen mouse, and the software automatically calculated the mean attenuation (in Hounsfield units)and the volume of the lung surrounded by the boundary. This analysis was performed on each CT section from the apex to the lowest part of the lung (costophrenic sulcus).

Calculation of cephalocaudal gradient of mean attenuation.—The cephalocaudal gradient of mean attenuation was calculated by means of the least squares method (linear regression analysis). Mean attenuation slopes of the lung were expressed as a linear function of distance as centimeters in the cephalocaudal vector.

Calculation of gas volume, tissue volume, and functional residual capacity.—On CT sections, each voxel was characterized by a CT number, expressed in Hounsfield units, which ranged from –1000 HU (air) to 0 HU (water) to 1000 HU (bone). The lung is composed of gas and tissue (tissue includes lung structures, extravascular water, blood, etc). Therefore, it is possible to compute the relative gas and tissue volumes by using the lung volume and the mean attenuation measured on the CT sections. According to analyses described previously (3,4), the volume of tissue and the volume of gas were derived by using the following equations. Tissue volume in cubic centimeters was calculated by subtracting the CT number from 1, dividing the difference by –1000, and then multiplying the quotient by the lung volume. Gas volume in cubic centimeters was calculated by dividing the CT number by –1000 and then multiplying the quotient by the lung volume.

The total lung volume was calculated by summing the gas volume and tissue volume in the entire lung. In the present study, the total lung volume was designated as the FRC, because the lung volume was measured at the end of expiration.

Calculation of alveolar expansion.—Alveolar expansion was defined as the increase in the volume of gas in the lung and was computed as the increase in gas volume divided by the FRC measured at the baseline period of the experimental protocol. As an example, alveolar expansions (expressed in percentages) at the time points of prone positioning for 1 hour (EXPp1) and prone positioning for 2 hours (EXPp2) were calculated by using the following equations: EXPp1 = (Vgp1 – Vgb)/FRCb and EXPp2 = (Vgp2 – Vgb)/FRCb, where FRCb is the FRC at baseline, Vgb is the volume of gas at baseline, Vgp1 is the volume of gas with prone positioning at 1 hour, and Vgp2 is the volume of gas with prone positioning at 2 hours. FRCb is calculated with the following equation: FRCb = Vgb + Vtb, where Vtb is the volume of tissue at baseline.

Alveolar expansion was calculated on each CT section from the apex to the lower tip of the lung and for the entire lung.

Evaluation of diaphragm shape.—On the sagittal reconstructed images obtained from contiguous CT sections, the shape of the diaphragm at the time points of prone positioning for 1 hour and supine positioning for 1 hour were compared with that at baseline by two radiologists (H.J.L., J.G.I.).

Statistical Analysis
All data are expressed as means ± 1 SD, unless specified otherwise. Comparisons between different periods were performed by using the Friedman test. When the Friedman test resulted in a P value of less than .05, comparison between two different periods was performed by using the sign test. Comparisons between the prone and supine group were performed by using the Mann-Whitney test. Statistical analysis was performed by using SPSS 10.0 software (SPSS, Chicago, Ill). The significance level was fixed at .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Hemodynamic Variables and Blood Gases
Hemodynamic variables and blood gas levels at each time point of the protocol are summarized in Table 2. After oleic acid injection, the cardiac output remained unchanged, and the pulmonary arterial occluded pressure showed small fluctuations ranging from 7.3 mm Hg ± 1.6 to 10.8 mm Hg ± 0.8. Mean pulmonary arterial pressure increased steadily from 14.7 mm Hg ± 1.6 to 24.0 mm Hg ± 3.9 in the prone group and from 16.3 mm Hg ± 1.1 to 26.2 mm Hg ± 0.6 in the supine group. The arterial partial pressure of carbon dioxide showed a variable increase. Static respiratory compliance decreased after oleic acid injection from 31.1 mL/cm H2O ± 1.2 to 19.3 mL/cm H2O ± 2.4 in the prone group and from 40.5 mL/cm H2O ± 4.5 to 19.3 mL/cm H2O ± 1.7 in the supine group. With the exception of the arterial partial pressure of oxygen, the respiratory and hemodynamic variables showed no statistically significant difference between the two groups (Table 2).


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  		TABLE 2. Hemodynamic Variables and Blood Gases

 
Arterial oxygenation was decreased markedly after oleic acid injection. In the prone group, movement to the prone position resulted in a significant increase in oxygenation compared with baseline (P < .05) in all dogs. When the animals were repositioned in the supine position, oxygenation did not decline significantly compared with that in the prone position (P = .122). The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) in the prone group was significantly higher than that in the supine group at the time point of prone positioning for 3 hours (P = .03) (Table 2, Fig 1).



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  		Figure 1. Graph shows PaO2/FiO2 level at six time points of the protocol. In prone group, PaO2/FiO2 at time point of prone positioning for 1 hour to approximately time of return to supine positioning for 1 hour exceeded baseline value. PaO2/FiO2 in prone group was significantly higher than that of supine group at time point of prone positioning for 3 hours. * indicates P value less than .05 in comparison with baseline values. {dagger} indicates P value less than .05 in comparison with supine group at same time point. Error bars indicate standard deviations.

 
Cephalocaudal Gradient of Mean Lung Attenuation
Changes of mean lung attenuation in the cephalocaudal direction in the prone and supine groups are shown in Figure 2. The gradient of the mean lung attenuation obtained by means of linear regression analysis is presented in Table 3. In the normal lung, the mean attenuation increased gradually from the apex to the base in both groups. The gradient of the mean lung attenuation obtained at baseline was significantly larger than that obtained in the normal lung in both groups (P = .03) (Fig 2). In the normal lung and at baseline, no statistical difference in gradient was found between the prone and supine groups.



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  		Figure 2a. Graphs show mean attenuation values as a function of cephalocaudal lung level in (a) prone and (b) supine groups. In normal lung, mean attenuation increased gradually from apex to base. At baseline after oleic acid injection, mean attenuation increased at all levels, and line became steeper than that of normal lung. In prone group (a), prone positioning reversed relationship between mean lung attenuation and cephalocaudal lung height. In prone position, mean attenuation reached maximum at 10 cm above diaphragm and decreased toward the base, thus generally decreasing from apex to base. Repositioning to supine restored cephalocaudal gradient of mean attenuation to similar pattern of baseline. However, slope became gentler than baseline. In supine group (b), graph shows similar pattern to that of baseline. DD = dome of diaphragm.

 


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  		Figure 2b. Graphs show mean attenuation values as a function of cephalocaudal lung level in (a) prone and (b) supine groups. In normal lung, mean attenuation increased gradually from apex to base. At baseline after oleic acid injection, mean attenuation increased at all levels, and line became steeper than that of normal lung. In prone group (a), prone positioning reversed relationship between mean lung attenuation and cephalocaudal lung height. In prone position, mean attenuation reached maximum at 10 cm above diaphragm and decreased toward the base, thus generally decreasing from apex to base. Repositioning to supine restored cephalocaudal gradient of mean attenuation to similar pattern of baseline. However, slope became gentler than baseline. In supine group (b), graph shows similar pattern to that of baseline. DD = dome of diaphragm.

 

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  		TABLE 3. Cephalocaudal Gradients of Mean Attenuation (in Hounsfield Units) per Centimeter

 
Prone group.—Prone positioning reversed the cephalocaudal increase of lung attenuation. Mean attenuation reached a maximum 10 cm above the diaphragm and decreased toward the base, showing an overall decrease from the apex to the base (Fig 2). The absolute values of gradient at the time points of prone positioning for 1, 2, and 3 hours were significantly lower than baseline values (P < .05) and those in the supine group (P < .05) (Table 3). Return to the supine position restored the cephalocaudal increased lung attenuation pattern.

Supine group.—The cephalocaudal increased lung attenuation pattern remained unchanged, and the cephalocaudal inflation gradient showed no significant change from baseline up to the time point of supine positioning for 4 hours.

Cephalocaudal Distribution of Gas and Tissue
In the normal lung, the volume of gas was larger than the volume of tissue (Fig 3). At baseline, the volume of tissue increased and the volume of gas decreased at all levels of the lung. Gas was located predominantly in the upper lung, whereas tissue was predominant in the caudal lung regions (Fig 3). In the normal lung and at baseline, the cephalocaudal distribution of gas and tissue showed no difference between the prone and supine groups.



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  		Figure 3a. Distribution of gas and tissue along cephalocaudal axis. (a) In normal lung, volume of gas was larger than volume of tissue. (b) At baseline, volume of tissue increased and volume of gas decreased in all levels of lung. Gas was located predominantly in upper lung, whereas tissue was predominant in caudal lung regions. (c) One hour after prone positioning, compared with findings at baseline, volume of gas decreased in cephalic regions, whereas it increased in caudal regions. At the same time, lung volume below diaphragm was expanded. (d) Return to supine position restored distribution of gas and tissue to similar pattern at baseline. DD = dome of diaphragm.

 


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  		Figure 3b. Distribution of gas and tissue along cephalocaudal axis. (a) In normal lung, volume of gas was larger than volume of tissue. (b) At baseline, volume of tissue increased and volume of gas decreased in all levels of lung. Gas was located predominantly in upper lung, whereas tissue was predominant in caudal lung regions. (c) One hour after prone positioning, compared with findings at baseline, volume of gas decreased in cephalic regions, whereas it increased in caudal regions. At the same time, lung volume below diaphragm was expanded. (d) Return to supine position restored distribution of gas and tissue to similar pattern at baseline. DD = dome of diaphragm.

 


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  		Figure 3c. Distribution of gas and tissue along cephalocaudal axis. (a) In normal lung, volume of gas was larger than volume of tissue. (b) At baseline, volume of tissue increased and volume of gas decreased in all levels of lung. Gas was located predominantly in upper lung, whereas tissue was predominant in caudal lung regions. (c) One hour after prone positioning, compared with findings at baseline, volume of gas decreased in cephalic regions, whereas it increased in caudal regions. At the same time, lung volume below diaphragm was expanded. (d) Return to supine position restored distribution of gas and tissue to similar pattern at baseline. DD = dome of diaphragm.

 


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  		Figure 3d. Distribution of gas and tissue along cephalocaudal axis. (a) In normal lung, volume of gas was larger than volume of tissue. (b) At baseline, volume of tissue increased and volume of gas decreased in all levels of lung. Gas was located predominantly in upper lung, whereas tissue was predominant in caudal lung regions. (c) One hour after prone positioning, compared with findings at baseline, volume of gas decreased in cephalic regions, whereas it increased in caudal regions. At the same time, lung volume below diaphragm was expanded. (d) Return to supine position restored distribution of gas and tissue to similar pattern at baseline. DD = dome of diaphragm.

 
Prone group.—When compared with findings at baseline, the volume of gas decreased with prone positioning in the cephalic regions, whereas it increased in the caudal regions. The proportion of gas and tissue along the cephalocaudal axis was more uniform in the prone position (Fig 4). At the same time, the lung volume below the dome of the diaphragm expanded (Fig 3). Return to the supine position restored the cephalocaudal distribution of gas and tissue to the baseline pattern (Fig 3).



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  		Figure 4. Ratio of gas and tissue along cephalocaudal axis. At time point of prone positioning for 1 hour, ratio of gas and tissue was more uniform along cephalocaudal axis than at time point of supine positioning for 1 hour. DD = dome of diaphragm.

 
Supine group.—The baseline distribution was maintained up to the time point of supine positioning for 4 hours.

Cephalocaudal Distribution of Alveolar Expansion
In the prone position, alveolar expansion was observed in the caudal regions and was most prominent in lung regions below the diaphragmatic cupola (Fig 5). In the upper part of the lung, with 5–6 cm above the diaphragmatic cupola as a turning point, alveolar contraction occurred. In the supine position, a small amount of alveolar expansion at low-PEEP administration was observed in most cephalic regions of the lung (Fig 5). Alveolar contraction was not observed in the supine position.



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  		Figure 5a. Percentage of alveolar expansion along cephalocaudal axis. Zero line indicates cutoff between alveolar expansion and contraction. (a) In prone group, alveolar expansion was observed in caudal regions and was most prominent in lung regions below diaphragmatic cupola. In upper lung, with 5-6 cm above the diaphragm as a turning point, alveolar contraction occurred. (b) In supine group, alveolar expansion induced by low PEEP (3 cm H2O) occurred predominantly in cephalic lung regions. Alveolar contraction was not observed. DD = dome of diaphragm.

 


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  		Figure 5b. Percentage of alveolar expansion along cephalocaudal axis. Zero line indicates cutoff between alveolar expansion and contraction. (a) In prone group, alveolar expansion was observed in caudal regions and was most prominent in lung regions below diaphragmatic cupola. In upper lung, with 5-6 cm above the diaphragm as a turning point, alveolar contraction occurred. (b) In supine group, alveolar expansion induced by low PEEP (3 cm H2O) occurred predominantly in cephalic lung regions. Alveolar contraction was not observed. DD = dome of diaphragm.

 
Functional Residual Capacity and Alveolar Expansion of Entire Lung
As shown in Table 4, FRC was unchanged by prone positioning. In the supine group, FRC increased significantly after low-PEEP administration (P = .031).


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  		TABLE 4. Functional Residual Capacity and Alveolar Expansion in the Entire Lung

 
Alveolar expansion of the entire lung in individual dogs varied. In the prone group, it showed no significant change from baseline to the time of return to supine positioning for 1 hour. In the supine group, the alveolar expansion of the entire lung at the time points of supine positioning for 1 and 2 hours showed significant increases compared with baseline (P = .031).

Diaphragm Shape
A caudal displacement of the dorsal surface of the diaphragm at the time point of prone positioning for 1 hour relative to supine positioning at baseline was observed in all dogs in the prone group (Fig 6). All dogs in the supine group showed no visible change in the shapes of the diaphragm from baseline to the time point of supine positioning for 1 hour.



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  		Figure 6a. Sagittal reconstructions of right lung at level of inferior vena cava (left-mediastinal windows, right-lung window) obtained from contiguous CT sections in a representative dog. (a) At baseline with dog in the supine position, edematous lung tissue is located predominantly in dorsal and caudal part of lung. (b) In prone position, caudal displacement of dorsal surface of diaphragm is seen. Aeration in dorsal and caudal part of lung is improved markedly, and attenuation of entire lung is more homogeneous.

 


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  		Figure 6b. Sagittal reconstructions of right lung at level of inferior vena cava (left-mediastinal windows, right-lung window) obtained from contiguous CT sections in a representative dog. (a) At baseline with dog in the supine position, edematous lung tissue is located predominantly in dorsal and caudal part of lung. (b) In prone position, caudal displacement of dorsal surface of diaphragm is seen. Aeration in dorsal and caudal part of lung is improved markedly, and attenuation of entire lung is more homogeneous.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
This study produced four original findings. (a) An inflation gradient along the cephalocaudal axis was found in the normal lung and in acute lung injury. (b) Prone positioning in acute lung injury reduced the cephalocaudal inflation gradient and induced a more uniform distribution of gas and tissue along the cephalocaudal axis. (c) Prone positioning in acute lung injury did not alter the FRC. (d) Alveolar expansion induced by prone positioning occurred mainly at the caudal lung, but significant changes in alveolar expansion did not occur throughout the entire lung. As shown by previous studies (7,9,11), our study showed that PaO2/FiO2 in the prone position was significantly higher than that in the supine position.

The distributions of ventilation, perfusion, and lung inflation were explored by using a variety of techniques (1,16–30). In our study, we applied CT to examine changes in the distribution of lung inflation and lung air content in acute lung injury in anesthetized dogs in the prone and supine positions. Unlike the previous studies, which involved the use of a single CT section (1–4), we obtained contiguous CT sections of the entire lung by using multi–detector row spiral CT, which allowed us to determine the cephalocaudal distribution of lung inflation.

Cephalocaudal Inflation Gradient and Distribution of Gas and Tissue
In dogs with acute lung injury in the current study, the gas and tissue were distributed more evenly when the dogs were placed in the prone position than when placed in the supine position. The inflation gradient along the cephalocaudal axis decreased with the dogs in the prone position, although the values in individual animals varied. Decreased lung inflation gradient and improved arterial oxygenation occurred within 1 hour of a position change from supine to prone, and this was sustained for 3 hours. On the other hand, in supine dogs after the induction of acute lung injury, the mean CT attenuation increased markedly (ie, proportion of gas decreased) from the apex to the base. The attenuation gradient—that is, the inflation gradient along the cephalocaudal axis—was about 1.5 times that of normal gradient in supine dogs.

In healthy animals, the cephalocaudal distribution of lung inflation was investigated previously by using fluorescent microspheres and xenon CT (16,17). The normal lungs were expanded to a lesser extent at the base than at the apex, and the regional air content decreased from the apex to the base in supine animals. On the other hand, the lungs were inflated more uniformly in the prone condition. Therefore, the cephalocaudal inflation gradient was lower in prone animals than in supine animals. Our results obtained in this acute lung injury model are similar to the observations described earlier in healthy animals.

The effects of a compliant diaphragm and abdominal weight are known to be important contributors to the distribution of volume in the lung (2,31–34). In the present study, a caudal displacement of the dorsal surface of the diaphragm in the prone relative to the supine position was observed. We believe that this change of diaphragmatic configuration by means of prone positioning is one of the important factors of lung inflation gradient reduction along the cephalocaudal axis. In the supine position, the region below the diaphragm, mainly the posterior part, is more compressed by pressure exerted by the abdominal contents. These result in (a) the compression of the lower lung, which creates strong regional pleural pressure gradients, and (b) lung inflation (18,35). In contrast, in the prone position, compression by the abdominal contents is relieved, which results in a caudal displacement of the dorsal surface of the diaphragm. Therefore, the lower lung at FRC is inflated freely, and the cephalocaudal distribution of inflation becomes relatively uniform.

Improved ventilation-perfusion matching is inevitably needed for improved arterial oxygenation. Improved ventilation or perfusion alone cannot explain improved oxygenation. According to the zonal model that classically explains the distribution of pulmonary perfusion, perfusion might redistribute from the dorsal to the ventral lung regions after moving from the supine to the prone position as a result of gravitational influence (36). Paradoxically, however, a number of investigators have found that perfusion is preferentially fixed to the dorsal lung regions, regardless of body position (25,27). Accordingly, the fixed preferential distribution of perfusion to the dorsal regions, together with markedly improved dorsal lung ventilation in the prone position, produces a better ventilation-perfusion correlation and thus accounts for the improved arterial oxygenation (37). Actually, Lamm and colleagues (23) proved that when animals with acute lung injury were turned prone, the median ventilation-perfusion ratio increased, the ventral-to-dorsal (gravitational) gradient of ventilation-perfusion disappeared, and regions of shunt decreased.

It has not been studied how prone positioning in acute lung injury affects the cephalocaudal distribution of perfusion or ventilation-perfusion matching, because much attention has been focused on the ventral-to-dorsal relationship. An investigation performed in pigs with normal lungs (17) that were ventilated mechanically provided an important clue. Interestingly, the magnitude of the perfusion and ventilation gradients in the cephalocaudal direction decreased in the prone position. In the model of acute lung injury, however, the hypothesis that prone positioning equalizes the cephalocaudal distribution of perfusion and ventilation-perfusion matching has never been proved. Therefore, further investigation is needed.

In the present study, we have shown that prone positioning in acute lung injury reduces the inflation gradient along the cephalocaudal axis. If the hypothesis that prone positioning in the acute lung injury model reduces the cephalocaudal gradient of perfusion is proved in the future, the results of this study will be considered an important mechanism that explains the improvement of oxygenation with prone positioning in patients with acute lung injury.

Alveolar Expansion and Functional Residual Capacity
Our study showed that alveolar expansion in the entire lung did not show a significant change after prone positioning, although arterial oxygenation was improved significantly. Our results suggest that oxygenation improvement induced by prone positioning was not caused by overall alveolar expansion. Instead, the expansion occurs in caudal regions, which are atelectatic in the supine position, while the same amount of lung contraction occurs in cephalic regions, which are overdistended when supine.

In the current study, maintaining the supine position with low PEEP resulted in a significant increase in FRC. In the supine group, an increase of overall FRC may reflect positive alveolar expansion directly because there is no substantial redistribution of regional lung inflation. This PEEP-induced alveolar expansion occurred predominantly in cephalic regions of the lung, and this observation concurs with a previous report (38). On the other hand, placing animals in the prone position with low PEEP did not alter the FRC significantly. During an early investigation about prone positioning in acute lung injury, an increased FRC was originally suggested to be the main mechanism of oxygenation improvement (6). More recently, several experimental studies have demonstrated that the prone position does not affect the FRC (23,39). However, an increased FRC remains a possible mechanistic explanation of oxygenation improvement in the prone position because limited data are available on FRC change. Our result supports the premise that oxygenation improvement induced by prone positioning is not caused by increased FRC.

Return to Supine Positioning after Prone Positioning
When the dogs were returned to the supine position, our results showed that oxygenation did not decrease significantly when compared with prone positioning. The cephalocaudal inflation gradient after return to the supine position was significantly lower than the baseline value prior to prone positioning. This finding implies that the change in the respiratory mechanics caused by prone positioning could be preserved for 1 hour after the animals are again placed in the supine position. It also provides a piece of evidence that supports the hypothesis (40) that modifications in lung condition induced by prone positioning persist after return to the supine position.

Our study has limitations. First, our investigation is limited to the distribution of lung inflation. The effect of positioning on gas exchange may have resulted from a combination of mechanisms, including changes in regional lung inflation and the redistribution of perfusion. To confirm whether the cephalocaudal redistribution of lung inflation in acute lung injury is one of the mechanisms by which prone positioning can improve oxygenation, further correlative studies on the cephalocaudal distribution of perfusion and ventilation-perfusion matching are required. Second, we investigated only a small number of animals, so we cannot exclude a type II error in the statistics.

In conclusion, prone positioning in acute lung injury induced a reduction in the inflation gradient and a more uniform distribution of gas and tissue along the cephalocaudal axis.

Practical application: CT provides noninvasive information on lung structure and function that permits the extension of studies of lung mechanics and physiology from the whole organ to the regional level. Our study, which involved the use of multi–detector row spiral CT, adds to this armamentarium, providing a quantitative measure in cephalocaudal distribution of lung volumes and air content. The improvement of oxygenation by prone positioning is closely related to the redistribution of lung inflation and perfusion. Our study showed that prone positioning in acute lung injury induced a reduction in the inflation gradient and a more uniform distribution of gas and tissue along the cephalocaudal axis. This could be a touchstone for new explanation of oxygenation improvement.


   ACKNOWLEDGMENTS
 
The authors thank Kyoung Won Kim, MD, Chang Jin Yoon, MD, Ja Young Choi, MD, Young Ho Yoon, MD, Hyun Jung Lee, RT, Chang Ho Han, RT, Myung Sun Jang, RT, and Hyuk Jae Choi, RT, for their essential help in initiation of the experiment and for technical assistance in animal preparation.


   FOOTNOTES
 
Abbreviations: FRC = functional residual capacity, PEEP = positive end-expiratory pressure

See also Science to Practice in this issue.

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, H.J.L., J.M.G., J.G.I.; study concepts and design, H.J.L., J.M.G., J.G.I.; literature research, H.J.L., J.M.G., H.G.R., C.G.Y.; experimental studies, H.J.L., Y.I.K., M.W.L., H.G.R., J.H.B.; data acquisition, H.J.L., Y.I.K., M.W.L., H.G.R.; data analysis/interpretation, H.J.L., Y.I.K., M.W.L.; statistical analysis, H.J.L., J.M.G., J.G.I.; manuscript preparation, H.J.L., Y.I.K., M.W.L., C.G.Y., H.G.R.; manuscript definition of intellectual content, J.G.I., J.M.G., J.H.B., C.G.Y.; manuscript editing, H.J.L., J.M.G., J.G.I.; manuscript revision/review, J.M.G., J.G.I., J.H.B.; manuscript final version approval, J.M.G., J.G.I., J.H.B., C.G.Y.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
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