Effects of emboli, positive-pressure ventilation, and airway water on lung water measurements

We tested the effects of microemboli, continuous positive-pressure ventilation (CPPV), and aspirated airway water on measurements of extravascular lung water by use of the technique of thermal indicator dilution (ETVL). A control group of dogs and a group of dogs in which dextran was infused created all levels of pulmonary edema. In an emboli group 0.125 g/kg of starch microemboli (63-74 micron diam) were infused. In groups with emboli and CPPV, starch emboli were infused and CPPV was then applied at 15 cmH2O. In an airway saline group measured amounts of saline were poured into the airway. In all groups postmortem pulmonary extravascular tissue weight (PETW) was determined and compared with the last ETVL. Emboli created an increased scatter when the last ETVL is compared with PETW because 1) blood trapped distal to emboli was included in the ETVL measurement, and/or 2) diffusion limitations for the thermal indicator were exceeded. Emboli and CPPV decreased ETVL/PETW. Airway saline (80 +/- 5%) was measured by ETVL. In conclusion, the ETVL technique is reliable in well-perfused lungs but loses accuracy in measuring lung water after emboli of any size or with large amounts of airway fluid.     

Effects of continuous positive-pressure ventilation in experimental pulmonary edema.

We compared the effects of continuous positive-pressure ventilation (CPPV), using 10 cmH2O positive end-expiratory pressure (PEEP), with intermittent positive-pressure ventilation (IPPV), on pulmonary extravascular water volume (PEWV) and lung function in dogs with pulmonary edema caused by elevated left atrial pressure and decreased colloid osmotic pressure. The PEWV was measured by gravimetric and double-isotope indicator dilution methods. Animals with high (22-33 mmHg), moderately elevated (12-20 mmHg), and normal (3-11 mmHg) left atrial pressures (Pla) were studied. The PEWV by both methods was significantly increased in the high and moderate Pla groups, the former greater than the latter (P less than 0.05). There was no difference in the PEWV between animals receiving CPPV and those receiving IPPV in both the high and moderately elevated Pla groups. However, in animals with high Pla, the Pao2 was significantly better maintained and the inflation pressure required to deliver a tidal volume of 12 ml/kg was significantly less with the use of CPPV than with IPPV. We conclude that in pulmonary edema associated with high Pla, PEEP does not reduce PEWV but does improve pulmonary function.     

Effect of negative-pressure ventilation on lung water in permeability pulmonary edema

We have previously shown (Am. Rev. Respir. Dis. 136: 886-891, 1987) improved cardiac output in dogs with pulmonary edema ventilated with external continuous negative chest pressure ventilation (CNPV) using negative end-expiratory pressure (NEEP), compared with continuous positive-pressure ventilation (CPPV) using equivalent positive end-expiratory pressure (PEEP). The present study examined the effect on lung water of CNPV compared with CPPV to determine whether the increased venous return created by NEEP worsened pulmonary edema in dogs with acute lung injury. Oleic acid (0.06 ml/kg) was administered to 27 anesthetized dogs. Supine animals were then divided into three groups and ventilated for 6 h. The first group (n = 10) was treated with intermittent positive-pressure ventilation (IPPV) alone; the second (n = 9) received CNPV with 10 cmH2O NEEP; the third (n = 8) received CPPV with 10 cmH2O PEEP. CNPV and CPPV produced similar improvements in oxygenation over IPPV. However, cardiac output was significantly depressed by CPPV, but not by CNPV, when compared with IPPV. Although there were no differences in extravascular lung water (Qwl/dQl) between CNPV and CPPV, both significantly increased Qwl/dQl compared with IPPV (7.81 +/- 0.21 and 7.87 +/- 0.31 vs. 6.71 +/- 0.25, respectively, P less than 0.01 in both instances). CNPV and CPPV, but not IPPV, enhanced lung water accumulation in the perihilar areas where interstitial pressures may be most negative at higher lung volumes.     

Expiratory muscle activity during pulmonary edema in the anesthetized dog.

The present study evaluated the reflex response of the expiratory muscles to pulmonary congestion and edema. The electromyograms of two thoracic and four abdominal expiratory muscles were recorded in 12 anesthetized dogs. Pulmonary edema was induced by rapid saline infusion in six dogs and injection of oleic acid into the pulmonary circulation in the remaining six dogs. Both forms of pulmonary edema reduced pulmonary compliance, interfered with gas exchange, and induced a rapid and shallow breathing pattern. The electrical activity of all abdominal muscles was suppressed during both forms of pulmonary edema. In contrast, the electromyogram activity of the thoracic expiratory muscles was not significantly affected by pulmonary edema. Acute pulmonary arterial hypertension produced in two dogs by inflating a balloon in the left atrium had no effect on ventilation or expiratory muscle electrical activity. In two vagotomized dogs, pulmonary edema did not inhibit the expiratory muscles. We conclude that pulmonary edema suppresses abdominal but not thoracic expiratory muscle activity by vagal reflex pathway(s). Extravasation of fluid into the lung appears to be more important than an increase in pulmonary vascular pressure in eliciting this response.     

Effect of lung volume on pulmonary mechanics in guinea pigs

The lung volume (VL) dependence of several dynamic pulmonary mechanical properties of the guinea pig lung were determined over the range of the vital capacity (10-100% VC) with the vagi intact and sectioned. We found dynamic compliance to be strongly VL dependent, decreasing as much as 85% between functional residual capacity (FRC) and total lung capacity (TLC). Below FRC, dynamic compliance either remained unchanged or decreased, depending upon the technique used in its measurement. Pulmonary resistance (RL) decreased monotonically with increasing VL, whereas pulmonary conductance was linearly related to VL. Conductance was much less sensitive to VL than compliance, increasing only 28% between FRC and TLC. The sensitivity of pulmonary conductance to VL was substantially increased by subtracting the resistance of the tracheal cannula from RL. Specific pulmonary conductance was not independent of VL but decreased approximately 45% over the range of the VC. Pulmonary inertance was found to be unaffected by VL. Extrapolation from these data indicate that small differences in FRC, which might be expected within and between studies relying on pulmonary mechanical measurements, would most strongly affect compliance estimates and only moderately alter resistance estimates. It also indicates that the use of specific pulmonary conductance does not remove VL as an independent variable.     

Morphological and physiological responses of the lungs of dogs to acute decompression

The lung's response to decompression was studied in dogs anesthetized with pentobarbital sodium. Arterial pressure, hematocrit, right ventricular pressure, left ventricular end-diastolic pressure (LVEDP), dynamic compliance (CL), pulmonary resistance (RL), and arterial PO2, PCO2, and pH were measured prior to and for 3 h after a simulated air dive to 300 feet of seawater. Bronchoscopy was performed predive and at 3 h postdive. At 3 h animals were killed, and sections of lung were excised for histological examination. The decompression profile used regularly produced pulmonary hypertension, systemic hypotension, hemoconcentration, and arterial hypoxemia. CL fell in all but one dived animal. RL was more variable but remained unchanged postdive in most animals. The decompression stress did not alter the bronchoscopic and histological appearance of the airway mucosa. Pulmonary edema was regularly observed in histological sections and occurred without elevations of LVEDP. We concluded that noncardiac pulmonary edema is the principal response of the lung to decompression stress.     

Pulmonary mechanics during the ventilatory response to hypoxemia in the newborn monkey

Dynamic lung compliance (CL), inspiratory pulmonary resistance (RL), and functional residual capacity (FRC) were measured in 10 unanesthetized 48 h-old newborn monkeys and seven 21-day-old infant monkeys during acute exposures to an equivalent level of hypoxemia. End-expiratory airway occlusions were performed and the pressure developed by 200 ms (P0.2) was utilized as an index of central respiratory drive. P0.2 demonstrated a sustained increase throughout the period of hypoxemia on day 2 despite the fact that minute ventilation (VI) initially increased but then fell back to base-line levels. Dynamic lung compliance fell and FRC increased by 5 min of hypoxemia in the newborns. The 21-day-old monkeys exhibited a sustained increase in both VI and P0.2 throughout the hypoxic period with no change in CL and FRC. RL did not change at either postnatal age during hypoxemia. These data indicate that the neonatal monkey is subject to changes in pulmonary mechanics (decreased CL and increased FRC) during hypoxemia and that these changes are eliminated with maturation.     

Hypoxemia and low Crs in vagally denervated lambs result from reduced lung volume and not pulmonary edema.

Vagal denervation performed in the intrathoracic region in newborn lambs leads to hypoxemia and decreased respiratory system compliance (Crs), which could result from atelectasis and/or pulmonary edema. The objective of the present study was to quantify the relative roles of alveolar derecruitment and pulmonary edema as underlying cause(s) of respiratory failure. Vagal denervation was performed in the intrathoracic region and below the recurrent laryngeal nerves in six newborn lambs within 24 h of birth, whereas six were sham operated. Pre- and postinflation Crs was measured to investigate the presence of alveolar derecruitment. Pulmonary edema was assessed with lung wet-dry-to-wet and lung tissue wet-to-dry ratios, total protein, and FITC-BSA recovery in lung tissue and bronchoalveolar lavage. Compared with that in the sham-operated animals, Crs was significantly lower in vagally denervated animals. However, postinflation, pulmonary system compliance obtained by quasi-static lung inflation and deflation to 30 cmH2O showed no significant difference between the sham-operated and denervated lambs. The lung wet-dry-to-wet and lung tissue wet-to-dry ratios, total protein, and FITC-BSA recovery in lung tissue and bronchoalveolar lavage were similar in denervated and sham-operated groups. We provide evidence that reduced lung volume and not pulmonary edema is associated with intrathoracic vagal denervation and is the likely underlying mechanism for hypoxemia and low Crs.     

Direct injury to the bronchial vasculature in anesthetized sheep.

Injury to the bronchial vasculature may contribute to liquid and solute leakage into the lung during noncardiac pulmonary edema. The purpose of this study was to measure changes in hemodynamics, pulmonary mechanics, extravascular lung water, and lung morphometry after selectively injuring the bronchial vasculature in anesthetized sheep. In two groups of seven sheep, we injected oleic acid (0.1 ml/kg) or normal saline directly into the bronchoesophageal artery. We measured systemic and pulmonary arterial pressures, cardiac output, oxygen saturation, pulmonary resistance and compliance, and lung volumes before and 1 and 4 h after injection. The lungs were removed for measurement of extravascular water, histology, and morphometry. Four hours after injection of oleic acid, cardiac output decreased but pulmonary arterial pressure did not change. In addition, pulmonary resistance increased and dynamic compliance and vital capacity decreased. Extravascular lung water was slightly but significantly greater in the oleic acid group. Histological examination showed interstitial edema and leukocytes in airway walls and sloughing of bronchial epithelium but little or no alveolar edema. Morphometric analysis showed significant thickening of airway walls. We conclude that direct injury to the bronchial vasculature increases lung resistance, decreases dynamic compliance, and increases extravascular lung water by the accumulation of an inflammatory infiltrate in airway walls.     

High surface tension pulmonary edema induced by detergent aerosol

The effect of the detergent dioctyl sodium sulfosuccinate on pulmonary extravascular water volume (PEWV) was studied in adult anesthetized mongrel dogs. The detergent was dissolved as a 1% solution in a vehicle of equal volumes of 95% ethanol and normal saline and administered by ultrasonic nebulizer attached to the inspiratory tubing of a piston ventilator. Two hours following detergent aerosol PEWV measured gravimetrically was increased compared with either animals receiving no aerosol or those receiving an aerosol of vehicle alone. Loss of surfactant activity and increased alveolar surface tension were demonstrated by Wilhelmy balance studies of minced lung extracts, by a fall in static compliance, and by evidence of atelectasis and instability noted by gross observation and by in vivo microscopy. No significant changes in colloid oncotic pressure or pulmonary microvascular hydrostatic pressure were observed. These data suggest that pulmonary edema can be induced by increased alveolar surface tension and support the concept that one of the major roles of pulmonary surfactant is to prevent pulmonary edema.     

The ischemic lung: Role of the bronchial arteries in lung function

A patient with a dissecting aortic aneurysm, Type 1, developed acute pulmonary edema unexplained by the usual etiologic factors. Pathologic evidence that bronchial arterial circulation was interrupted led us to hypothesize that pulmonary edema could be due to ischemia of the bronchial circulation. To test this hypothesis, two chronic studies were done in dogs. The first study consisted of selective ligation of the right posterior bronchial artery at its origin at the fifth or sixth intercostal artery. After recovery from surgery, biopsies were taken from the ipsilateral and contralateral lung at time periods from 5 hours to 11 days. Ischemic damage was found in seven of eight dogs (87.5%), and was confined to the right lung. Histological examination revealed initial congestion within 8 hours, followed by pulmonary edema within 72 hours, and finally, disruption of alveolar septa with small emphysematous bullae on the eleventh postoperative day. The left lung remained normal in histological appearance. The second study consisted of transplanting the bronchial artery to the pulmonary artery to create a low pressure system and low O(2) content, and to simulate a regional shock situation. In five of six dogs (83.3%), the anastomosis was occluded within 72 hours, probably due to pressure competition from small collateral bronchial circulation. However, in these five dogs, pulmonary vascular resistance increased by 53%, intrapulmonary shunting increased by 83%, and the alveolar-to-arterial oxygen gradient increased by 150 mm Hg. Pulmonary edema was again confined to the right lung. Bronchial arteriograms demonstrated the extensive and variable distribution of the bronchial circulation in dogs. In the sixth dog, the anastomosis remained patent with a left-to-right shunt, due to a larger bronchial arterial collateral circulation. In this animal, the pulmonary arterial resistance, intrapulmonary shunting, and alveolar-arterial O(2) gradient were normal. Pulmonary edema was absent in lung biopsies. Bronchial circulation is discussed with respect to its clinical implications for lung transplants, shock, thoracic aneurysms, and mediastinal surgery. The results of this study suggest that the systemic bronchial circulation is important for normal lung function.     

Respiratory failure after endotoxin infusion in sheep: lung mechanics and lung fluid balance

Infusion of Escherichia coli endotoxin (0.12-1.5 micrograms/kg) into unanesthetized sheep causes transient pulmonary hypertension and several hours of increased lung vascular permeability, after which sheep recover. To produce enough lung injury to result in pulmonary edema with respiratory failure, we infused larger doses of E. coli endotoxin (2.0-5.0 micrograms/kg) into 11 chronically instrumented unanesthetized sheep and continuously measured pulmonary arterial, left atrial and aortic pressures, dynamic lung compliance, lung resistance, and lung lymph flow. We intermittently measured arterial blood gas tensions and pH, made interval chest radiographs, and calculated postmortem extravascular bloodless lung water-to-dry lung weight ratio (EVLW/DLW). Of 11 sheep 8 developed respiratory failure; 7 died spontaneously 6.3 +/- 1.1 h, and one was killed 10 h after endotoxin infusion. All sheep that had a premortem room air alveolar-arterial gradient in partial pressure of O2 (PAo2-Pao2) greater than 42 Torr (58 +/- 5 (SE) Torr) died. Of eight sheep that had radiographs made, six developed radiographically evident interstitial or interstitial and alveolar edema. Pulmonary artery pressure rose from base line 22 +/- 2 to 73 +/- 3 cmH2O and remained elevated above baseline levels until death. There was an initial fourfold decrease in dynamic compliance and sixfold increase in pulmonary resistance; both variables remained abnormal until death. EVLW/DLW increased with increasing survival time after endotoxin infusion, suggesting that pulmonary edema accumulated at the same rate in all fatally injured sheep, regardless of other variables. The best predictor of death was a high PAo2-Pao2. The marked increase in pulmonary resistance and decrease in dynamic compliance occurred too early after endotoxin infusion (15-30 min) to be due to pulmonary edema. The response to high-dose endotoxin in sheep closely resembles acute respiratory failure in humans following gram-negative septicemia. Respiratory failure and death in this model were not due to pulmonary edema alone.     

Microvascular membrane permeability in high surface tension pulmonary edema

Pulmonary edema was induced in dogs by an aerosol of detergent dioctyl sodium sulfosuccinate. The permeability of the pulmonary microvascular membrane was assessed by cannulating an afferent tracheobronchial lymphatic and comparing the lymph-to-plasma total protein concentration (CL/CP) during high lymph flows induced by increasing left atrial (LA) pressure after detergent aerosol. Base-line CL/CP of 0.69 +/- 0.02 fell to 0.55 +/- 0.03 with increased LA pressure alone. CL/CP fell to 0.47 +/- 0.02 when LA pressure was increased following detergent, 0.51 +/- 0.04 following an aerosol of the vehicle in which the detergent was dissolved, and 0.73 +/- 0.10 following intravenous alloxan. In additional animals protein concentration of the airway edema fluid was compared with that of plasma. The ration of protein concentration of airway fluid to plasma was 0.63 +/- 0.08 following detergent aerosol, 0.64 +/- 0.10 following increased LA pressure, and 0.94 +/- 0.09 following administration of alloxan. These data indicate no major increase in pulmonary microvascular permeability following detergent aerosol and support the concept that pulmonary edema is the consequence of reduced interstitial perimicrovascular hydrostatic pressure caused by increased alveolar surface tension.     

"Closing volume" changes in alloxan-induced pulmonary edema in anesthetized dogs.

"Closing volume" (CV) was measured by the single-breath oxygen (SBO2) test in six dogs (alloxan group) before and after alloxan 100-200 mg/kg iv) was injected. CV increased significantly (P less than 0.05) from 32 +/- 3.2% (base line) to 45 +/- 3.5 % in period 1 (0-30 min after alloxan), but vital capacity (VC), respiratory system pressure volume (PV) curves, and alveolar plateau slopes did not change. No radiologic evidence of pulmonary edema was demonstrated in two dogs studied in period 1. CV decreased to 20 +/- 3.9% during period 2 (30-80 min after alloxan) and was associated with tracheal frothing, decreased VC, changes in the PV curve, and alveolar plateau slope, as well as histologic evidence of severe pulmonary edema. CV was 29 +/- 3.0%, and there were no changes in VC, PV curves, or alveolar plateau slopes in 6 other dogs studied for 2 h (control group). CV increased during period 1 before pulmonary edema could be demonstrated by changes in VC, PV curves, or radiography, but in period 2 lung function was so altered that CV by the SBO2 technique gave no useful information.     

Relation of pressure and flow of pulmonary circulation in patients with chronic obstructive pulmonary disease

A series of 31 patients with various degrees of chronic obstructive pulmonary disease underwent right heart catheterization using flow-directed thermodilution catheters. Both rest and supine exercise values were obtained. The patients were divided into two groups on the basis of their reduction in forced expiratory volume in 1 s (FEV1). In patients with FEV1 values of greater than or equal to 1,300 ml (group 1), the arterial oxygen partial pressure (PaO2) did not significantly change with exercise, while in patients with FEV1 of less than or equal to 1,200 ml (group 2) PaO2 significantly (p less than 0.05) fell in response to exercise. In group 2, a significant increase of total pulmonary resistance (TPR) with exercise was found (p less than 0.01). Pulmonary vascular resistance (PVR) remained unchanged in both subgroups. It is suggested that the value of PVR for subgroup 2 is artificially low because an important variable, namely pulmonary artery wedge pressure, is influenced by alveolar pressure in patients with an uneven distribution of perfusion and ventilation at pulmonary venous pressures lower than alveolar pressure. The steeper slope of the pressure-flow relationship in these patients is probably due to an increased vascular tone caused by chronic hypoxia at rest and further fall of PaO2 and rise of arterial CO2 partial pressure in response to exercise.     

Characteristics of the pulmonary transport functions for heat and dye in pulmonary edema and orthostasis

The aim of this study was to investigate whether changes in the distribution of pulmonary blood flow and disturbances of the pulmonary microcirculation can be detected by use of inflow-outflow indicator-dilution measurements. In 18 anesthetized (N2O-piritramide) mongrel dogs 221 thermal-indocyanine green dye indicator dilution kinetics were recorded in the pulmonary artery and aorta after central venous indicator injection. The lagged normal density function was used as a model for the pulmonary transport functions for heat and dye. The parameters of the lagged normal density function were computed by a non-linear least squares procedure by iterative convolution. After baseline measurements, in nine dogs, pulmonary edema was induced by central venous application of oleic acid. In nine other dogs, measurements were performed before and after postural changes. Our data show that both the microvascular injury caused by oleic acid edema and the perfusion heterogeneity caused by orthostasis can be detected by the indicator dilution technique since the both relative dispersion and skewness of the transport functions for heat and dye were significantly increased after these interventions.     

Does interstitial lung edema compress airways and arteries? A morphometric study

We compared areas and diameters of small airways and arteries in three groups of anesthetized dogs: 1) control (n = 5), 2) hydrostatic edema induced by fluid overload (n = 13), and 3) increased permeability edema induced with alpha-naphthylthiourea (n = 5). We measured pulmonary arterial and wedge pressures in all groups and cardiac output in the hydrostatic edema group. Postmortem, lobes were frozen at functional residual capacity and samples taken for measurements of extravascular lung water (Qwl/dQl) and for light microscopy. We also examined lobes from hydrostatic edema experiments fixed at transpulmonary pressures of 5 and 27 cmH2O. From the histology slides, bronchovascular bundles with respiratory bronchioles (n = 706) and bronchioles (n = 467) were photographed and airway and vessel areas and diameters measured. Alveolar and airway luminal edema were graded. We found that only in hydrostatic edema, pulmonary arterial and wedge pressures increased and vascular resistance fell with fluid infusion. Mean Qwl/dQl values were 3.80 +/- 0.17, 6.81 +/- 0.96, and 9.34 +/- 0.62 (SE) in control, hydrostatic, and increased permeability edema groups, respectively. By quantitative histology, airway and arterial areas and diameters did not decrease in edema and rose with increasing transpulmonary pressure. Variable quantities of air-space edema were seen. We conclude that interstitial edema does not compress small airways or arteries and that other mechanisms, including alveolar and airway luminal edema, may explain reported increases in airway resistance.     

Effect of regional alveolar hypoxia on permeability pulmonary edema formation in dogs

We studied the effects of regional alveolar hypoxia on permeability pulmonary edema formation. Anesthetized dogs had a bronchial divider placed so that the left lower lobe (LLL) could be ventilated with a hypoxic gas mixture (HGM) while the right lung was continuously ventilated with 100% O2. Bilateral permeability edema was induced with 0.05 ml/kg oleic acid and after 4 h of LLL ventilation with an HGM (n = 9) LLL gross weight was 161 +/- 13 (SE) g compared with 204 +/- 13 (SE) g (P less than 0.05) in the right lower lobe (RLL). Bloodless lobar water and dry weight were also significantly lower in the LLL as compared with the RLL of the study animals. In seven control animals in which the LLL fractional inspired concentration of O2 (FIO2) was 1.0 during permeability edema, there were no differences in gravimetric variables between LLL and RLL. In eight additional animals, pulmonary capillary pressure (Pc), measured by simultaneous occlusion of left pulmonary artery and vein, was not significantly different between LLL FIO2 of 1.0 and 0.05 either before or after pulmonary edema. We conclude that, in the presence of permeability pulmonary edema, regional alveolar hypoxia causes reduction in edema formation. The decreased edema formation during alveolar hypoxia is not due to a reduction in Pc.     

Effects of cardiac oscillations and lung volume on acinar gas mixing during apnea

We evaluated the importance of cardiogenic gas mixing in the acini of 13 dogs during 2 min of apnea. 133Xe (1-2 mCi in 4 ml of saline) was injected into an alveolar region through an occluded pulmonary artery branch, and washout was measured by gamma scintillation scanning during continued occlusion or with blood flow reinstated. The monoexponential rate constant for Xe washout (XeW) was -0.4 +/- 0.08 (SE) min-1 at functional residual capacity (FRC) with no blood flow in the injected region. It decreased by more than half at lung volumes 500 ml above and 392 ml below FRC. With intact pulmonary blood flow, XeW was -1.0 +/- 0.08 (SE) min-1 at FRC, and it increased with decreasing lung volume. However, if calculated Xe uptake by the blood was subtracted from the XeW measured with blood flow intact, resulting values at FRC and at FRC + 500 ml were not different from XeW with no blood flow. Reasonable calculation of Xe blood uptake at 392 ml below FRC was not possible because airway closure, increased shunt, and other factors affect XeW. After death, no significant XeW could be measured, which suggests that XeW caused by molecular diffusion was small. We conclude that 1) the effect of heart motion on the lung parenchyma increases acinar gas mixing during apnea, 2) this effect diminishes above or below FRC, and 3) there is probably no direct effect of pulmonary vascular pulsatility on acinar gas mixing.     

Pulmonary injury in rats following continuous exposure to 60% O2 for 7 days

Morphological, biochemical, and physiological studies were done on rats exposed to 60% O2 for 7 days. This exposure did not induce O2 tolerance but instead caused a significant decrease in survival time of animals subsequently exposed to pure O2. The activity of lung superoxide dismutases and glucose-6-phosphate dehydrogenase were unchanged after exposure to 60% O2. A decrease in lung compliance was suggested by changes in the total lung capacity and in the pressure-volume curves of excised lungs. Ventilation of these animals with large tidal excursion resulted in pulmonary edema. Morphometric analyses revealed a significant decrease in alveolar air volume and an increase in the number of alveolar macrophages. The most significant lesions involved the pulmonary vascular bed. The volume and thickness of the capillary endothelium was decreased. There were focal areas of pericapillary fluid accumulations, and a number of the smaller vessels had perivascular edema. These findings suggest that significant pulmonary injury occurs in rats exposed to 60% O2 and that the primary site of injury is the pulmonary capillary endothelium.