Regional changes in extravascular lung water detected by positron emission tomography

Regional measurements of extravascular lung water (rEVLW) were made with positron emission tomography (PET) and 15O-labeled radionuclides. The label used to measure the total lung water (TLW) content fully equilibrated with TLW prior to scanning in both dogs with normal and low cardiac outputs, and nearly so in areas of lung made edematous by oleic acid injury (the TLW values used were 97% of maximum values). Regional EVLW measurements made by PET (EVLW-PET) and gravimetric techniques in both normal and edematous lung were closely correlated (r = 0.93), and EVLW-PET increased from an average of 0.20 to 0.37 mlH2O/ml lung (P less than 0.05) after regional lung injury. PET measurements of regional blood volume always decreased [from an average of 0.12 to 0.09 ml blood/ml lung (P less than 0.05)] after cardiac output was lowered by hemorrhage in a separate set of animals. Total EVLW (by thermodye indicator dilution) did not change. Likewise, regional EVLW remained constant in areas below the left atrium but decreased in areas above the left atrium. We conclude that PET measurements are accurate, noninvasive, and reproducible and that regional changes may be detected even when measurements of total EVLW by other methods may fail to change significantly.     

Effect of regional pulmonary blood flow on extravascular lung water measurements with PET

We examined the effect of regional pulmonary blood flow (PBF) on lung water measurements made with a blood-borne label (15O-water) and positron emission tomography (PET) in five dogs. The total lung water (TLW) content of a lung region obtained at equilibrium after intravenous injection of 15O-water (TLW-water) was compared with calculations made from lung density measurements (TLW-density) also obtained with PET. These latter measurements are proportional to the tissue attenuation of radioactivity originating from an external source encircling the animal and are independent of PBF. Comparisons were made before and 60 min after oleic acid-induced injury confined to the left caudal lobe (LCL). PBF fell 61% in regions from the dorsal half of the LCL after lung injury and was unchanged on the right side. Both before and after injury, TLW-density was 10-15% higher than TLW-water. This systematic difference is probably due to overestimates of TLW-density resulting from partial volume and scattered radiation effects. When TLW-water and TLW-density were compared in 151 3-ml regions from both normal and injured lung, the disparity between the two methods of calculating TLW increased in regions with a PBF less than 0.5 ml.min-1.ml lung-1 (less than 20% of base line). However, this represented only 22% of the injured regions analyzed. Thus lung water measurements made with PET and 15O-water are accurate until regional PBF is severely reduced. With PET, such areas can be eliminated from analysis or regions can be made sufficiently large so the overall effect on the TLW measurement is minimized.     

Neutrophil depletion does not prevent lung edema after endotoxin infusion in goats

Neutropenia was produced in goats by injection of either nitrogen mustard, (1.5 mg/kg) or hydroxyurea (200 mg X kg-1 X day-1). A nitrogen mustard (M + E) group (n = 6), a hydroxyurea (H + E) group (n = 5), and a control (E) group (n = 7) were given 1-h infusions of endotoxin (5 micrograms/kg total dose), then monitored for up to 5 h. Postmortem extravascular lung water (EVLW) was significantly higher in the M + E group (14.2 +/- 4.4 ml/kg) and the E group (11.9 +/- 3.9 ml/kg) when compared with a normal control (6.6 +/- 1.3 ml/kg) group that did not receive endotoxin. EVLW in a group made neutropenic with nitrogen mustard (6.7 +/- 1.3 ml/kg) and the H + E (7.9 +/- 1.5 ml/kg) groups were not statistically different from each other or from normal controls. Circulating neutrophil counts averaged 32 +/- 42 cells/microliter in the M + E group and 180 +/- 210 cells/microliter in the H + E group. Only minimal histological changes were seen in the H + E group, but the E and M + E lungs had severe pulmonary edema. We conclude that neutrophils are not required for increased EVLW and decreased arterial O2 partial pressure after endotoxin infusion, and hydroxyurea prevents at least part of the pulmonary edema after endotoxin by a mechanism that is not neutrophil dependent.     

Effects of crystalloid and colloid fluids on extravascular lung water in hypoproteinemic dogs

We compared the effect of crystalloid to colloid fluid infusion on extravascular lung water (EVLW) in hypoproteinemic dogs. Plasmapheresis was used to decrease plasma colloid osmotic pressure (COP) to less than 40% of its base-line level. Five animals were then infused with 0.9% sodium chloride (saline), five with 5% human serum albumin (albumin), and five with 6% hydroxyethyl starch (hetastarch) to increase the pulmonary arterial occlusive pressure by 10 Torr in comparison to the postplasmapheresis level for a 5-h study interval. On completion of the procedure, the lungs were harvested and EVLW measured by the blood-free gravimetric technique. Three to six times the volume of saline compared with albumin or hetastarch (P less than 0.001) was infused. In the saline animals, COP was decreased to 3.3 +/- 1.3 Torr, whereas COP was increased to 18.1 +/- 1.4 Torr in albumin animals (P less than 0.001) and 20.1 +/- 1.6 Torr in the hetastarch group (P less than 0.001). The saline-treated dogs developed gross signs of systemic edema. The EVLW was 8.1 +/- 0.9 ml/kg in saline animals compared with 5.3 +/- 2.1 ml/kg in the albumin (P less than 0.05) and 4.1 +/- 1.4 ml/kg in the hetastarch (P less than 0.01) groups. These data indicate that crystalloid fluid infusion during hypoproteinemia is associated with the development of both systemic and pulmonary edema.     

Regional measurement of canine skeletal muscle blood flow by positron emission tomography with H2(15)O.

Positron emission tomography (PET) with H2(15)O was used as an in vivo, relatively noninvasive, quantitative method for measuring regional blood flow to hindlimb skeletal muscle of anesthetized dogs. A hydrooccluder positioned on the femoral artery was used to reduce flow, and high-flow states were produced by local infusion of adenosine. Three to four measurements were made in each animal. Approximately 40 mCi of H2(15)O were injected intravenously, and serial images and arterial blood samples were acquired over 2.5 min. Data analysis was performed by fitting tissue and arterial blood time-activity curves to a modified, single-compartment Kety model. The model equation was also solved on a pixel-by-pixel basis to yield maps of regional skeletal muscle blood flow. After each PET determination, flow was measured with radioactive microspheres. Results of the PET measurements demonstrated that basal flow to hindlimb skeletal muscle was 3.83 +/- 0.36 ml x min(-1) x 100 g(-1) (mean +/- SE). This value was in excellent agreement with the microsphere data, 3.73 +/- 0.32 ml x min(-1) x 100 g(-1) (P = 0.69, not significant). Adenosine infusion resulted in flows as high as 30 ml x min(-1) x 100 g(-1), and the PET and microsphere data were highly correlated over the entire range of flows (r2 = 0.98, P < 0.0001). We conclude that muscle blood flow can be accurately measured in vivo by PET with H2(15)O and that this approach offers promise for application in human studies of muscle metabolism under varying pathophysiological states.     

Changes in transthoracic electrical impedance during endotoxemia in dogs.

Our aim was to investigate the role of hematocrit (H) and respiration in transthoracic electrical impedance during endotoxemia. Transthoracic electrical impedance at end-expiratory apnea (Z0) and at end-inspiration (Zmax), H values, and extravascular lung water level (EVLW), estimated by means of gravimetric analysis and the impedance method, were measured in splenectomized and mechanically ventilated dogs. In endotoxemia, there were increases in Z0, Zmax, H and the respiratory frequency. In the splenectomized dogs, both impedances slightly increased without any significant change in H. In the ventilated dogs, Z0, and Zmax increased similarly, while H increased. In the splenectomized, ventilated dogs, no changes were found in the impedances or H. The EVLW values showed that there was no serious edema in the endotoxemic groups. The results suggest that Z0 increased mainly in association with the increase in H. We conclude that the noninvasive measurements of the changes in impedance can be used for continuous monitoring of the fluid and gas shifts in the thorax.     

Pulmonary edema with smoke inhalation, undetected by indicator-dilution technique

Despite experimental evidence for an increase in extravascular lung water (EVLW) after inhalation injury, thermal-dye estimations of EVLW, extravascular thermal volume (EVTV), have repeatedly failed to demonstrate its presence in patients. This situation was evaluated in a sheep model. Under halothane anesthesia one lung was insufflated with cotton smoke and the other with air. EVTV values were 8.4 +/- 0.48 ml/kg at base line and were not elevated at 24 h after smoke inhalation (8.3 +/- 0.45 ml/kg; means +/- SE). Gravimetric analysis 24 h after smoke inhalation showed the development of edema in smoke-exposed lungs. The blood-free wet weight-to-dry weight ratio of the smoke-exposed lungs (5.4 +/- 0.32) was significantly higher compared with the contralateral unsmoked lungs (4.3 +/- 0.15; P less than or equal to 0.05). The thermal-dye technique thus underestimates EVLW. Poor perfusion of the smoke-exposed lungs 24 h after injury was demonstrated indirectly by killing a group of sheep with T-61, an agent that causes a dark red coloration of well-perfused lung areas, as well as directly by measurement of blood flow utilizing a radiolabeled microsphere technique. Thus the inability of the thermal-dye technique to detect the lung edema may be the result of poor perfusion of the injured lung.     

Lung expansion and the perialveolar interstitial pressure gradient

We have determined the combined effects of lung expansion and increased extravascular lung water (EVLW) on the perialveolar interstitial pressure gradient. In the isolated perfused lobe of dog lung, we measured interstitial pressures by micropuncture at alveolar junctions (Pjct) and in adventitia of 30- to 50-microns microvessels (Padv) with stopped blood flow at vascular pressure of 3-5 cmH2O. We induced edema by raising vascular pressures. In nonedematous lobes (n = 6, EVLW = 3.1 +/- 0.3 g/g dry wt) at alveolar pressure of 7 cmH2O, Pjct averaged 0.5 +/- 0.8 (SD) cmH2O and the Pjct-Padv gradient averaged 0.9 +/- 0.5 cmH2O. After increase of alveolar pressure to 23 cmH2O the gradient was abolished in nonedematous lobes, did not change in moderately edematous lobes (n = 9, EVLW = 4.9 +/- 0.6 g/g dry wt), and increased in severely edematous lobes (n = 6, EVLW = 7.6 +/- 1.4 g/g dry wt). Perialveolar interstitial compliance decreased with increase of alveolar pressure. We conclude that increase of lung volume may reduce perialveolar interstitial liquid clearance by abolishing the Pjct-Padv gradient in nonedematous lungs and by compressing interstitial liquid channels in edematous lungs.     

Intrapulmonary oxygen consumption in experimental pneumococcal pneumonia

To test the hypothesis that lung affected by acute bacterial pneumonia consumes significant amounts of O2, whole-body O2 consumption (VO2) was measured simultaneously by collection of expired gas (VO2exp) and by the Fick principle (VO2Fick) in five dogs with acute experimental pneumococcal pneumonia and in five uninfected controls. This approach is based on the premise that VO2Fick will not detect lung VO2, whereas the expired gas measurement represents the true whole-body VO2, including the lung. In controls VO2 exp averaged 110 +/- 20 ml/min (4.78 +/- 0.78 ml.min-1.kg-1), and VO2Fick was nearly identical at 114 +/- 21 ml/min (4.96 +/- 0.79 ml.min-1.kg-1). The VO2Fick in the pneumonia group was 127 ml/min, similar to both control group values when indexed for body weight (4.91 +/- 1.17 ml.min-1.kg-1). VO2exp, however, was 146 +/- 46 ml/min (5.74 +/- 1.57 ml.min-1.kg-1), exceeding VO2Fick by an average of 20 +/- 9 ml/min (P less than 0.01). This between-method difference of 20 +/- 9 ml/min (or 24 ml/min if the difference in the control group is assumed to apply to the pneumonia group) amounted to 13-15% of whole-body VO2 and can be attributed to VO2 in the lung, presumably by cells involved in the acute inflammatory response. Implications include the potential for significant underestimate of whole-body VO2 by the Fick method when used in the presence of lung inflammation and overestimate of blood flow to shunting or low ventilation-perfusion ratio lung units by the O2 method of measuring venous admixture-like perfusion. This observation may also explain the disproportionate hypoxemia sometimes seen in patients with severe pneumonia.     

Regional lung hematocrit in humans using positron emission tomography

Regional lung hematocrit ratio (R) was measured in five normal subjects and five patients (2 with pneumonia, 2 with nephrotic syndrome with anemia, and 1 with pancreatitis) using positron emission tomography, a red cell marker 11CO, and a plasma marker [methyl-11C]albumin). The measurements were made in a transaxial thoracic section at midheart level with the subject in supine posture and with a spatial resolution of 1.7 cm. The normal regional hematocrit ratio (means +/- SE) calculated for the lung was 0.90 +/- 0.014, 0.94 +/- 0.023 for the thoracic wall, and 1.00 +/- 0.003 for the heart chambers. The regional lung hematocrit ratio in the patients ranged between 0.81 and 0.86. No correlation was found among the regional lung hematocrit ratio and regional blood volume, lung extravascular density, and the peripheral hematocrit (obtained from venous blood samples). To the extent that 70% of the pulmonary blood in the field of view is in larger vessels with normal hematocrit, the hematocrit in the capillary bed is approximately two-thirds that of the peripheral venous value. Blood volume measurements on the basis of single vascular tracers need to take account of these results.     

Amiloride impairs lung water clearance in newborn guinea pigs

To determine whether epithelial ion transport is physiologically important for lung water clearance after birth, the sodium transport inhibitor amiloride or its vehicle saline was given intratracheally to newborn full-term guinea pigs before the first breath. Guinea pigs given saline intratracheally breathed normally and had arterial O2 saturations (SaO2) greater than 94%. In contrast, guinea pigs that had an estimated 10(-4) M intra-alveolar concentration of amiloride had chest wall retractions and 88 +/- 3.6% (SD) SaO2 (P less than 0.01). Extravascular lung water (EVLW) per gram of dry lung weight 4 h after birth was significantly greater in newborns that received amiloride (8.3 +/- 1.1, n = 5) than in those that received saline (5.6 +/- 0.9, n = 7, P less than 0.01). The degree of perivascular fluid cuffing at 25 cmH2O inflation was quantitatively similar in amiloride- and saline-treated animals. The effect of amiloride was dose dependent. Intratracheal amiloride did not affect EVLW in 9-day-old guinea pigs. This study demonstrates that intratracheal amiloride before the first breath results in respiratory distress, hypoxemia, and an abnormally high EVLW. Epithelial sodium transport contributes normal lung liquid clearance after birth.     

Pulmonary blood flow distribution after lobar oleic acid injury: a PET study

We evaluated the importance of hypoxic vasoconstriction as a mechanism for pulmonary blood flow reduction during unilobar oleic acid lung injury in dogs. Pulmonary blood flow (PBF) and lung water were measured with positron emission tomography. Data from the injured left (LCL) and right (RCL) caudal lobes were compared in 23 dogs. Six dogs were used to demonstrate that endotoxin (15 micrograms/kg) prevents changes in regional PBF during selective hypoxic ventilation of the LCL. In 17 dogs, oleic acid (OA, 0.015 ml/kg) was injected into the LCL through a balloon-wedged pulmonary arterial catheter. Five dogs received OA only (control group), eight received endotoxin (15 mcg/kg) before OA was administered (endotoxin group), and four were treated with prostaglandin E1 (PGE1) after OA (PGE1 group). The base-line left-to-right PBF ratio (LCL/RCL PBF) was 1.01 +/- 0.11 (SD) for the control group and 1.07 +/- 0.16 for the PGE1 group. One minute after OA, LCL/RCL PBF feel significantly (0.32 +/- 0.15 and 0.32 +/- 0.13 for the control and PGE1 groups, respectively) before any significant increase in lung water was detected. In all 17 dogs that received OA, the LCL/RCL PBF remained severely reduced 60 min after OA compared with base-line values (0.41 +/- 0.15, 0.49 +/- 0.06, and 0.26 +/- 0.13 for the control, PGF1, and endotoxin groups, respectively) despite treatment with endotoxin or PGE1. Lung water measurements obtained 60 min after OA increased significantly (P less than 0.05) in the injured lobe (LCL) but not in the normal lobe (RCL) in all dog groups, whereas PBF to the LCL remained significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiopulmonary adaptations to pneumonectomy in dogs. I. Maximal exercise performance.

Maximal exercise performance was evaluated in four adult foxhounds after right pneumonectomy (removal of 58% of lung) and compared with that in seven sham-operated control dogs 6 mo after surgery. Maximal O2 uptake (ml O2.min-1.kg-1) was 142.9 +/- 1.9 in the sham group and 123.0 +/- 3.8 in the pneumonectomy group, a reduction of 14% (P less than 0.001). Maximal stroke volume (ml/kg) was 2.59 +/- 0.10 in the sham group and 1.99 +/- 0.05 in the pneumonectomy group, a reduction of 23% (P less than 0.005). Lung diffusing capacity (DL(CO)) (ml.min-1.Torr-1.kg-1) reached 2.27 +/- 0.08 in the combined lungs of the sham group and 1.67 +/- 0.07 in the remaining lung of the pneumonectomy group (P less than 0.001). In the pneumonectomy group, DL(CO) of the left lung was 76% greater than that in the left lung of controls. Blood lactate concentration and hematocrit were significantly higher at exercise in the pneumonectomy group. We conclude that, in dogs after resection of 58% of lung, O2 uptake, cardiac output, stroke volume, and DL(CO) at maximal exercise were restricted. However, the magnitude of overall impairment was surprisingly small, indicating a remarkable ability to compensate for the loss of one lung. This compensation was achieved through the recruitment of reserves in DL(CO) in the remaining lung, the development of exercise-induced polycythemia, and the maintenance of a relatively large stroke volume in the face of an increased pulmonary vascular resistance.     

Distribution of extravascular lung water after acute smoke inhalation

Anesthetized dogs with thoracotomy were injected with Evans blue dye and were exposed acutely (5 min) to wood smoke inhalation. Thin slices from freeze-dried samples were photographed and assessed for periarterial and perivenous cuff area and for blue coloration with a score of 0 to 5. Bloodless extravascular lung water (EVLW) was also measured. The smoke-exposed animals were compared with controls and with animals exposed to alloxan or to high-pressure-induced pulmonary edema. EVLW at 2 h after smoke (6.46 +/- 0.80) was above control value (4.30 +/- 0.63) but not different from the alloxan (6.13 +/- 0.70) or high-pressure (6.88 +/- 1.30) groups. Despite the similarity in EVLW in the edematous lungs, there were marked differences in the intensity of blue color and size of cuffing around arteries and veins: the smoke, alloxan, and high-pressure groups had blue color scores of 1.0 +/- 0.1, 2.9 +/- 0.3, and 0.3 +/- 0.1, respectively. These scores indicated a large increase in microvascular permeability to proteins in the alloxan group, a moderate increase in the smoke group, and minimal change in the high-pressure group. The perivascular cuff area was largest in the alloxan group and moderate in the smoke and high-pressure groups. The cuff area was higher for arteries than for veins in all groups except the 0.5-h smoke group. We conclude that smoke inhalation causes a moderate increase in permeability and EVLW compared with alloxan. The extravascular lung water accumulates preferentially around the arteries, but the size of the perivascular cuff is not similar for all causes of pulmonary edema.     

Quantitative measurement of regional pulmonary blood flow with positron emission tomography

We have measured regional pulmonary blood flow (PBF) in normal dogs with positron emission tomography (PET) and 15O-labeled water (H2(15)O). The method is nondestructive, quantitative, and repeatable. To measure PBF, PET is used to measure both the initial and equilibrium distribution of lung activity after H2(15)O infusion. The data are then interpreted with a one-compartment mathematical model. Measurements of PBF in dogs with H2(15)O (PBF-water) were compared with PBF measured with 68Ga microspheres (PBF-MS), and a close correlation was observed: PBF-water = 0.82 PBF-MS + 25.4 (R = 0.97, n = 52). In another set of animals an important assumption of the method, namely that the tracer is fully extracted during a single pass through the lung, was demonstrated using a single-probe residue-detection technique. Computer simulations were performed to illustrate the sensitivity of the method to errors in the measured variables of tracer activity or tissue-blood partition coefficient. Results showed only small error magnification for the range of values observed in these studies.     

Neurogenic pulmonary edema in a pulmonary normotensive model

In the present study our aim was to determine whether or not neurogenic pulmonary edema would develop from a brief pulse of intracranial pressure (ICP) in the absence of any obvious pulmonary hypertension. There were three groups of cats: sham-operated controls, ICP only, and ICP plus variable occlusion of the pulmonary artery. Partial occlusion of the pulmonary artery was carried out by placing a ligature around the pulmonary trunk and mechanically constricting the artery to maintain pulmonary arterial pressure (PAP) and left atrial pressure (LAP) at pre-ICP levels. In sham-operated animals the extravascular lung water/blood free dry weight ratio (EVLW/BFDW) was 3.26 +/- 0.07 and broncho-alveolar lavage (BAL) protein, 6.49 +/- 0.62 mg/g lung. ICP-only caused a rise in PAP, left atrial pressure, and EVLW/BFDW to 3.67 +/- 0.08 (P less than 0.05). ICP with partial occlusion of the pulmonary artery prevented any rise in PAP or LAP while EVLW/BFDW rose to 3.67 +/- 0.10 (P less than 0.05) and BAL protein was 8.37 +/- 1.27 mg/g lung. Our results show that EVLW/BFDW can increase with neurogenic pulmonary edema in cats in the absence of an obvious increase in pulmonary arterial or left atrial pressure.     

Effect of superior vena caval hypertension on alloxan-induced lung injury in dogs

To investigate how fast and to what extent superior vena caval hypertension (SVCH) increases lung water in acute increased-permeability state, we studied the time course of lung water accumulation for 3 h in anesthetized dogs under different treatments: 1) controls without intervention (5 dogs), 2) SVCH alone (5 dogs), 3) mild lung microvascular injury induced by low-dose alloxan (75 mg/kg) alone (5 dogs), and 4) SVCH coupled with low-dose alloxan (5 dogs). Neither low-dose alloxan alone nor SVCH alone [superior vena caval pressure (Psvc) = 11.0 +/- 3.1 (SD) mmHg] increased lung water significantly. The SVCH coupled with low-dose alloxan (Psvc = 11.3 +/- 2.7 mmHg) doubled extravascular lung thermal volume measured by the thermal-dye dilution technique within 1 h (5.3 +/- 0.9 ml/kg at base line and 10.9 +/- 4.7 ml/kg at 1 h), then remained unchanged (12.5 +/- 5.7 ml/kg at 3 h). This increase in lung water was confirmed by gravimetric method (5.69 +/- 1.71 g/g blood-free dry wt). We conclude that SVCH is one of the factors that may promote lung water accumulation in increased-permeability state.     

Effect of prolonged renal dysfunction on intravascular and extravascular pulmonary fluid volumes during left atrial hypertension

To examine the development of pulmonary edema during experimental renal dysfunction, left atrial pressure was altered in 14 mongrel dogs divided into two groups. Group 1 was composed of seven control animals, and Group 2 was composed of seven animals with surgically induced renal failure (1 week of bilateral ureteral ligation). Data were obtained at two levels of matched transmural pulmonary vascular pressure (defined as mean left atrial pressure less serum protein osmotic pressure). In the animals with renal dysfunction, extravascular lung water (EVLW) (thermal-green dye technique) was higher at moderately (-1 to -2 mm Hg) and severely elevated (11 to 12 mm Hg) vascular driving pressures (11.5 +/- 1.2 cc/kg vs 10.6 +/- 0.8 cc/kg and 14.8 +/- 1.3 cc/kg vs 13.0 +/- 1.9 cc/kg, respectively, both P less than 0.05 vs control). Because protein osmotic pressure was lower in the renal failure group (15.0 +/- 1.8 mm Hg vs 18.4 +/- 1.4 mm Hg, P less than 0.05), greater accumulations of extravascular lung water occurred at lower levels of left atrial pressure (14.2 +/- 1.4 mm Hg vs 17.1 +/- 1.2 mm Hg, P less than 0.05; 26.8 +/- 2.6 mm Hg vs 29.5 +/- 2.3 mm Hg, P less than 0.01). In addition, when the ratio of EVLW/PBV (pulmonary blood volume) was examined in both groups at each stage of the experiment, the ratio was greater in the Group 2 animals at each elevated pressure, suggesting increased permeability with renal dysfunction. In conclusion, pulmonary edema formation occurs at lower left atrial pressures in the setting of sustained renal dysfunction, this phenomenon can be partially explained by lower protein osmotic pressure though altered pulmonary microvascular permeability may contribute to edema formation.     

Histamine-induced pulmonary edema distal to pulmonary arterial occlusion

Histological studies provide evidence that the bronchial veins are a site of leakage in histamine-induced pulmonary edema, but the physiological importance of this finding is not known. To determine if a lung perfused by only the bronchial arteries could develop pulmonary edema, we infused histamine for 2 h in anesthetized sheep with no pulmonary arterial blood flow to the right lung. In control sheep the postmortem extravascular lung water volume (EVLW) in both the right (occluded) and left (perfused) lung was 3.7 +/- 0.4 ml X g dry lung wt-1. Following histamine infusion, EVLW increased to 4.4 +/- 0.7 ml X g dry lung wt-1 in the right (occluded) lung (P less than 0.01) and to 5.3 +/- 1.0 ml X g dry wt-1 in the left (perfused) lung (P less than 0.01). Biopsies from the right (occluded) lungs scored for the presence of edema showed a significantly higher score in the lungs that received histamine (P less than 0.02). Some leakage from the pulmonary circulation of the right lung, perfused via anastomoses from the bronchial circulation, cannot be excluded but should be modest considering the low pressures in the pulmonary circulation following occlusion of the right pulmonary artery. These data show that perfusion via the pulmonary arteries is not a requirement for the production of histamine-induced pulmonary edema.     

Lung volume and compliance in neonatal rats

Lung volumes and static lung compliance were measured in decapitated three day-old neonatal Long Evans' rat pups. Compliance was measured in situ (open chest method) using a water manometer and syringe system. Mean total lung capacity at 20 cm H2O pressure (TLC20) was 0.678 ml. Minimum lung volume after experimental inflation was 0.197 +/- 0.048 ml, and vital capacity was 0.56 ml (Vmax20). The mean lung compliance value for the approximate tidal loop (between 3 and 12 cm H2O) equalled 26.2 microliters air/cm H2O for the inflation limb and 23.1 microliters/cm H2O for the deflation limb.