Lung Airspaces Research Articles

Endotoxin-Induced Neutrophilic Alveolitis and Macrophage Chemotaxin Production in Sheep

The mechanism(s) responsible for endotoxin-induced pulmonary leukostasis has not yet been elucidated. We studied ten unanesthetized sheep by performing serial bronchoalveolar lavages (BAL) before and after infusing Escherichia coli endotoxin to determine whether or not neutrophils appeared in the airways and whether or not endotoxemia stimulated alveolar macrophages to produce neutrophil chemotactic activity. The absolute number and percentage of neutrophils recoverable by BAL increased significantly at 24 hours after infusion of endotoxin. Alveolar macrophages isolated from the BAL of sheep after endotoxemia produced a substance that is chemotactic for neutrophils, a response that is also maximal 24 hours after endotoxin infusion. We conclude that endotoxemia causes migration of neutrophils into lung air spaces and that this response may result from in vivo production of a chemotactic factor(s) by activated alveolar macrophages.

Quantity of anti-leucoprotease relative to α1-proteinase inhibitor in peripheral airspaces of the human lung

1. Peripheral airspaces were selectively lavaged using balloon-tipped catheters of 2 mm diameter. 2. Molar anti-leucoprotease/alpha 1-proteinase inhibitor ratios as determined in these lavage fluids by enzyme immunoassays ranged from 0.02 to 0.14 (mean 0.08). 3. These data indicate that peripheral airspaces contain minor amounts of anti-leucoprotease relative to alpha 1-proteinase inhibitor. This observation does not necessarily mean that anti-leucoprotease is of minor importance in protecting the lung interstitium.

Pulmonary epithelial sieving of small solutes in rat lungs.

Transport and consumption of glucose from the air spaces of isolated, fluid-filled lungs can result in significantly lower glucose concentrations in the air spaces than in the perfusate compartment (11). This concentration difference could promote the osmotic movement of water from the air spaces to the perfusate, but the rate of fluid extraction from the air spaces would then be limited by the rates of electrolyte transport through the epithelium. In the present study, measurements were made of solute and water losses from the air spaces of fluid-filled rat lungs and the transport of these solutes and water into the vasculature after addition of hypertonic glucose or sucrose to the perfusate. Increases in the concentrations of Na+, Cl-, K+, and labeled mannitol in the air space were initially comparable to those of albumin labeled with Evans blue. Similarly, decreases in electrolyte concentrations in the perfusate were comparable to those of labeled albumin, indicating that very little solute accompanied the movement of water out of the lungs. Nor was evidence found that exposure of the vasculature to hypertonic glucose resulted in an increase in the rate at which fluid was reabsorbed from the air spaces over a 1-h interval, aside from an initial, abrupt loss of solute-free water from the lungs. These observations suggest that perfusion of fluid-filled lungs with hypertonic solutions of small solutes results in the extraction of water from the air spaces and pulmonary parenchyma across membranes that resist the movement of electrolytes and other lipophobic solutes.

A theoretical analysis of interrupter technique for measuring respiratory mechanics.

The application of the flow interrupter technique to series and parallel models of the respiratory system is examined theoretically, assuming instantaneous transmission of pressures and incompressible gases in the lung air spaces. The initial pressure change observed immediately after occlusion divided by the preocclusion flow gives an initial resistance (Rinit) equal to that of the airway tree when the model consists of compartments connected in parallel. When the compartments are connected in series, Rinit is the resistance of the most proximal airway only. In general, the initial pressure change is followed by a second slower change, reflecting equilibration of pressures between the compartments. The total postocclusion pressure change divided by the flow gives a steady-state resistance (Rss) whose value depends on the ventilation history before occlusion. When this history consists of a relaxed expiration Rss asymptotes from Rinit to a value higher than the zero-frequency resistance of the model as the expiratory time increases. However, the relative contributions of serial and parallel pendelluft and viscoelasticity to Rss cannot be determined from pressure and flow measurements made at the airway opening. Therefore in disease, the interrupter method does not permit one to say whether ventilation inhomogeneity or alteration in lung tissue properties is the predominant abnormality.

Degradation and reutilization of alveolar phosphatidylcholine by rat lungs.

We have shown previously that phospholipids instilled through the trachea are removed from the air spaces in isolated rat lungs by a process that is stimulated by beta-adrenergic agonists. In this study, we evaluated the fate of radiolabeled lipid vesicles [50% [3H]dipalmitoyl phosphatidylcholine (DPPC), 25% phosphatidylcholine (PC), 15% cholesterol, and 10% phosphatidylglycerol (PG)]. Vesicles were instilled through the trachea of anesthetized rats, and the lungs removed for perfusion. The percent of instilled 3H that could not be removed from lungs by extensive lung lavage increased progressively; at 3 h this fraction was 25.8 +/- 0.63% (mean +/- SE; n = 8). The percent of dpm in the lung homogenate accounted for by PC decreased progressively while dpm in lyso-PC, unsaturated PC, and aqueous soluble metabolites [choline, choline phosphate, glycerophosphorycholine, and cytidine 5'-diphosphate (CDP) choline (CDP-choline) increased. The dpm in microsomal and lamellar body fractions isolated from lung homogenates also increased progressively with time of perfusion. The presence of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) significantly stimulated both uptake of DPPC and the appearance of radioactivity in metabolites and subcellular organelles. This effect of 8-BrcAMP was not due to stimulation of phospholipase A activity. These results indicate that exogenous phospholipids instilled into the air spaces of rat lungs are internalized and degraded by a process that is stimulated by cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of aerosols to measure in vivo volume-dependent changes in lung air space dimensions.

Using measurements of aerosol recovery following a 5-s breath hold [NRC(5)] as indices of lung air space dimensions, we evaluated the in vivo changes in these dimensions associated with changes in lung volume (VL). In anesthetized dogs, single breaths of a 1.2-micron monodisperse aerosol were introduced into the respirator's cycle at a number of isovolume points on the inflation and deflation limb of the pressure-volume curve for the dog's lungs. At isovolume, NRC(5) measured off the inflation limb was slightly larger than NRC(5) measured off the deflation limb, implying a larger mean air space dimension for the air space configuration on the inflation vs. the deflation limb. Since a constant aerosol tidal volume (VT) was used for all VL in all dogs, the proportion of the lung filled with aerosol, VT/VL = Pn (where Pn is defined as an index of aerosol penetration into the lung periphery), varied along with VL. In all dogs, we found that, for NRC(5) measurements with Pn less than 0.33, NRC(5) steadily increased with increasing VL, which implies an increasing mean air space dimension as VL increases. However, when we account for the effect that changes in Pn with increasing VL have on NRC(5), we conclude that the observed increase in NRC(5) with VL is primarily due to decreases in Pn and not increases in the mean air space dimension as VL increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Localized pulmonary neutrophil influx induced by lung lavage in sheep.

The kinetics and distribution of neutrophil (PMN) influx into lung air spaces subsequent to bronchoalveolar lavage (BAL) were studied in adult sheep. The concentration of PMNs in BAL fluid peaked at 6 h and remained elevated for 48 h after the initial lavage. The response was observed primarily in the lung segment originally lavaged although minor changes were seen in BAL from immediately adjacent regions. No response was observed in the contralateral lung. Except for a transient decrease in pulmonary alveolar macrophages and monocytes at 6 h, changes in mononuclear cell populations (pulmonary alveolar macrophages, monocytes and lymphocytes) were minimal.

A mathematical model of particle retention in the air-spaces of human lungs.

Knowledge of the total and regional lung retention of particles inhaled continuously by man over long periods can be useful in understanding the potential role of inhaled particles in the pathogenesis of lung diseases. Owing to practical and ethical considerations, however, little or no experimental information exists. A mathematical model of particle retention simulating environmental and occupational exposures has therefore been developed that takes into account particle deposition, tracheobronchial clearance, and two phases of alveolar clearance in the Weibel A anatomical lung model. The derived equations of retention kinetics predict retention of particles as a function of exposure time. For a continuous exposure (simulating environmental conditions) to 4 microns particles, the model predicts that retained particles approach an equilibrium between deposited and cleared particles with the 95% level being reached in 293 days. For an intermittent exposure (simulating occupational conditions) equilibrium is approached in five years. The whole lung burden of particles is predicted to be 9% of the total mass that entered the lung after a one-year environmental exposure and 1.5% after a 25-year occupational exposure. The equilibrium surface concentration and integrated dose of particles per airway generation predict enhanced risk to the pathogenic effects of inhaled particles in the large airways and respiratory bronchioles.

Combined epidermoid and adenocarcinoma in diffuse interstitial pulmonary fibrosis

This report documents a case of combined epidermoid and adenocarcinoma with idiopathic diffuse interstitial fibrosis developing in the lung. This type of carcinoma with diffuse interstitial fibrosis occurs only rarely in the lungs, in contrast to such carcinoma without fibrosis, which occurs less rarely. A 79-year-old man died of respiratory insufficiency three years after the was diagnosed as having diffuse interstitial pulmonary fibrosis. Six months prior to his death. a tumor shadow was noticed on a radiograph of his chest. Postmortem examination revealed diffuse interstitial pulmonary fibrosis and a primary lung tumor situated peripherally in the right lower lobe. The histologic features of the tumor closely resembled those of mucoepidermoid carcinoma of the major bronchi. However, the tumor had no relation to any bronchi or bronchial glands, and it was evident that no relation to any bronchi or bronchial glands, and it was evident that it had originated from the surface epithelium of the abnormally altered distal airspaces of the honeycomb lung. It is suggested that the malignantly transformed cells originally possessed the potential for bidirectional differentiation to epidermoid and mucous cells.

Organ-Selective Action of an Antitumor Drug: Pharmacologic Studies of Liposome-Encapsulated β-Cytosine Arabinoside Administered via the Respiratory System of the Rat2

beta-Cytosine arabinoside (Ara-C) in free and liposome encapsulated form was administered to Wistar rats by intratracheal institution. Free [3H]Ara-C administered in this manner rapidly left the lung and entered the systemic circulation. Liposome-encapsulated [3H]Ara-C persisted in the lung for a long period, with little redistribution to other tissues. Liposomes administered via the trachea became widely distributed throughout the lung air spaces, as evidenced by the histochemical localization of liposomes containing horse-radish peroxidase. Free Ara-C (5 mg/kg) administered into the trachea effectively suppressed macromolecular incorporation of [14C]thymidine ([14C]dThd) in the bone marrow and gut as well as in the lung. Liposome-encapsulated Ara-C (5 mg/kg) effectively suppressed macromolecular incorporation of [14C]dThd in the lung but had little effect on this process in the gut and bone marrow. Our results suggest that liposome-encapsulated Ara-C may be able to produce a local pharmacologic effect within the lung without producing adverse side effects in other tissues. This observation may be relevant to the chemotherapy of pulmonary metastases.

A new noninvasive method for the simultaneous determination of cardiac output, VA/QC disparity, and the magnitude of peripheral perfusion, suitable for use in the critically ill patient.

A noninvasive technique for determining cardiac output, lung blood-tissue volume, and the volume of perfused body tissue in shock states has been developed from analysis of the pulmonary washout of several physiologically inert tracer gases. Canine preparations and a computer-based simulation were used to evaluate the accuracy and feasibility of the technique. The dogs were ventilated with 10% helium, 10% N2O, 0.45% C2H2, 39.5% N2, and 40% O2 mixture, and washed out with 60% N2 and 40% O2. End-tidal volume excretion differences between the three inert gases helium, N2O, and C2H2 resulted from differences in the blood/gas partition constants (lambda) of the test gases. Helium, which has a very low lambda, is contained in lung air space, whereas N2O and C2H2, with moderate lambda's, are distributed to lung air space, blood, and perfused tissues. Computer modeling of the cardiopulmonary and body perfusion gas transport permitted calculation of alveolar ventilation, VA/VA disparity, pulmonary blood-tissue volume, pulmonary blood flow, VAQć, and perfused body volume in the canine experiments. In experimental shock settings and in a variety of control situations over an eightfold range of flows the pulmonary blood flow calculated from the N2O and C2H2 washout was generally within +/- 15% of the cardiac output determined by the cardiogreen technique.

Role of autonomic nervous system controlling surface tension in fetal rabbit lungs.

After the maternal abdomen was opened under methoxyflurane anesthesia, fetal rabbits of 27.5 days gestation were given injections through the intact uterine wall of saline, pilocarpine, isoxsuprine, muscarine, phenylephrine, atropine, phenoxybenzamine, or propranolo, alone or in appropriate combinations. Fetal rabbits were delivered by hysterotomy and killed without breathing 2.5 h later. Static pressure-volume curves with air showed improved retention on deflation in fetal rabbits that had injections of pilocarpine, or isoxsuprine, but not of muscarine or phenylephrine. The effect of pilocarpine on the pressure-volume curve was blocked by atropine, phenoxybenzamine, and propranolol, and the effect of isoxsuprine was blocked by propranolol but not phenoxybenzamine. The data suggest that pilocarpine produces secretion of surfactant into lung air spaces by exciting the sympathetic nervous system, a known function of pilocarpine, rather than the parasympathetic nervous system. This may result in stimulation of the same beta-adrenergic receptors affected by isoxsuprine which is also thought to stimulate surfactant secretion.

Lung surface tension and air space dimensions from multiple pressure-volume curves.

Pressure-volume (PV) curves of excised cat, dog, rabbit, and rat lungs were determined in a sequence of three conditions: 1) normal-surface, air-filled; 2) saline-filled; and 3) polyoxyethylene (20) sorbitan monolaurate-(Tween 20) surface, air-filled. Since the surface tension of lung washings containing 2% Tween 20 is constant, the Tween-surface air-filled lungs presumably exhibit the pressure-volume behavior of lungs with constant surface tension. These data along with the assumption of equivalent geometry in the three conditions permit calculation of the variation of surface tension in the normal lung as a function of volume without assuming a specific surface area vs. volume function or a maximum surface tension. The calculated surface tension dropped during deflation from a high of 50 dyn/cm total lung capacity (TLC) to a low of 4 dyn/cm (less than 25% TLC) with the species being roughly similar. The PV behavior of Tween-surface lungs appears to fit a simple model of alveolar expansion. Air dimensions calculated for the four species on the basis of this model are ordered in the same sequence as morphological measurements, but larger in magnitude.

Solute permeability of the alveolar epithelium in acute hemodynamic pulmonary edema in dogs.

Ten anesthetized dogs, 48 h postintravenous 131I-albumin injection, had a segment of lung airspace isolated by a balloon-tipped catheter lodged in a bronchus. An isotonic saline solution containing trace amounts of Blue Dextran, 125I-albumin, and 57Co-cyanocobalamin was instilled into the lung segment. During control periods, lung saline was absorbed at a rate of 0.133% per minute as measured by indicator dilution of Blue Dextran. Only 57Co-cyanocobalamin crossed the epithelium. Acute hemodynamic pulmonary edema was produced by aortic constriction plus saline overload. In pulmonary edema the fluid volume in the airspace increased at the rate of 0.96% per minute, and there was a significant influx of 131I-albumin into the lung saline from the blood in all animals. However, neither 125I-albumin nor Blue Dextran diffused from the airspace into blood during edema; both were merely diluted by fluid influx. The rate of diffusion of 57Co-cyanocobalamin increased fivefold during edema. A small number of discrete breaks in the lung epithelium allowing bulk flow of interstitial fluid is proposed to account for the one-way movement of albumin in hemodynamic alveolar edema.

Variability in the size of airspaces in normal human lungs as estimated by aerosols.

Measurement of persistence, expressed as half-life (t1/2), of a monodisperse aerosol during breath holding was interpreted as an indirect estimate of the size of intrapulmonary airspaces in healthy subjects. Within subject variation of t1/2 measured over a period of nearly two years was small (coefficient of variation 7-7 to 11-5%). Mean effective airspace diameters were calculated from the aerosol t1/2 values using the settling term from the equation of Landahl (1950). Calculated mean airspace diameters ranged from 0-30 to 0-79 mm for 36 males and from 0-40 to 0-62 mm for 12 females. Airspace diameters correlated poorly with age, height, weight, and lung volumes. These results suggest marked differences in airways geometry in subjects with similar heights and lung volumes.

Immunology of the lower respiratory tract. Functional properties of bronchoalveolar lymphocytes obtained from the normal canine lung.

While the alveolar macrophage has been studied extensively, little attention has been directed toward the immune functions of the bronchoalveolar lymphocyte. These cells, obtained by bronchopulmonary lavage of the normal canine lung, are derived from the air side of the alveolar-capillary membrane of the lower respiratory tract. The distribution of lymphocyte types within the bronchoalveolar cell population was determined and compared with that of leukocytes from blood and spleen.IgG synthesis in vitro was used as a measure of bone marrow-derived lymphocyte (B cell) function, and the blastogenic response of cell cultures to phytohemagglutinin was used as a measure of the presence or absence of thymus-dependent lymphocytes (T cells). De novo synthesis of IgG by bronchoalveolar cells was demonstrated consistently by two independent radio-immunoassays. Therefore, B cells are present in the air spaces of normal canine lungs. T cells were generally not detectable in aliquots of the same cell populations but could be recruited into alveolar spaces after local irritation. The distribution of lymphocyte types within the bronchoalveolar cell population is unique and distinctly different from that of blood and spleen. The spleen is rich in both T cells and B cells, blood is rich in T cells but poor in B cells, whereas the lung lacks T cells and contains substantial numbers of immunoglobulin-producing B cells. The findings indicate that bronchoalveolar lymphocytes do not reflect simply the lymphoid composition of peripheral blood.

Effect of H2O2 on alveolar epithelial barrier properties.

Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-) and actively transport from apical fluid. (0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical at which Isc (or R) was decreased by 50% at one hour () was about 4 mM. However, basolateral exposure led to for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded for Isc (and R) of about 0.4 mM when was given apically, while for basolateral exposure to did not change in the presence of ATAZ. The rate of consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral may affect directly membrane component (e.g., -ATPase) located on the basolateral cell surface. Apical , on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by being relatively sensitive to basolateral (and insensitive to apical) .

Some Aspects of Chronic Respiratory Diseases in Coalminers in New South Wales, Australia

Pneumoconiosis of coalminers appears to be a conglomerate of fibrosis, emphysema, bronchial obstruction and simple clogging of the lung tissues and air spaces with dust. The prevalence of pneumoconiosis and of chronic obstructive bronchitis and emphysema amongst New South Wales coalminers is considered. Schemes for diagnosis and assessment of severity are presented, along with some results of therapy and of post mortem studies. Field tests of lung function are evaluated in comparison with more complex laboratory investigations.

MOISTURE IN THE AIR SPACES OF THE LUNGS AND OXYGEN THERAPY

While on duty at a casualty clearing station in Planders in the summer of 1917, I observed several respiratory phenomena associated with foam in the air passages which conferred an entirely new significance on the presence of moisture in the bronchial tree. The patients who exhibited these symptoms were men who inhaled phosgen and chlorin. These patients had, essentially, a large amount of plasma poured into the air spaces of the lungs, which was not secondary to incompetence of the left ventricle. It was a severe primary edema of the lungs unassociated with myocardial incompetence. One of the things that impressed me was the disproportion between cyanosis and air hunger. The evidence of cyanosis was very much more pronounced than was air hunger in most of the patients. Another very striking experience was the manner in which patients were relieved of cyanosis by the inhalation of oxygen, and the fact