Alveolocapillary Membrane Research Articles

Fluorescein-labeled dextran concentration is increased in BAL fluid after ANTU-induced edema in rats.

Several methodologies have been developed to assess alveolocapillary membrane permeability in acute lung injury. The purpose of this study was to determine the reliability of FITC-dextran compared with radioactive tracers to assess lung permeability alterations. After intraperitoneal administration of alpha-naphthylthiourea (ANTU, 50 mg/kg) or DMSO-ANTU vehicle, the animals were euthanized and their lungs were studied in an isolated-lung preparation. FITC-dextran or radiolabeled tracers were added to the perfusate. At 2 h the bronchoalveolar lavage (BAL) fluid from the ANTU group showed a significantly greater amount of fluorescence in the supernatant after centrifugation of BAL fluid compared with the DMSO group. Consistent results were observed with the radioactive tracers: there was an increase in extravascular albumin space and extravascular lung water compared with the control group. No cleavage of the FITC from the dextran molecule was evident by chromatography comparing samples recovered from the BAL fluid to the pure FITC-dextran molecule. In conclusion, measurement of FITC-dextran in the supernatant of BAL fluid after intravascular administration is a reliable method of assessing lung permeability changes in vivo and ex vivo.

Effects of Hyperthermic Isolated Limb Perfusion with Tumor Necrosis Factor-?? and Melphalan on Pulmonary Function Assessments

High doses of tumor necrosis factor-alpha (TNF) seem to be effective in the treatment of solid tumors in the extremities. By applying current intensive care technology, systemic administration of high doses of TNF levels might be feasible for the treatment of cancer in other localizations. To establish the early and late effects of high systemic TNF levels on the lungs, we determined lung function parameters in 12 patients before and after hyperthermic isolated limb perfusion (HILP) with TNF and melphalan. Because of leakage during perfusion, mean maximum systemic TNF levels of 60.0 ng/ml (range, 0.3-356 ng/ml) were obtained. Significant alterations in the vital capacity (VC), the capillary blood volume (Vc), the diffusing capacity of the alveolocapillary membrane (Dm), and the transfer capacity of the lungs for carbon monoxide per unit alveolar volume (KCO) were observed 1 week after HILP. Eight weeks after HILP, they returned to pretreatment value. Alterations in lung functions were not related to the maximum systemic TNF level. In conclusion, disturbances in pulmonary functions are observed in patients after HILP with TNF and melphalan. These disturbances, which are probably partly caused by high systemic TNF levels, are reversible and would not preclude administration of systemic TNF in high doses.

Lungs in thalassaemia major patients receiving regular transfusion.

Progressive tissue iron deposition from multiple blood transfusions is common in beta-thalassaemia and pulmonary iron deposition may result in parenchymal damage. The objectives of this study were to: 1) determine the predominant pulmonary dysfunction in patients with thalassaemia major; and 2) demonstrate that parenchymal disease, if present, is at the level of the alveolocapillary membrane. Fourteen thalassaemia major patients (13 nonsmokers) receiving regular blood transfusion and without any history of chronic respiratory disease were recruited. Pulmonary function tests and echocardiography were performed before the scheduled transfusions. Three patients with the most restricted lung function were selected for high resolution computerized tomography (CT) of the lungs. One patient had an obstructive pattern with a forced expiratory volume in one second as percentage of forced vital capacity (FEV1/FVC) of 71%. Four patients demonstrated a restrictive pattern, as defined by total lung capacity (TLC) less than 80% predicted with normal FEV1/FVC%. Twelve patients had pulmonary transfer factors for carbon monoxide (TL,CO) below 80% pred, even after correction for the anaemia, indicating parenchymal disease. Eight of these 12 patients had alveolocapillary membrane defect, as demonstrated by a gas transfer factor of the pulmonary membrane (Tm) less than 80% pred. Mean resting arterial oxygen saturation was 95 +/- 2 (range 92-98) %. Eleven patients had oxygen desaturation of 5% or more during exercise on a bicycle ergometer, consistent with interstitial lung disease. There was no clinical or echocardiographic evidence of heart failure. Percentage predicted TLC was inversely correlated with age (r = -0.547; p = 0.043). Both percentage predicted TLC and TL,CO were not correlated with iron burden or desferoxamine ratio. High resolution CT in the three selected patients showed no evidence of pulmonary fibrosis. We conclude that thalassaemia major patients have a predominant restrictive lung dysfunction with pulmonary parenchymal disease and alveolocapillary membrane block. The restrictive and interstitial lung disease could not be accounted for by iron loading or pulmonary fibrosis in our patients.

Evaluation of lung function after intratracheal perfluorocarbon administration in healthy animals.

To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals. Prospective, randomized, controlled study. Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam. Ten adult male New Zealand rabbits. Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters. Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins). These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.

The lung in distress.

The lung functions as a gas exchanger by bringing air and blood into as close proximity as possible. For this purpose, the alveolo-capillary membrane is relatively thin (0.2 µm), making it at the same time very vulnerable for stresses of all kind. Especially in the intensive care unit, the magnitude of the stresses and the cumulative impact of many disorders make the lung accident prone.

Scorpion sting-induced pulmonary oedema: Evidence of increased alveolocapillary membrane permeability

A 16-year-old boy died with acute pulmonary oedema and shock after Tityus serrulatus scorpion sting. The patient showed evidence of cardiac dysfunction and damage, an increase in tracheobronchial aspirate/plasma protein concentration, light microscopic features of the lung compatible with the adult respiratory dystress syndrome and electron microscopic findings compatible with acute lung injury and increased alveolocapillary membrane permeability.

369 Modulation of NAP-2-induced Neutrophil (PMN) Activation by Different Surfactant Preparations

Background: Lung surfactant, a complex composition of phospholipids, neutral lipids and various apoproteins is essential for lung function. In surfactant deficient neonates treatment was done successfully by endotracheal administration of either natural or artificial surfactant preparations. Alteration of the alveolo-capillary membrane may allow blood compounds, such as proteins and cells to interact with surfactant constituents and vice versa.The aim of our study was to investigate surfactant-related effects on PMN since these cells are major effector cells of the primary immune and inflammatory response, involved in pulmonary failure.Methods: PMN, isolated from citrated blood of 3 healthy volunteers were allowed to interact with different surfactant preparations for a time of 30 minutes. Cell activation, reflected by PMN degranulation was detected by measurements of elastase-activity in the supernatant.Results: While NAP-2-induced elastase release was suppressed about by 70% at concentrations of more than 1.0 mg/ml of natural preparations Survanta® and Curosurf®, the only artificial preparation Exosurf® showed slightly stimulating effects. Alveofact®, in contrast seems to combine both, activating and inhibiting properties, interfering with each other. If unstimulated, PMN were not affected by the surfactant preparations.Conclusion: NAP-2-induced activation of isolated PMN is modulated by surfactant. Clinical implications of preparation related effects have to be elucidated.

Pulmonary diffusing capacity after maximal exercise.

To determine the effect of maximal exercise on alveolocapillary membrane diffusing capacity (Dm), 12 professional handball players aged 23.4 +/- 3.3 (SD) yr were studied before and during early recovery from a progressive maximal exercise [immediately (t0), 15 min, and 30 min (t30) after exercise]. Lung capillary blood volume and Dm were determined in a one-step maneuver by simultaneous measurement of CO and NO lung transfer (DLCO and DLNO, respectively) with use of the single-breath breath-hold method. At t0, DLCO was elevated (13.1 +/- 12.0%; P < 0.01) but both DLNO and Dm for CO remained unchanged. Between t0 and t30, both DLCO and DLNO decreased significantly. At t30, DLCO was not different from the control resting value. DLNO (and consequently Dm for CO) was significantly lower than the control value at t30 (-8.9 +/- 8.1%; P < 0.01). Lung capillary blood volume was elevated at t0 (18.0 +/- 19.0%; P < 0.01) but progressively decreased to near control resting values at t30. Differences in the postexercise kinetics of both DLCO and DLNO point to a role of the transient increase in pulmonary vascular recruitment during the recovery period. We concluded that Dm was somewhat decreased in the 30 min after maximal exercise of short duration, but the exact pulmonary mechanisms involved remain to be elucidated.

Pulmonary function in systemic lupus erythematosus is related to distinct clinical, serologic, and nailfold capillary patterns

purpose: The purpose of this study was to investigate whether systemic lupus erythematosus (SLE) patients with interstitial lung disease represent a particular subset of patients characterized by the presence of clinical, serologic, and nailfold capillary patterns overlapping scleroderma. patients and methods: In 57 consecutive patients with SLE, a standardized detailed history was obtained and a physical examination performed, directed at signs and symptoms of connective tissue diseases, in particular scleroderma. Additionally, pulmonary function testing, chest radiography, radionuclide transit studies of the esophagus, nailfold capillary microscopy, and detailed serologic studies directed at the antigenic specificities of antinuclear antibodies were performed. Patients were divided into three groups based on the results of pulmonary function testing, i.e., normal lung function, restriction, or isolated impairment of diffusion. Clinical, serologic, and nailfold capillary microscopic findings were compared among these three groups. results: Twenty patients had normal lung function, 19 had restrictive lung function loss, and 9 had an isolated impairment of the diffusing capacity (T 1,CO). Patients with obstructive lung disease (n = 9) were excluded from analysis. Sclerodermatous changes of the hands were associated with a restrictive lung function pattern. Interstitial changes on chest radiograph were associated with isolated impairment of T 1,CO- Nailfold capillary abnormalities correlated with decreased T 1,CO and Dm, the component of T 1,CO representing the diffusing capacity of the alveolocapillary membrane. Antibodies to U1-RNA were associated with restrictive lung function and decreased T 1,CO. conclusion: We conclude that interstitial lung disease is present in a subset of SLE patients characterized by an increased prevalence of scleroderma traits and anti-(U1)RNA antibodies. Microvascular changes may contribute to the development of interstitial lung disease in SLE as well as in scleroderma.

The external respiration and gas exchange in space missions

Literature data and results of our own studies into an effect of micro- and macro-gravity on an external respiration function of man are presented. It is found that in cosmonauts following the 7–366 day space missions there is an enhanced tendency associated with an increased flight duration toward a decrease in the lung volume and breathing mechanics parameters: forced vital capacity of the lungs (FVC) by 5–25 percent, peak inspiratory and expiratory (air) flows (PIF, PEF) by 5–40 percent. A decrease in FVC appears to be explained by a new balance of elastic forces of the lungs, chest and abdomen occuring in microgravity as well as by an increased blood filling and pulmonary hydration. A decline of PIF and PEF is probalbly resulted from antigravitational deconditioning of the respiratory muscles with which a postflight decreased physical performance can in part be associated. The ventilation/perfusion ratios during orthostasis and +G Z and +G X accelerations are estimated. The biophysical nature of developing the absorption atelectases on a combined exposure to accelerations and 100% oxygen breathing is confirmed. A hypothesis that hypervolemia and pulmonary congestion can increase the tendency toward the development of atelectases in space in particular during pure oxygen breathing is suggested. Respiratory physiology problem area which is of interest for space medicine is defined. It is well known that due to present-day technologic progress and accomplishments in applied physiology including applied respiration physiology there currently exist sophisticated technical facilities in operation maintaining the life and professional working capacity of a man in various natural environments: on Earth, under water and in space. By the way, the biomedical involvement in developing and constructing such facilities has enabled an accumulation of a great body of information from experimental studies and full-scale trails to examine the effects of the changed environments both and its individual systems including an external respiration function. In this case, it should be remembered that the external respiration system has some physiological and morphological properties due to which the body systems are particularly subjected to environmental effects. Thus, according to figurative comparison by Evald Veible a contact area of the lungs with an external environment i.e. an alveolar surface is large and equaled approximately to tennis-court size, as the alveolocapillary membrane thickness is negligible and amounts to one fiftieth of a writing-paper sheet [1]. From this it follows that such a fine and highly organized structure must be extremely dependent upon any external exposures including gravitational ones since from the physical viewpoint of physics the lungs represent a quasiconical three-dimensional elastic body suspended in the thoracic cavity and in which there occur the gravity-induced internal tensions incrementing in a base-to-apices direction. As a result of these tensions, in the lungs various physical gradients: hydrostatic, pleural and transpulmonary pressures, pulmonary time constant, vertical gradient of the volume and structure of alveoli, etc. are developed.

Clinical utility of non invasive methods in the evaluation of scleroderma lung in pediatric age.

Lung involvement in children affected with Systemic Sclerosis (SSc) has been studied. We used ventilation and perfusion scans and compared the results to those obtained with traditional pulmonary function tests. The vascular pulmonary area was examined with a gama-camera after infusion of 99mTc microspheres, while the alveolo-capillary membrane and the airways were investigated after administration of a radioaerosol, (99mTc DTPA). Pulmonary function tests revealed either alteration of the airways or a considerable involvement of the alveolo-capillary membrane in two patients. On the other hand ventilation scan showed airways alterations and a severe decrease of the alveolocapillary permeability in all patients. Our study indicates that ventilation scans may be useful in the diagnosis of early modifications of the lung function also in paediatric age and may complement the data obtained from traditional function tests.

Pulmonary diffusion limitation after prolonged strenuous exercise

To determine the effect of strenuous prolonged exercise on alveolo-capillary membrane diffusing capacity, 11 marathon runners aged 37 ± 7 years (mean ± SD) were studied before and during early recovery (28 ± 14 min) from a marathon race. Lung capillary blood volume (Vc) and the alveolo-capillary diffusing capacity (Dm) were determined in a one-step maneuver by simultaneous measurements of CO and NO lung transfer (D l CO and D l NO, respectively) using the single breath-holding method. After the race, both D l CO and D l NO were significantly decreased in all subjects − 10.9 ± 4.8%, P < 10 −4 and −29.0 ± 11.1%, P < 10 −4, respectively). The mean value of the derived Dm CO decreased by −29.3 ± 11.1 %, whereas Vc had no entirely returned to control resting value. Although these results do not indicate the detailed mechanism involved, interstitial lung fluid was suspected to accumulate, particularly in alveoli, during the race. We concluded that the high overall work load and the extended duration of the exercise both contributed to a transient change in the structure of the alveolo-capillary membrane thereby affecting the diffusing capacity of the alveolo-capillary membrane.

The Effect of Respiratory Disorders on Clinical Pharmacokinetic Variables

Respiratory disorders induce several pathophysiological changes involving gas exchange and acid-base balance, regional haemodynamics, and alterations of the alveolocapillary membrane. The consequences for the absorption, distribution and elimination of drugs are evaluated. Drug absorption after inhalation is not significantly impaired in patients. With drugs administered by this route, an average of 10% of the dose reaches the lungs. It is not completely clear whether changes in pulmonary endothelium in respiratory failure enhance lung absorption. The effects of changes in blood pH on plasma protein binding and volume of distribution are discussed, but relevant data are not available to explain the distribution changes observed in acutely ill patients. Lung diffusion of some antimicrobial agents is enhanced in patients with pulmonary infections. Decreased cardiac output and hepatic blood flow in patients under mechanical ventilation cause an increase in the plasma concentration of drugs with a high hepatic extraction ratio, such as lidocaine (lignocaine). On a theoretical basis, hypoxia should lead to decreased biotransformation of drugs with a low hepatic extraction ratio, but in vivo data with phenazone (antipyrine) or theophylline are conflicting. The effects of disease on the lung clearance of drugs are discussed but clinically relevant data are lacking. The pharmacokinetics of drugs in patients with asthma or chronic obstructive pulmonary disease are reviewed. Stable asthma and chronic obstructive pulmonary disease do not appear to affect the disposition of theophylline or beta 2-agonists such as salbutamol (albuterol) or terbutaline. Important variations in theophylline pharmacokinetics have been reported in critically ill patients, the causes of which are more likely to be linked to the poor condition of the patients than to a direct effect of hypoxia or hypercapnia. Little is known regarding the pharmacokinetics of cromoglycate, ipratropium, corticoids or antimicrobial agents in pulmonary disease. In patients under mechanical ventilation, the half-life of midazolam, a new benzodiazepine used as a sedative, has been found to be lengthened but the underlying mechanism is not well understood. Pulmonary absorption of pentamidine was found to be increased in patients under mechanical ventilation. Pharmacokinetic impairment does occur in patients with severe pulmonary disease but more work is needed to understand the exact mechanisms and to propose proper dosage regimens.

Transfer of 99mTc DTPA and bronchoalveolar lavage findings in patients with asymptomatic extrinsic allergic alveolitis.

An investigation was performed to determine whether symptom free patients with previously diagnosed extrinsic allergic alveolitis had signs of inflammation in the lung. Pulmonary clearance of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (DTPA) was measured in seven patients with a history of extrinsic allergic alveolitis but with no symptoms at the time of the study and in 12 control subjects. Monoexponential clearance curves were obtained in all 12 control subjects. In contrast, lung clearance was abnormal in five of the seven patients: biexponential clearance curves were noted in four and an abnormally rapid monoexponential curve in one. Bronchoalveolar lavage was performed in all patients. Fluid from the second and third aliquots showed increased concentrations of albumin and urea in fluids from the patients, suggesting increased plasma leakage through the alveolocapillary membranes. More eosinophils and more eosinophil cationic protein were also found in the lavage fluid from the patients. The trend towards increased numbers of eosinophils in patients with abnormal lung clearance of DTPA suggests that this may be due to a continuing inflammatory reaction. Lung inflammation was also suggested by the fact that less leukotriene B4 was secreted by cultured alveolar macrophages obtained from patients than by control macrophages. It is concluded that symptom free patients with previous extrinsic allergic alveolitis have continuing alveolar disease as shown by lung clearance and lavage findings.

Pulmonary diffusing capacity disturbances are related to nailfold capillary changes in patients with Raynauds's phenomenon with and without an underlying connective tissue disease

purpose: The aim of this study was to evaluate whether pulmonary microvascular damage is part of a more generalized involvement of the microvasculature in the spectrum of scleroderma (Scl)-like syndromes.patients and methods: We studied four groups of patients, all with Raynaud's phenomenon (RP), distinguished by the extent and nature of their underlying connective tissue disease. Twenty-two patients had primary RP (pRP), another 22 patients had RP and an undifferentiated connective tissue disease (uCTD), 15 patients had Scl, and eight patients had the CREST syndrome (CREST). Pulmonary vascular damage in these groups was assessed by measuring damage in these groups was assessed by measuring the pulmonary diffusing capacity (T1,CO) and its components: the diffusing capacity of the alveolocapillary membrane (Dm) and the pulmonary capillary blood volume (Vc). Results were compared with morphologic abnormalities of the nailfold capillaries, as determined by nailfold capillary microscopy, and related to the presence of antinuclear antibodies.results: Vc was below normal in 38% and 43% of patients with pRP and uCTD, respectively (versus 52% in patients with Scl or CREST combined). In contrast, Dm was below normal in only 5% and 26% of patients with pRP and uCTD, respectively (versus 61% in patients with Scl or CREST combined). In patients with Scl and CREST, Dm was significantly decreased as compared with the former groups (p <0.01). Dm was also the pulmonary function parameter that correlated most strongly with both nailfold capillary abnormalities and the presence of antinuclear antibodies, whereas Vc did not.conclusion: Early pulmonary involvement in Scl syndromes is functionally characterized by a lowered Dm, correlating with morphologic changes of the nailfold capillaries. Decreased Vc is probably a reflection of RP of the pulmonary vasculature.

Pulmonary diffusing capacity: implications of two-phase blood flow in capillaries

The classical view of oxygen (O 2) uptake in pulmonary capillaries assumes implicitly that capillary blood can be regarded as a continuous homogeneous hemoglobin solution. In this study a theoretical model was used to examine the role played by the particulate (two-phase) nature of blood on pulmonary oxygen exchange. Red cells were modelled as discrete hemoglobin (Hb) containing spheres flowing in single file suspension through a cylindrical capillary surrounded by a uniform annulus of alveolar tissue. The model accounted for the free diffusion of O 2 from alveolar air space through tissue and plasma, free and Hb facilitated diffusion of O 2 inside red cells, and the intracellular kinetics of O 2-Hb binding. Oxygen uptake was driven by a specified O 2 tension at the alveolar surface. The computed pulmonary diffusing capacity (D l O 2 ) decreased with increasing spacing (L s) between red cells. The reduction in D l O 2 with increasing L s was marshalled more by a reduction in membrane diffusing capacity (D m O 2 ), than by the reduction in erythrocyte diffusing capacity (De O 2 ). The dependence of D m O 2 on cell spacing stemmed from the manner in which O 2 flowed across the alveolar surface into the discrete sinks (red cells) within the capillaries. The degree to which L s influenced D m O 2 was dependent on tissue and plasma layer thickness relative to red cell dimensions. The results indicate that the functional area of the alveolo-capillary membrane for O 2 exchange depends on the red cell content of capillaries. Thus, D m O 2 is not indicated solely by the morphology of the exchange apparatus (and physical parameters), but has functional determinants as well.

Effect of change in particle number on pulmonary clearance of aerosolized 99mTc-DTPA.

Pulmonary clearance (PCl) of inhaled aerosolized 99mTc-diethylenetriamine pentaacetic acid (DTPA) across the alveolocapillary membrane is diffusion limited. Therefore, if the mixing of the 99mTc-DTPA in the aqueous hypophase underlying surfactant is slow or incomplete or if there were no hypophase, an increase in the alveolar surface area occupied by 99mTc-DTPA particles would increase the absorption rate. The aim of this study was to examine whether there is an effect on PCl of changing the number of inhaled particles. The change in particle number was accomplished by a setup of four parallel jet nebulizers feeding a central delivery chamber of 400 cm3. We performed two kinds of experiments in eight healthy nonsmokers between 28 and 52 yr of age. In the first experiment, 99mTc-DTPA in saline was nebulized in one nebulizer, while saline was nebulized in the other three. In the second experiment the number of inhaled particles containing 99mTc-DTPA was increased by a factor of four by nebulizing 99mTc-DTPA in saline in all four nebulizers simultaneously. Increasing the number of inhaled 99mTc-DTPA particles caused an increase in PCl of 24.2% (P less than 0.01). We conclude that there is a slight but significant effect of changing the number of DTPA particles on PCl and that this is probably due to an uneven mixing of the 99mTc-DTPA in the aqueous hypophase underlying the surfactant lining and the alveoli.

Effect of maternal exposure to smoke on gas diffusion capacity in neonatal rat

Offspring of control and experimental (chronically exposed to whole cigarette smoke) rats were sacrificed on 15th postnatal day. Pulmonary tissues were processed for quantitative electron microscopic analyses. Arithmetic and harmonic mean thicknesses were directly measured and diffusion capacity was derived for separate layers (tissue, plasma, erythrocyte) and the entire lung. Experimental offspring showed a greater volume density of interstitium in parenchyma ( P < 0.04), arithmetic ( P < 0.05) and harmonic ( P < 0.009) mean thicknesses. Diffusion capacities for lungs of both animal groups, however, were similar (0.00543 and 0.0054 cm 3 O 2 · min −1 · mm Hg −1 · g body weight −1 for control and experimental lungs respectively). Experimental tissue appeared better adapted for optimal exchange of gases ( P < 0.05), as indicated by corrugation index (ratio between arithmetic and harmonic mean thicknesses) than for the control counterpart. In spite of induced alterations in several developmental processes by a presently used experimental procedure, tissue capacity for transport of gases was not significantly changed in either the alveolo-capillary membrane or the entire lung.

Elevated Lactate Dehydrogenase Values in Patients with Pneumocystis carinii Pneumonia

We investigated the source of elevated serum lactate dehydrogenase (LDH) levels in seven patients with Pneumocystis carinii pneumonia (PCP) by analyzing blood and bronchoalveolar lavage (BAL) albumin (ALB) and LDH, with isoenzyme fractionation. Four patients with non-PCP lung disease served as control subjects. In PCP patients, BAL LDH was sixfold higher, and BAL ALB, fourfold higher than in the non-PCP patients. The increased LDH/ALB in BAL as compared to serum, in addition to a BAL isoenzyme pattern characteristic of lung, suggest that BAL LDH arises from a pulmonary source. We postulate that the high correlation observed between BAL and serum LDH (r = 0.93, p less than 0.001) reflects backflow of pulmonary-derived LDH into the blood through an alveolocapillary membrane (ACM) compromised by PCP. Furthermore, a comparison of BAL LDH/ALB for each isoenzyme with the same serum ratio showed less backflow for the cationic isoenzymes. The ACM appears to sieve proteins on an electrical basis which may account for the LDH isomorphic pattern observed in the serum of PCP patients.

Natural course of bleomycin-induced pneumonitis. A follow-up study.

In this study, long-term pulmonary complications of bleomycin were evaluated in 8 patients with bleomycin-induced pneumonitis (BIP). The lung function parameters: VC, alveolar volume, transfer factor for carbon monoxide of the lungs, diffusing capacity of the alveolocapillary membrane, and pulmonary capillary blood volume were studied in all patients for as long as 2 yr after the development of BIP. Perfusion scans with 133Xe and 99mTc were performed in these patients 2 yr after BIP developed. We concluded that if a patient survives the acute event of BIP, the pulmonary symptoms and the changes in these lung function parameters are completely reversible.