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PubMed2007

Hyperoxia reduces bone marrow, circulating, and lung endothelial progenitor cells in the developing lung: implications for the pathogenesis of bronchopulmonary dysplasia.

Hyperoxia disrupts vascular and alveolar growth of the developing lung and contributes to the development of bronchopulmonary dysplasia (BPD). Endothelial progenitor cells (EPC) have been implicated in repair of the vasculature, but their role in lung vascular development is unknown. Since disruption of vascular growth impairs lung structure, we hypothesized that neonatal hyperoxia impairs EPC mobilization and homing to the lung, contributing to abnormalities in lung structure. Neonatal mice (1-day-old) were exposed to 80% O(2) at Denver's altitude (= 65% at sea level) or room air for 10 days. Adult mice were also exposed for comparison. Blood, lung, and bone marrow were harvested after hyperoxia. Hyperoxia decreased pulmonary vascular density by 72% in neonatal but not adult mice. In contrast to the adult, hyperoxia simplified distal lung structure neonatal mice. Moderate hyperoxia reduced EPCs (CD45-/Sca-1+/CD133+/VEGFR-2+) in the blood (55%; P < 0.03), bone marrow (48%; P < 0.01), and lungs (66%; P < 0.01) of neonatal mice. EPCs increased in bone marrow (2.5-fold; P < 0.01) and lungs (2-fold; P < 0.03) of hyperoxia-exposed adult mice. VEGF, nitric oxide (NO), and erythropoietin (Epo) contribute to mobilization and homing of EPCs. Lung VEGF, VEGF receptor-2, endothelial NO synthase, and Epo receptor expression were reduced by hyperoxia in neonatal but not adult mice. We conclude that moderate hyperoxia decreases vessel density, impairs lung structure, and reduces EPCs in the circulation, bone marrow, and lung of neonatal mice but increases EPCs in adults. This developmental difference may contribute to the increased susceptibility of the developing lung to hyperoxia and may contribute to impaired lung vascular and alveolar growth in BPD.

Aging↗
PubMed1996

Unilateral smoke inhalation in sheep: effect on left lung lymph flow with right lung injury.

We previously reported that smoke inhalation to the right lung will result in damage to the air-insufflated left lung. In this study we confirm these findings and determine whether this injury is associated with an elevation in lung lymph flow and pulmonary microvascular permeability to protein as indexed by changes in reflection coefficient. Sheep (n = 12) were surgically prepared by placement of a Swan-Ganz catheter and pneumatic occluders on all pulmonary veins and the left pulmonary artery. The left lung lymphatic was selectively cannulated as shown previously (Y. Kikuchi, H. Nakazawa, and D. Traber. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R943-R947, 1995). All afferent lymphatics from the right lung were severed, and the right pulmonary ligament was sectioned. The caudal end of the lymph node was sectioned to remove systemic lymph contamination. The sheep were studied in the unanesthetized state 7 days later. To ensure that lymph flow was exclusively from the left lung (QLL), right pulmonary microvascular pressure was increased, a procedure that resulted in little or no change in QLL, as was previously shown. The sheep were then anesthetized, and a Carlens tube was positioned to allow separate ventilation of the right and left lung. The right lungs of five sheep and the left lungs of two sheep were insufflated with cotton smoke. Insufflation of the left lung with cotton smoke produced a fourfold increase in QLL that began 4 h after insult. Insufflation of the right lung with smoke led to a doubling of QLL that began 12 h after insult. Changes in QLL were associated with increased microvascular permeability, as indexed by the reflection coefficient. Control sheep (air insufflated into both lungs, n = 5) showed no change in QLL. Injury to the right lung resulted in damage to the left air-insufflated lung, suggesting a hematogenous mediation of the response.

Animals↗
PubMed1996

Regulation of lung expansion and lung growth before birth.

Fetal lung growth depends on the degree to which lungs are distended with luminal liquid. Fetal lungs are highly distended such that mean luminal volume exceeds the static relaxation volume. This high level of expansion is maintained by fetal breathing movements and by resistive effects of the upper airway during apnea; both factors oppose lung recoil. Mechanical stress in lung and other tissues stimulates cell division and tissue remodeling. Potential transduction mechanisms involve direct effects of cellular tension and mediation of locally released mitogenic factors. Further studies are required to further define links between lung tissue stress, increased growth, structural remodeling, and the endocrine environment. A common cause of fetal lung hypoplasia is a sustained reduction in mean lung expansion. Studies of mechanisms controlling fetal lung expansion have led to insights into the etiology of fetal lung hypoplasia and how it may be remedied in utero. Fetal lung hypoplasia can have long-lasting effects on postnatal lung function, as airway and alveolar formation may be compromised. Preterm birth may also result in incomplete structural development of the lungs as it shortens the period of increased intrauterine lung expansion.

Animals↗
PubMed2000

Biochemical and morphological changes in lung tissue and isolated lung cells of rats induced by short-term nitrogen dioxide exposure.

To investigate the effects of repeated exposure to nitrogen dioxide (NO2) on antioxidant enzymes in lung tissue and isolated lung cells, rats were continuously exposed to 20 mg/m3 NO2 (10.6 ppm) for 4 days. The activities of glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), and glutathione peroxidase (GSHPx) were measured in the cytosolic fraction of lung tissue of both control and NO2-exposed rats as well as in isolated alveolar macrophages (AMs) and type II cells. Qualitative and quantitative changes in AM and type II cells were studied by electron microscopy and by morphometric analyses using enzyme and immunohistochemistry. NO2 exposure resulted in significantly increased pulmonary activities of G6PDH, GR, and GSHPx, both expressed per lung and per gram of lung weight. Morphometric data show that NO2 exposure significantly increased the number of type II cells, predominantly in the centriacinar region, indicating proliferation of epithelium following cellular injury. Type II cells in lungs of NO2-exposed rats had a squamous, less cuboidal appearance with more lamellar bodies compared to type II cells in lungs of control rats. Compared to control lungs, a higher number of macrophages could be isolated from NO2-exposed lungs, while numbers of type II cells isolated from lungs of control and NO2-exposed rats were the same. Isolated type II cells from control and NO2-exposed rats were polymorphic, with a small number of lamellar bodies and without polarity. Isolated macrophages were rounded and contained many filopodia. NO2 exposure caused increases in the activities of G6PDH and GSHPx in isolated type II cells and of GSHPx in isolated macrophages, when expressed per number of cells. Macrophages and type II cells isolated from control and NO2-exposed rats and re-exposed in vitro to NO2, showed no differences in phagocytosis and viability features. Our results indicate that NO2-induced increases in pulmonary antioxidant enzymes are also reflected in isolated AM and type II cells. Since these lung cells do not display a decreased sensitivities toward an in vitro NO2 exposure, overall increase in antioxidant enzyme activities do not seem to play the most pivotal role in controlling cellular NO2 sensitivity and oxidant defence. Combined data from biochemical, morphological, and morphometric analyses of lungs and lung cells suggest that lung cell and tissue oxidant sensitivity and defence largely depends on the cell and tissue organisation, i.e., cell numbers and morphology as well as the ratio of surface area to cytoplasmic volume.

Animals↗
PubMed1998

Stimulation of lung growth by tracheal obstruction in fetal sheep: relation to luminal pressure and lung liquid volume.

Obstruction of the fetal trachea causes liquid to accumulate within the future airways, which is a potent stimulus for lung growth. Our aim was to determine the relationship between the increase in fetal lung growth after tracheal obstruction and the increases in lung liquid volume and tracheal pressure to better understand the mechanisms involved in the growth response. The effects of 4 and 10 d of tracheal obstruction on lung DNA and protein contents and DNA synthesis rates were determined; these data were combined with data collected previously after 2 and 7 d of tracheal obstruction. Fetal lung liquid volumes and secretion rates were measured before (d 0) and on d 1, 2, 4, 7, and 10 after tracheal obstruction; fetal tracheal pressures were monitored throughout this period. Tracheal pressures increased from 2.9 +/- 0.8 mm Hg (control) to 4.3 +/- 0.4 mm Hg within 1 d of tracheal obstruction and remained at this elevated level for the duration of the obstruction period. Lung liquid volume increased progressively from 24.7 +/- 1.1 mL/kg on d 0 to 97.3 +/- 15.2 mL/kg at d 7 of tracheal obstruction, but had not increased further by d 10. Tracheal obstruction significantly increased lung DNA and protein contents above control values; over the 10-d period the increase in lung DNA content was closely related (r = 0.99) to the increase in lung liquid volume, but not to the increase in tracheal pressure. DNA synthesis rates were increased at 4 d of tracheal obstruction (by 66%) but had returned to control levels by d 10. We conclude that: 1) the mechanisms responsible for the acceleration in lung growth induced by tracheal obstruction are most active on d 2, remain active at a reduced level on d 4 and 7, and have returned to control levels by d 10; and 2) the increase in lung DNA content during tracheal obstruction (d 2-7) is closely related to the increase in lung liquid volume, but not to the increase in intraluminal pressure. Thus, we suggest that an increase in lung expansion is one of the primary factors responsible for the acceleration in fetal lung growth induced by tracheal obstruction.

Airway Obstruction↗
PubMed2006

IL-1 alpha causes lung inflammation and maturation by direct effects on preterm fetal lamb lungs.

Intra-amniotic endotoxin induces IL-1, causes chorioamnionitis, lung inflammation, lung injury and lung maturation in preterm lambs. Intra-amniotic IL-1alpha also causes chorioamnionitis, lung inflammation and lung maturation. We asked if IL-1alpha effects on the preterm lung are mediated by direct signaling to the lung rather than by indirect effects from the chorioamnionitis. To study IL-1 effects independently of chorioamnionitis, the lungs and the amniotic fluid were surgically separated in fetal sheep by diverting fetal lung fluid via a tracheostomy tube to a sialastic bag. A mini-osmotic pump delivered an intratracheal infusion of recombinant sheep IL-1alpha (10 microg) or saline (control) over 24 h. Preterm lambs were delivered 1d or 7d after the start of the infusion at 124d gestational age (Term = 150d). IL-1alpha recruited inflammatory cells and increased pro-inflammatory cytokine mRNA expression in the fetal lungs. Compared with controls, IL-1alpha did not alter lung antioxidant enzyme activity or alveolar numbers. IL-1alpha had minimal effects on the mRNA or protein expression of proteins essential for vascular development. IL-1alpha induced large increases in alveolar surfactant saturated phosphatidylcholine and increased lung gas volumes. Lung inflammation and maturation result from direct exposure of the fetal lung to a single cytokine - IL-1alpha.

Animals↗
PubMed1997

Talc and amosite/crocidolite preferentially deposited in the lungs of nonoccupational female lung cancer cases in urban areas of Japan.

To analyze the correlation between asbestos lung burden and lung cancer, lungs of 211 female cases with and without lung cancer were examined. Phase-contrast microscopic (PCM) counting of ferruginous (FBs) and uncoated fibers (UFs), which had length longer than 5 microns and aspect ratios greater than 3:1, revealed a significantly higher level of FBs plus UFs in urban lung cancer cases than urban non-lung cancer cases (1380.5 vs. 550.3; p < 0.001). No difference was noted between rural lung cancer and non-lung cancer cases. Analytical electron microscopic studies identified various kinds of mineral fibers with an aspect ratio greater than 3:1 in the lung tissue including chrysotile, actinolite/tremolite, amosite/crocidolite, fibrous talc, mica, silica, iron, wollastonite, chlorite, kaoline, and others. The most frequently detected fibers were thin, short chrysotile fibers, most of which could not be found by PCM, followed by relatively thick, long actinolite/tremolite fibers, fibrous talc, and in a smaller number, amosite/crocidolite of intermediate length and width. Amosite/crocidolite and fibrous talc counts in urban lung cancer cases were greater than those of urban non-lung cancer cases, rural lung cancer, and rural non-lung cancer cases; these findings were consistent with PCM analysis. Therefore, it is suggested that fibers detected in PCM observation may be mainly amosite/crocidolite with some parts fibrous talc and that fibrous talc in urban environments may be another candidate for carcinogenic or cocarcinogenic factors of female lung cancer.

Adult↗
PubMed2002

[A new medical education using a lung sound auscultation simulator called "Mr. Lung"].

We developed a lung sound auscultation simulator "Mr. Lung" in 2001. To improve the auscultation skills of lung sounds, we utilized this new device in our educational training facility. From June 2001 to March 2002, we used "Mr. Lung" for our small group training in which one hundred of the fifth year medical students were divided into small groups from which one group was taught every other week. The class consisted of ninety-minute training periods for auscultation of lung sounds. At first, we explained the classification of lung sounds, and then auscultation tests were performed. Namely, students listened to three cases of abnormal or adventitious lung sounds on "Mr. Lung" through their stethoscopes. Next they answered questions corresponding to the portion and quality of the sounds. Then, we explained the correct answers and how to differentiate lung sounds on "Mr. Lung". Additionally, at the beginning and the end of the lecture, five degrees of self-assessment for the auscultation of the lung sounds were performed. The ratio of correct answers for lung sounds were 36.9% for differences between bilateral lung sounds, 52.5% for coarse crackles, 34.1% for fine crackles, 69.2% for wheezes, 62.1% for rhonchi and 22.2% for stridor. Self-assessment scores were significantly higher after the class than before. The ratio of correct lung sound answers was surprisingly low among medical students. We believe repetitive auscultation of the simulator to be extremely helpful for medical education.

Auscultation↗
PubMed2000

[Assessment of noninvasive therapy in lung cancer using lung perfusion images].

The purpose of this prospective study was to follow the changes in functional parameters of radionuclide lung perfusion scans and their role in prognostication of lung cancer cases after noninvasive therapy. We studied 91 patients of lung cancer treated with chemotherapy and/or radiotherapy during 1993 to 1997 in our hospital. Lung perfusion scans were acquired pre and post-therapy. An index of lung perfusion, called Improvement Ratio (IR) was defined as a change in the perfusion of diseased lung as a result of treatment. IR was calculated by the following equation under the assumption that perfusion of contralateral lung remained unaffected. [formula: see text] where Q and Q' are pulmonary arterial blood flow pre and post therapy respectively, p is perfusion ratio of diseased lung before therapy and q is that after therapy. We further studied the relationship between IR and change in tumor size. The influence of tumor location, histopathological diagnosis and prognosis of lung cancer were correlated with this newly defined index. IR in the group of patients with complete response or partial response was significantly higher than in those with poor response (2.72 +/- 0.78 versus 0.99 +/- 0.09, p < 0.05). There was no statistical difference between the group with and without radiotherapy. The score was significantly higher for patients with hilar disease compared to those with peripheral lesions (2.80 +/- 0.83 versus 1.02 +/- 0.03, p < 0.05). Similarly, patients with small cell lung cancer depicted higher values of IR than non-small cell lung cancer (3.36 +/- 1.10 versus 1.06 +/- 0.07, p < 0.05). All those subjects who showed IR > 1 had longer survival time than those with IR < 1 (p < 0.05). It is suggested that improvement in the perfusion of diseased lung predicted better prognosis. We conclude that the evaluation of physiological parameters during therapy using lung perfusion scanning, in addition to lesion size assessment will contribute to the comprehensive follow-up of lung cancer.

Adult↗
PubMed2000

Thoracoscopy versus open lung biopsy in the diagnosis of interstitial lung disease: a randomised controlled trial.

BACKGROUND: Some patients with diffuse lung disease require a lung biopsy for diagnosis. This study is aimed to compare the clinical results and the efficacy of video-assisted thoracoscopic lung biopsy with the open lung biopsy method for the diagnosis of interstitial lung disease. From January 1996 to December 1998, 61 patients were referred for diagnostic lung biopsy. Thirty two patients were randomly allocated to have a thoracoscopic lung biopsy and twenty nine had an open lung biopsy. Subsequently, various factors were analyzed and compared in both groups. RESULTS: There was no difference between the groups in age and pulmonary function test. Median operative time was 45 minutes for the thoracoscopic biopsies and 60 minutes for the open biopsies (P = 0.009). Median amount of analgesia (Demerol) in the first 24 hours postoperatively was 75 mg. for thoracoscopic biopsies and 150 mg. for open biopsies (P < 0.001). Median duration of insertion of a chest tube in days and 24 hours of pleural drainage was not statistically significant between the two groups. Duration of hospital stay was significantly less for the thoracoscopic biopsy (3 days) compared with an open biopsy (5 days) (P < 0.001). The diagnostic yield of each method was comparable (thoracoscopic biopsy 31/32; open biopsy 27/29) (P = 0.3). Complications occurred in 6/29 of patients undergoing open biopsies and 3/32 patients undergoing thoracoscopic lung biopsies (p = 0.28). There were 2 deaths among patients who had an open lung biopsy. CONCLUSION: Thoracoscopic lung biopsy has some clinical advantages over open biopsy. These findings suggest that thoracoscopic lung biopsy is an acceptable alternative to open lung biopsy for the diagnosis of diffuse interstitial lung diseases.

Adult↗
PubMed2003

Reproducibility of lung tumor position and reduction of lung mass within the planning target volume using active breathing control (ABC).

PURPOSE: The active breathing control (ABC) device allows for temporary immobilization of respiratory motion by implementing a breath hold at a predefined relative lung volume and air flow direction. The purpose of this study was to quantitatively evaluate the ability of the ABC device to immobilize peripheral lung tumors at a reproducible position, increase total lung volume, and thereby reduce lung mass within the planning target volume (PTV). MATERIALS AND METHODS: Ten patients with peripheral non-small-cell lung cancer tumors undergoing radiotherapy had CT scans of their thorax with and without ABC inspiration breath hold during the first 5 days of treatment. Total lung volumes were determined from the CT data sets. Each peripheral lung tumor was contoured by one physician on all CT scans to generate gross tumor volumes (GTVs). The lung density and mass contained within a 1.5-cm PTV margin around each peripheral tumor was calculated using CT numbers. Using the center of the GTV from the Day 1 ABC scan as the reference, the displacement of subsequent GTV centers on Days 2 to 5 for each patient with ABC applied was calculated in three dimensions. RESULTS: With the use of ABC inspiration breath hold, total lung volumes increased by an average of 42%. This resulted in an average decrease in lung mass of 18% within a standard 1.5-cm PTV margin around the GTV. The average (+/- standard deviation) displacement of GTV centers with ABC breath hold applied was 0.3 mm (+/- 1.8 mm), 1.2 mm (+/- 2.3 mm), and 1.1 mm (+/- 3.5 mm) in the lateral direction, anterior-posterior direction, and superior-inferior direction, respectively. CONCLUSIONS: Results from this study indicate that there remains some inter-breath hold variability in peripheral lung tumor position with the use of ABC inspiration breath hold, which prevents significant PTV margin reduction. However, lung volumes can significantly increase, thereby decreasing the mass of lung within a standard PTV.

Adult↗
PubMed2002

Results of an artificial-lung survey to lung transplant program directors.

BACKGROUND: Lung transplantation is the only treatment for patients with end-stage lung disease. However, the scarcity of donor organs illustrates the need for alternatives. Recent success in the use of ventricular assistance has stimulated research in technology designed as a bridge to lung transplantation. Some laboratories have demonstrated significant advances in the development of artificial lungs, and clinical applications are on the horizon. In preparation, we sought to gather information from the lung transplant community regarding issues related to testing and potential trials of artificial lungs. METHODS: We constructed a survey and distributed it to lung transplant program directors recognized by the United Network for Organ Sharing. Topics included required animal studies, preferred designs, logistics of clinical trials, and patient diagnoses most appropriate for such a trial. RESULTS: The 31 programs responding to the survey performed 72% of all lung transplants in the United States in 1999. Ninety-seven percent supported a Phase I trial using an artificial lung as a bridge to lung transplantation. Additionally, 58% specifically supported a trial in which organ allocation would be prioritized to enrolled patients. Idiopathic pulmonary fibrosis was the diagnosis thought most appropriate for inclusion in initial clinical trials. CONCLUSIONS: Widespread support exists for the development and use of an artificial lung as a bridge to lung transplantation. Information from transplant centers regarding device design and application can influence laboratories developing artificial lungs, and such communication will be essential as this technology progresses from the bench-top to the bedside.

Animals↗
PubMed1995

Changes in regional lung impedance after intravenous histamine bolus in dogs: effects of lung volume.

We measured the effect of lung volume on the time course of regional lung input impedance (ZA) after bolus intravenous administration of 2 mg of histamine in seven open-chest dogs using alveolar capsule oscillators. ZA (24-200 Hz) was obtained during apnea at constant lung volume every 2 s for 80 s at lung inflation pressures of 0.1, 0.2, 0.3, 0.5, 0.7, and 1.0 kPa. Local airway resistance (RA) and elastance of the local lung region were calculated by fitting a four-parameter model to the measured ZA. Total lung resistance and lung elastance were also calculated from tracheal pressure and flow measured during mechanical ventilation (0.3 Hz) just before and after each set of ZA measurements. We found the histamine-induced changes in both lung resistance and lung elastance to decrease with increasing lung volume. RA also showed a large negative dependency on lung volume, and the variation between different RA measurements became markedly increased as lung volume decreased. In contrast, local airway elastance was essentially unaffected by lung volume. These results support the idea that parenchymal tethering of the very distal airways impedes their narrowing during bronchoconstriction. They also indicate that reduced parenchymal tethering causes airway narrowing to become markedly more inhomogeneous.

Airway Resistance↗
PubMed1994

Lung oxidant injury in a model of lung storage and extended reperfusion.

Donor lungs for transplantation are susceptible to "preservation" injury during both storage and postimplantation reperfusion. We investigated whether lung dysfunction seen after storage and reperfusion was associated with any biochemical hallmarks of direct cellular oxidant injury to lipid, protein, or DNA. Heart/lung blocks were extracted from adult rats following pulmonary vascular flush. Lungs were either perfused immediately ex vivo for 2 h with deoxygenated venous rat blood or were stored at 10 degrees C for 13 h before perfusion. Stored lungs had increased airway pressure, pulmonary vascular shunt fraction, wet/dry weight ratio, and parenchymal hemorrhage after perfusion but no change in pulmonary artery pressure compared with immediately perfused lungs. Hypothermic storage caused no biochemical changes in lung tissue. Perfusion of fresh or stored lungs resulted in lipid peroxidation and loss of nonprotein reduced sulfhydryls; sulfhydryl loss was threefold higher in lungs stored before perfusion compared with freshly perfused lungs. Reperfusion of stored, not fresh, lungs was associated with DNA damage. No loss of protein sulfhydryls occurred following lung perfusion. We conclude that DNA damage, loss of reduced nonprotein sulfhydryls, and lipid peroxidation during reperfusion of stored lungs may be responsible for physiologic lung dysfunction.

Animals↗
PubMed1990

Role of lung fluid volume in growth and maturation of the fetal sheep lung.

We studied the effects of alterations in lung fluid volume on growth and maturation of the fetal lung. In a chronic fetal sheep preparation, right fetal lung volume was decreased by drainage of lung fluid while the volume of the left lung was expanded by mainstem bronchus ligation leading to lung fluid retention. After an experimental period of 25 d (from 105 to 129 d of gestation, term = 145 d), the right (deflated) lung was significantly hypoplastic and contained less DNA than the controls; 175.15 +/- 55.18 vs. 346.77 +/- 61.97 mg, respectively; P less than 0.001. In contrast, the left (expanded) lung was significantly hyperplastic and contained more DNA than the controls; 390.74 +/- 103.53 vs. 238.85 +/- 33.32 mg, respectively; P = 0.001. Biochemical indices of lung maturation, including total phospholipids, phosphatidylcholine, and disaturated phosphatidylcholine content expressed per unit of tissue DNA, were no different when comparing the hypoplastic, hyperplastic, and control lungs. These findings demonstrate that fetal lung cell multiplication is influenced by local distension with lung fluid, while the biochemical maturation of fetal lung surfactant is under systemic control.

Animals↗
PubMed1986

Human chorionic gonadotropin in lung and lung tumors. Immunohistochemical study on unbalanced distribution of subunits.

To demonstrate unbalanced distribution of subunits of human chorionic gonadotropin (hCG) in the lung and lung tumors and to clarify its significance in differentiation and carcinogenesis of the lung, immunohistochemistry was performed on human fetus, infant, and adult lungs, and endocrine and nonendocrine tumors of the lung. Tissues were immunostained for alpha-subunits and for beta-subunits of glycoprotein hormones (hCG, luteinizing hormone, follicle stimulating hormone, and thyroid stimulating hormone), serotonin, and gastrin-releasing peptide. Immunoreactive alpha-subunit was first identified in endocrine-like cells at the 39th gestational week, and was found in all infant lungs and two-thirds of adult lungs. The hCG beta-immunoreactive cells were extremely rare in an adult lung, and were not found in fetus or infant lungs. The alpha-subunit-containing cells were present in neuroepithelial bodies, tumorlets, carcinoid tumors, and small cell carcinomas of the lung (SCCL). There were occasionally alpha-subunit-containing cells in non-SCCL but one of the carcinomas also contained many serotonin-positive and gastrin-releasing peptide-positive cells in the same region. All alpha-subunit-immunoreactive cells lacked immunoreactivity for beta-subunits of glycoprotein hormones, except some for hCG beta in one carcinoid tumor. Immunoreactive cells for isolated hCG beta appeared much more frequently in non-SCCL than in SCCL. Most non-SCCL containing hCG beta-positive cells did not show alpha-subunit-immunoreactivity. Thus, immunohistochemical distribution of hCG-subunits was unbalanced and hCG-subunits may be expressed through an independent mechanism, commonly in the lung and lung tumors. The significance of isolated alpha-subunit is further discussed in light of multidirectional differentiation of lung neoplasms (14, 17).

Adult↗
PubMed2001

Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

OBJECTIVE: To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. DESIGN: A prospective, randomized, controlled, in vivo animal laboratory study. SETTING: Animal research facility of a health sciences university. SUBJECTS: Forty-six New Zealand White rabbits. INTERVENTIONS: Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. MEASUREMENTS AND MAIN RESULTS: Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. CONCLUSIONS: Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and decreased lung damage. However, in this small-animal model of acute lung injury, an open lung strategy with deliberate hypercapnia was associated with significant hemodynamic instability.

Animals↗
PubMed2004

Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation.

OBJECTIVE: Although ventilation with small tidal volumes is recommended in patients with established acute lung injury, most others receive highly variable tidal volume aimed in part at normalizing arterial blood gas values. We tested the hypothesis that acute lung injury, which develops after the initiation of mechanical ventilation, is associated with known risk factors for ventilator-induced lung injury such as ventilation with large tidal volume. DESIGN: Retrospective cohort study. SETTING: Four intensive care units in a tertiary referral center. PATIENTS: Patients who received invasive mechanical ventilation for > or = 48 hrs between January and December 2001. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome of interest, acute lung injury, was assessed by independent review of daily digital chest radiographs and arterial blood gases. Ventilator settings, hemodynamics, and acute lung injury risk factors were extracted from the Acute Physiology and Chronic Health Evaluation III database and the patients' medical records. Of 332 patients who did not have acute lung injury from the outset, 80 patients (24%) developed acute lung injury within the first 5 days of mechanical ventilation. When expressed per predicted body weight, women were ventilated with larger tidal volume than men (mean 11.4 vs. 10.4 mL/kg predicted body weight, p <.001) and tended to develop acute lung injury more often (29% vs. 20%, p =.068). In a multivariate analysis, the main risk factors associated with the development of acute lung injury were the use of large tidal volume (odds ratio 1.3 for each mL above 6 mL/kg predicted body weight, p <.001), transfusion of blood products (odds ratio, 3.0; p < 0.001), acidemia (pH < 7.35; odds ratio, 2.0; p =.032) and a history of restrictive lung disease (odds ratio, 3.6; p =.044). CONCLUSIONS: The association between the initial tidal volume and the development of acute lung injury suggests that ventilator-associated lung injury may be an important cause of this syndrome. Height and gender should be considered when setting up the ventilator. Strong consideration should be given to limiting large tidal volume, not only in patients with established acute lung injury but also in patients at risk for acute lung injury.

Aged↗