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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung structure and function, and the effect of surfactant replacement, were studied in three animal models of adult respiratory distress syndrome (ARDS): surfactant depletion by repeated lung lavage, proteinaceous pulmonary edema induced by prolonged exposure to hyperoxia, and inoculation with hybridoma making an antibody to the hydrophobic surfactant-associated protein, SP-B. Surfactant replacement therapy restored normal gas exchange in respiratory failure induced by repeated lung lavage but was ineffective in animals with severe lung parenchymal lesions induced by hyperoxia or antibody to SP-B. Lung edema fluid from animals exposed to hyperoxia inhibited surfactant function in a concentration-dependent manner. These observations indicate that, in experimental ARDS, the effect of surfactant replacement depends on the type of animal model and, especially, on the degree of lung injury present at the time of therapy.
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PMID:Surfactant inactivation and surfactant replacement in experimental models of ARDS. 192 24

In spite of the development of various antibiotics, management of elderly patients with pneumonia remains an important problem. It is suggested that adult respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) often occur in elderly patients with pneumonia. Although neutrophils are suggested to be involved in the genesis of these conditions, details remain unknown. We demonstrated that a highly cytotoxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized from linoleate by human neutrophils, thus it was named leukotoxin. Leukotoxin was detected in lung lavages from patients with ARDS. In these lung lavages, increases in albumin concentration and angiotensin converting enzyme (ACE) activity were also observed. Similar results were observed in lung lavages from rats after exposure to hyperoxia for 60 hours in an experimental model of ARDS. Intravenous administration of leukotoxin (100 mumol/kg) caused lung edema. Albumin concentration and ACE activity were increased in lung lavages of rats receiving leukotoxin. In contrast, these changes were not observed in rats administered with linoleate. Furthermore, administration of leukotoxin (100 mumol/kg) caused coagulation abnormality, i.e., increase in fibrin-fibrinogen degradation products, decrease in fibrinogen, and prolongation of activated partial thromboplastin time and prothrombin time. Administration of linoleate did not induce these changes. It is indicated that O2- was produced by respiratory burst enzyme located in neutrophil plasma membrane, and that hydroxyl radicals derived from O2- by Fenton reaction were responsible for leukotoxin synthesis. From our results, leukotoxin, a product of hydroxyl radicals and linoleate, might be responsible for the genesis of ARDS and DIC.
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PMID:[Leukotoxin and pulmonary injury]. 238 90

The physiological, morphological, and morphometric findings of several lung injury models in baboons have been compared in the following six study groups: 1) initial injury with oleic acid followed by ventilation with 100% O2, 2) ventilation with 100% O2, 3) ventilation with 80% O2, 4) ventilation with 80% O2 followed by inoculation of Pseudomonas aeruginosa, 5) ventilation with 40% O2, and 6) normal nonventilated room-air-breathing animals. The animals were maintained for 11 days in an intensive care unit. Light microscopically, animals ventilated with 40 and 80% O2 showed mild lung injury, consisting mostly of an increase in alveolar macrophages in peribronchiolar sites and focal alveolar wall widening. The 100% O2-oleic acid, 100% O2, and 80% O2-Pseudomonas-treated baboons showed mixed exudative-reparative diffuse alveolar lesions. Ultrastructurally, the type II cells of these three groups had significantly altered morphology with aberrations of lamellar body configurations. Morphometric findings showed increases in type II and interstitial cells and decreases in type I and endothelial cells in these injured animals. A striking finding was that the physiological, morphological, and morphometric changes of an 80% O2-Pseudomonas insult was as injurious as 100% O2. This synergistic effect of hyperoxia and infection very likely reflects the most frequent evolution of adult respiratory distress syndrome in patients in intensive care units.
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PMID:O2- and pneumonia-induced lung injury. I. Pathological and morphometric studies. 275 63

Despite the wide range of insults that can lead to the development of ARDS, a common sequence of pathologic changes can be identified in the lung. These changes can be divided into three phases: the acute, or exudative, phase (up to 6 days), in which hyaline membranes are a characteristic feature; the subacute, or proliferative, phase (4 to 10 days), in which metaplasia of the alveolar lining cells and early evidence of fibrosis are seen; and the chronic phase (8 days and on), when organizing fibrosis is a major finding. Structural changes of chronic pulmonary hypertension are also found in the patients with ARDS of longer duration. The mechanism by which these pulmonary changes occur is unknown. Studies of experimental models of ARDS may offer the best opportunity to elucidate the mechanisms. For example, a single infusion of E. coli endotoxin into sheep mimics the pathophysiologic changes of ARDS, offering a model for study of the initial insult on the lung. In addition, animals exposed to high concentrations of oxygen also show morphologic changes similar to those seen in patients with ARDS. Whether the hyperoxia is responsible for such changes, or whether it potentiates the injury induced by some other insult, is not certain.
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PMID:Pathology of the adult respiratory distress syndrome. 333 56

Pulmonary influxed neutrophils have been suggested to be involved in the development of hyperoxia-induced lung injury. We recently revealed that a highly toxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized by human neutrophils, thus it was named leukotoxin. Because hyperoxia-induced lung injury is a model of adult respiratory distress syndrome (ARDS), this study was designed to investigate whether or not leukotoxin is involved in the genesis of pulmonary oxygen toxicity and ARDS. After exposure to hyperoxia for 60 h, rats showed acute pulmonary edema, which was evidenced by increased lung weight, albumin concentrations, and angiotensin-converting enzyme (ACE) activities in lung lavages. These changes were correlated with an increased number of neutrophils. We detected leukotoxin in lung lavages of rats after exposure to hyperoxia for 60 h by high performance liquid chromatography and gas-chromatography/mass spectrometry. After intravenous injection of leukotoxin (100 mumol/kg) to rats, acute edematous lung injury occurred showing increases in lung weight, lung lavage albumin concentrations, and lung lavage ACE activities. In the lung lavages obtained from 5 patients with ARDS, significant increases in albumin concentrations and ACE activities were observed compared with those from subjects without pulmonary disease. Moreover, considerable amounts of leukotoxin, 38.5 +/- 21.9 nmol/lung lavage, were observed in the lavages from patients with ARDS. These findings suggest that leukotoxin plays an important role in the genesis of acute edematous lung damage in pulmonary oxygen toxicity, and that leukotoxin also links with the development of lung injury observed in patients with ARDS.
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PMID:Existence of leukotoxin 9,10-epoxy-12-octadecenoate in lung lavages from rats breathing pure oxygen and from patients with the adult respiratory distress syndrome. 334 35

Alveolar macrophage accumulation and interstitial fibrin deposition are prominent in adult respiratory distress syndrome and chronic interstitial lung diseases. The role of alveolar macrophages in the initiation of fibrin deposition and lung injury in these diseases is uncertain. Expression of procoagulant activity by these cells may provide evidence of macrophage activation and involvement in the initiation of lung fibrin deposition. An experimental model of hyperoxia-induced lung injury in rats was studied for assessment of the relationship of lung injury, fibrin deposition, and alveolar macrophage procoagulant activity. Lung injury was assessed histologically and functionally, and the accumulation of inflammatory cells was quantified by bronchoalveolar lavage. Pulmonary injury, manifested by increased capillary permeability, developed progressively during exposure to hyperoxia and was associated with significant augmentation of the procoagulant activity of alveolar macrophages early in the disease. This increase preceded the accumulation of polymorphonuclear leukocytes. Alveolar macrophage procoagulant activity had functional characteristics consistent with tissue factor. These studies provide evidence of early alveolar macrophage activation in acute hyperoxic lung injury in rats and suggest a role for procoagulant activity in the development of interstitial fibrin deposition.
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PMID:Alveolar macrophage procoagulant activity is increased in acute hyperoxic lung injury. 335 51

Corticosteroids affect type II alveolar epithelial cells, increase the lung's content of lipids associated with pulmonary surfactant, and have been used to treat the adult respiratory distress syndrome. We used hyperoxia to produce diffuse alveolar damage in rats and then determined the contents of lung lipids and the incorporation of precursors into these lipids while the rats recovered in air and received either hydrocortisone or saline injections. With saline injections (control) the total lipid content after hyperoxia and 48 hours recovery in air was nearly twice the lipid content of lungs never exposed to hyperoxia; many lipids, including phosphatidylcholine (PC), shared in this increase. With hydrocortisone injections the total lipid content, when expressed per lung, was not significantly greater than with saline injections but when expressed per mg DNA several lipid subgroups, including phosphatidylcholine, were significantly greater. Palmitate incorporation into most lipids of lung slices was not significantly different by 48 hours of recovery, and hydrocortisone had a modest effect after 96 hours. In contrast to the incorporation of palmitate, the incorporation of glycerol and of lysophosphatidylcholine (LPC) nearly doubled in most lipids during the recovery phase. Hydrocortisone injections were associated with greater glycerol incorporation after 96 hours of recovery in nearly all lipids and LPC incorporation was increased primarily into PC. We conclude that lung lipids increase markedly during recovery from severe oxygen toxicity and that hydrocortisone leads to additional increases of saturated and unsaturated PC.
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PMID:Lung phospholipids during recovery from oxygen toxicity are altered by hydrocortisone. 356 66

Healthy adult baboons exposed to 100% oxygen for 5 to 7 days maintained on continuous mechanical ventilation develop severe bilateral noncardiogenic pulmonary edema that resembles in many aspects the human adult respiratory distress syndrome (ARDS). In the present study, we evaluated the effects of hyperoxia for 5 to 6 days in 8 baboons to compare changes in abnormalities in bronchoalveolar lavage fluid (BALF) biochemical markers, hemodynamic measurements, and pulmonary function tests in order to find early predictors of lung injury. All animals had bilateral alveolar infiltrates, severe hypoxemia, and progressive deterioration of pulmonary function tests. Diffuse alveolar damage and mild-moderate pneumonias were found and were associated with low-grade bacterial infection. Total lung capacity, diffusing capacity for carbon monoxide, pulmonary static compliance, and oxygenation were significantly impaired after Day 5; BALF proteins, elastase, and total polymorphonuclear leukocytes increased significantly at least 24 h before (Day 4) any abnormalities in chest radiographs, pulmonary function tests, and hemodynamic measurements were detected. We conclude that exposure to 100% oxygen in this model causes marked gas exchange, hemodynamic, biochemical, cytologic, radiographic, and pathologic changes similar to those noted in patients with ARDS. Bronchoalveolar lavage abnormalities precede hemodynamic and gas exchange abnormalities.
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PMID:One hundred percent oxygen lung injury in adult baboons. 363 38

Alveolar fibrin deposition commonly occurs in the lungs of patients with the adult respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) from patients with ARDS, control patients with interstitial lung disease (ILD), congestive heart failure, or exposure to hyperoxia, and normal healthy subjects was studied to determine whether local alterations in procoagulant activity favor alveolar fibrin deposition in the lungs in ARDS. Procoagulant activity capable of shortening the recalcification time of plasma deficient in either factor VII or factor VIII was observed in unconcentrated BAL of all patients, but was significantly greater in BAL from patients with ARDS when compared with that of control subjects (p less than 0.001). Unconcentrated BAL from patients with ARDS shortened the recalcification time of plasma deficient in factor X, but no functional thrombin was detectable. BAL procoagulant from patients with ARDS was inhibited by concanavalin A, an inhibitor of tissue factor. The hydrolysis of purified human factor X by BAL from the ARDS and other patient groups was determined by measuring the amidolytic activity of generated factor Xa on its N-benzoyl-L-isoleucyl-L-glutamyl-glycyl-L-arginine-p-nitroanilide substrate. The procoagulant activity of BAL was associated with the development of amidolytic activity, indicating activation of factor X. BAL from patients with ARDS contained more factor X activating activity than did BAL from control groups (p less than 0.001). This activity was calcium dependent and was maximal at 1 mM ionized calcium. The BAL factor X activating activity was most active at neutral pH and was sedimented by ultracentrifugation at 100,000 x g.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with factor VII. 368 50

A major nonrespiratory function of the mammalian lung is that of a polymorphonuclear leukocyte reservoir. Within this reservoir, granulocytes are distributed between marginating and circulating pools. Under normal conditions these cells release little, if any, toxic metabolites. Situations which facilitate chemotactic release, activation of complement, or prolonged lowering of pulmonary blood flow lead to sequestration of large numbers of polymorphonuclear leukocytes in the lungs. If these polymorphonuclear leukocytes are then stimulated to release toxic oxygen species, proteases or other metabolites, existing defense mechanisms are overwhelmed and lung injury results. Anaphylatoxins generated by complement activation, humoral factors released from platelets or macrophages, and activation of the kallikrein-kinin and coagulation systems, may exacerbate damage to the alveolar-capillary membrane. Permeability of this membrane increases, there is interstitial and then alveolar edema, with subsequent pulmonary dysfunction. While there is little doubt that this scenario holds true for some experimental models of acute lung injury, its applicability to adult respiratory distress syndrome is still controversial. Nevertheless, adult respiratory distress syndrome does arise under conditions facilitating chemotactic factor release from macrophages (e.g. hyperoxia), in situations where widespread activation of complement occurs (e.g. sepsis, trauma, microemboli), and in shock conditions where pulmonary blood flow is often lowered. Correlations exist between adult respiratory distress syndrome and activation of complement, acute neutropenia, sequestration of polymorphonuclear leukocytes and enhanced functional and metabolic activity of granulocytes. Although these findings suggest that polymorphonuclear leukocytes are an important factor in the pathogenesis of adult respiratory distress syndrome, its precise role remains to be determined.
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PMID:The role of the polymorphonuclear leukocyte in the pathogenesis of the adult respiratory distress syndrome. 383 38


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