Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute hypoxemic respiratory failure (AHRF) can result from diverse lung insults. Toxic oxygen metabolites have been implicated in this clinical condition and in animal models of pulmonary edema. Hydrogen peroxide (H2O2), an oxygen metabolite, mediates tissue injury. We measured H2O2 levels by a spectrophotometric technique in the breath condensate of 68 mechanically ventilated patients; 13 patients with normal lungs undergoing elective surgery had no such detectable levels of H2O2. Fifty-five patients in the ICU meeting criteria for the adult respiratory distress syndrome (ARDS) had a higher concentration of H2O2 in the expired breath condensate than ICU patients without pulmonary infiltrates (2.34 +/- 1.15 vs 0.99 +/- 0.72 mumol/L, p less than 0.005). This marker had a sensitivity of 87.5 percent and a specificity of 81.3 percent in separating the two patient populations. Patients with AHRF and focal pulmonary infiltrates who did not meet criteria for ARDS also had higher concentrations of H2O2 (2.45 +/- 1.55 mumol/L) than patients without pulmonary infiltrates (p less than 0.001). No difference was observed between the expired H2O2 concentrations of patients with ARDS or patients with focal pulmonary infiltrates. Patients with brain injury or sepsis tended to have higher levels of H2O2 regardless of lung pathology. Increased levels of H2O2 are detected in the expired breath of ICU patients with focal lung infiltrates and in ARDS patients, which is consistent with the hypothesis that oxygen metabolites participate in the pathogenesis of ARDS and other forms of AHRF.
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PMID:Increased hydrogen peroxide in the expired breath of patients with acute hypoxemic respiratory failure. 276 20

Studies were conducted in isolated, buffer-perfused rat lungs to determine if prostaglandin (PG) E1 attenuated pulmonary edema provoked by hydrogen peroxide (H2O2). When lungs were challenged by 60 min of perfusion with H2O2 (generated by the reaction between glucose and glucose oxidase) the wet weight-to-dry weight ratio increased from control by 54%, indicating development of pulmonary edema. In contrast, lungs treated simultaneously with H2O2 plus PGE1 (1 microgram/min) failed to exhibit an elevated wet-to-dry weight ratio. H2O2-injured lungs demonstrated a modest 2 torr increase in pulmonary arterial perfusion pressure that was not influenced by simultaneous treatment with PGE1. Both radioimmunoassay (RIA) and high-performance liquid chromatographic (HPLC) analysis detected increased amounts of (5S)-5-hydroxy-6,8,11,14 eicosatetraenoic acid in the perfusion medium of H2O2-injured lungs (RIA, 48.0 +/- 14.7; HPLC, 54.8 +/- 13.5) relative to controls (RIA, 6.6 +/- 1.6; HPLC, 6.8 +/- 1.9), and simultaneous treatment with PGE1 tended to blunt this increase (RIA, 29.2 +/- 8.3; HPLC, 29.8 +/- 7.6). PGE1 abolished the increase in wet weight-to-dry weight ratio induced by exogenous leukotriene C4. Production of H2O2 by the glucose-glucose oxidase reaction was not influenced by PGE1. Taken together, these observations indicate that PGE1 attenuates H2O2-induced pulmonary edema formation in buffer-perfused rat lungs by mechanisms that may relate to inhibition of lung 5'-lipoxygenase activation and/or to inhibition of the injurious effects of endogenously produced lipoxygenase products.
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PMID:Salutary effects of prostaglandin E1 in perfused rat lungs injured with hydrogen peroxide. 303 98

Treatment with dimethylthiourea (DMTU), a potent O2 metabolite scavenger, prevented neutrophil-mediated acute edema in lungs of rabbits given phorbol myristate acetate (PMA) and in isolated rabbit lungs perfused with neutrophils and PMA. DMTU-treated rabbits given PMA did not increase their lung weight-to-total body weight ratios (5.0 +/- 0.3) or lung lavage albumin concentrations (14 +/- 4.6 mg/dl) in comparison to untreated rabbits given PMA (6.6 +/- 0.5 and 60 +/- 10 mg/dl, respectively). Similarly, DMTU-treated isolated rabbit lungs perfused with neutrophils and PMA did not gain weight (0 g) or increase their lavage albumin concentrations (82 +/- 17 mg/dl) in comparison to untreated lungs perfused with neutrophils and PMA (71 +/- 3.1 g and 1,299 +/- 47 mg/dl, respectively). DMTU did not appear to decrease edema by preventing increases in pulmonary arterial pressures (PAP). First, treatment with DMTU did not decrease initial PAP increases in rabbits given PMA. Second, even though addition of DMTU attenuated PAP increases in isolated lungs perfused with neutrophils and PMA, DMTU-treated isolated lungs did not develop acute edema when subjected to mechanical increases in venous outflow pressures. The mechanism by which DMTU decreases lung edema is unclear but may involve scavenging of toxic O2 metabolites, since DMTU also decreased hydrogen peroxide (H2O2) and hydroxyl radical (OH) concentrations in in vitro mixtures containing neutrophils and PMA.
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PMID:Dimethylthiourea decreases acute lung edema in phorbol myristate acetate-treated rabbits. 309 13

Re-expansion pulmonary edema (RPE) has been attributed to decreased lung interstitial pressures from a variety of mechanisms. Because some recent studies have implicated mechanisms that increase microvascular permeability in RPE, we tested whether the edema were due to free radical generation during re-expansion and reoxygenation of the collapsed lung. We used a rabbit model of RPE to test the effects of intracellular (dimethylthiourea) or extracellular (catalase) oxygen metabolite scavengers. Allopurinol was administered separately to determine whether xanthine oxidase was an important source of superoxide in this model. Edema was quantitated both gravimetrically and histologically, and lung xanthine oxidase activity was measured using a sensitive fluorometric assay with pterin as substrate. The results suggest indirectly that OH. or H2O2 (derived from O2-) contribute to the well-documented increase in lung permeability in RPE because dimethylthiourea, dimethylthiourea plus catalase, or catalase alone inhibited the edema to various degrees. Further, we observed histologically that increased numbers of neutrophils were present in re-expanded lungs and that neutrophil infiltration appeared to be diminished by antioxidant administration. Allopurinol did not decrease the edema, because xanthine oxidase activity in rabbit lung tissue is extremely low. We speculate that free radical generation in lung tissue contributes to the pathogenesis of RPE, although reinitiation of lung perfusion and ventilation requires a rapid change in intrathoracic pressure.
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PMID:Re-expansion pulmonary edema. A potential role for free radicals in its pathogenesis. 314 79

Because reactive O2 metabolites have been demonstrated to be potent mediators of vascular dysfunction and are synthesized by lung tissue, their involvement as mediators of oleic acid (OA)-induced pulmonary edema in the isolated Krebs-perfused rabbit lung was assessed. Injection of OA (0.1 ml) into the pulmonary artery after vehicle pretreatment induced marked increases in lung weight [50.4 +/- 13.9 vs. 4.2 +/- 2.0 (SE) g 45 min after OA or vehicle, respectively, P less than 0.05], an index of pulmonary edema, and airway pressure. OA also caused a significant though minimal increase in pulmonary arterial pressure. Pretreatment with catalase (1,000 U/ml), a scavenger of H2O2, significantly (P less than 0.05, Friedman's) attenuated the increases in lung weight (50.4 +/- 13.9 vs. 15.1 +/- 4.9 g), airway pressure, and pulmonary arterial pressure. In contrast to catalase, pretreatment with Cu-tryptophan (40 microM), a lipid-soluble scavenger of superoxide, provided no protective effect by itself, nor was there any potentiation of protection when combined with catalase. Further evidence implicating O2 metabolites in OA-induced edema was obtained by electron paramagnetic resonance (EPR) spectroscopy of perfusate samples to which the spin trap, sodium 3,5-dibromo-4-nitrosobenzenesulfonate (10 mM), was added. Analysis of these samples revealed the presence of free radicals after OA. Pretreatment with catalase (1,000 U/ml) and superoxide dismutase (250 U/ml) attenuated the EPR signal, indicating that proximal formation of O2 free radicals was in part responsible for the signal. These results suggest that reactive O2 metabolites are mediators of OA-induced pulmonary edema in the isolated perfused rabbit lung.
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PMID:Catalase pretreatment attenuates oleic acid-induced edema in isolated rabbit lung. 318

Neutrophils have been implicated in the pathogenesis of acute lung injury associated with clinical and experimental sepsis. Data from in vitro systems and experimental animals have suggested that neutrophil-derived oxidants, particularly H2O2, may be primarily responsible for endothelial damage, vasoconstriction, and lung edema. With the use of endotoxin infusion as an in vivo model of sepsis we tested the hypothesis that pretreatment with catalase, a peroxide scavenger, would ameliorate the resultant changes in pulmonary vasoconstriction and lung fluid balance. Paired experiments were performed in 16 goats with chronic lung lymph fistulas. One group of animals (n = 7) received endotoxin first alone and then again, several days later, after pretreatment with Ficoll-linked catalase. As a control, identical experiments were performed in a separate group (n = 6) with Ficoll-linked albumin substituted for Ficoll-catalase. A third group (n = 3) was given endotoxin alone and then again during a continuous infusion of catalase. Plasma and lymph levels of catalase were comparable to or exceeded those previously shown to be completely protective in isolated perfused lung preparations and in vitro systems. Endotoxin caused neutropenia, pulmonary arterial hypertension, decreased cardiac output, and increases in lymph flow to approximately three times base line, with a return of all variables toward control values by 6 h. Catalase pretreatment produced no significant differences in any of these variables. These experiments do not support a role for H2O2 as a mediator of acute lung injury due to endotoxemia.
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PMID:Effect of intravenous catalase on the pulmonary vascular response to endotoxemia in goats. 328 99

Toxic, partially reduced metabolites of oxygen (toxic oxygen radicals) are increasingly implicated in acute leukocyte-mediated tissue injury. To further probe the roles of oxygen radicals in acute lung edema, I studied the effects of a recently described and very potent oxygen radical scavenger, dimethylthiourea (DMTU) (Fox, R. B., R. N. Harada, R. M. Tate, and J. E. Repine, 1983, J. Appl. Physiol., 55:1456-1459) on polymorphonuclear leukocyte (PMN) oxidant function and on two types of lung injury mediated by oxygen radicals and PMN. DMTU (10 mM) blocked 79% of hydroxyl radical (OH) production by PMN in vitro without interfering with other PMN functions, such as O-2 production, myeloperoxidase activity, chemotaxis, degranulation, or aggregation. When isolated rat lung preparations were perfused with PMN activated to produce OH, lung weights were increased from 2.3 +/- 0.2 to 11.2 +/- 0.8 g. DMTU (10 mM) prevented 70% of these increases (lung weights, 5.0 +/- 1.1 g, P less than 0.005). Finally, when intact rats were exposed to 100% O2 for 66 h, lung weight:body weight ratios were increased from 5.78 +/- 0.33 to 8.87 +/- 0.16 g. DMTU (500 mg/kg) prevented 83% of this hyperoxia-induced lung edema in vivo (lung:body weight ratios, 6.05 +/- 0.21, P less than 0.001). Pharmacokinetic studies showed that DMTU diffused effectively into lung interstitial fluids and had a relatively long half-life (25-35 h) in the circulation. Because a variety of oxygen radicals, such as superoxide (O-2), hydrogen peroxide (H2O2), or OH are produced by PMN, there is usually some uncertainty about which one is responsible for injury. However, in these studies, DMTU did not scavenge O-2 and scavenged H2O2 only very slowly while scavenging OH very effectively. Therefore, DMTU may be useful in the investigation of the roles of oxygen radicals, especially OH, in acute granulocyte-mediated tissue injury.
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PMID:Prevention of granulocyte-mediated oxidant lung injury in rats by a hydroxyl radical scavenger, dimethylthiourea. 609 May 4

In this study, we have shown that chickens, frogs, and toads are resistant to acute pulmonary injury by a variety of toxic agents, (O2, hyperbaric O2, paraquat, and silica), that cause extensive acute injury in mammals. Acute pulmonary injury is defined as a massive influx of inflammatory cells, both interstitially and into the alveolar spaces, pulmonary edema, hemorrhage, and the presence of H2O2 and O-2 in the lavaged supernatant, occurring within 48 h. In some cases, chronic effects of the toxins were observed after 90 h., i.e., hemorrhage, fibrosis, and an accumulation of interstitial inflammatory cells. In all three nonmammal systems, isolated inflammatory cells failed to respond chemotactically in vitro to known mammalian chemotaxins. Pulmonary lavage of the exposed chickens, frogs, and toads also failed to produce inflammatory cells. Pulmonary edema was not detected in any of the animals by comparison of lung weight to total body weight. Intratracheal injections of silica for 2 weeks did produce chronic effects in chickens and frogs. Morphologically, the lungs showed signs of fibrosis and accumulation of interstitial inflammatory cells, but no intraalveolar cells. After 90 h of hyperbaric O2, frogs exhibited a massive infiltration of interstitial inflammatory cells and hemorrhage. Elevated O2 levels (100%) for 2 weeks under normal atmospheric conditions produced no changes in frog lungs or in the amount of inflammatory cells in the lungs. Intravenous injections of paraquat for up to 208 h failed to initiate an accumulation of pulmonary inflammatory cells or the development of pulmonary edema in chickens. There was also no detectable H2O2 or O-2 in the lavaged supernatant. It was not determined whether paraquat had a longer or more chronic effect on chickens. We suggest that the lack of an acute pulmonary inflammatory mechanism in chickens, frogs, and toads is in part responsible for the resistance of these animals to acute pulmonary injury by oxidizing mammalian toxins.
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PMID:Characterization of pulmonary cellular influx differentials to known toxic agents between species. 629 9

This article is a review of the current literature concerning the possible involvement of oxygen radicals in the development of pulmonary edema. The article focuses on changes in capillary endothelium caused by many different imposed experimental conditions that may be related to the generation of O2, OH. or H2O2. Data from our laboratory show that scavengers such as superoxide dismutase, dimethylsulfoxide, and catalase as well as leukocyte depletion provide partial protection to the very caustic alpha-naphthylthiourea. The literature concerning the possible involvement of leukocyte or tissue generation of oxygen radicals in the various forms of pulmonary edema is combined into a simple model that may explain why pathologic tissues show variable responses to compounds that should either scavenge the oxygen radicals or prevent leukocyte involvement.
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PMID:The effects of oxygen radicals on pulmonary edema formation. 641 81

The fractionation of Phoneutria nigriventer spider venom by gel filtration (Sephadex G-10-120) followed by ion-exchange chromatography (microgranular CM-cellulose-52) resulted in sixteen fractions (CI to CXVI) from which CVII+VIII, CIX and CX+XI caused dose-dependent and short-lived contractions of both arterial and venous rabbit vessels. Fraction CX+XI was further purified by a reverse phase HPLC, and a contractile polypeptide (PNV2) was isolated. The amino terminal sequence of PNV2 (LAKRADICQPGKTSQRACET) indicated that it represents a pure polypeptide consisting of a single chain. Furthermore, the amino acid analysis of PNV2 revealed the presence of four disulfide bridges, a high content in Lys (14%), Glx (11%), and the absence of His. The global amino acid composition showed that this polypeptide is composed of 102 residues (Trp not included) with a calculated molecular weight of 12,114. Whether this peptide is responsible for the vascular alterations observed in Phoneutria envenomation, such as lung edema and priapism, remains to be further investigated.
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PMID:Identification of a new vascular smooth muscle contracting polypeptide in Phoneutria nigriventer spider venom. 821 54


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