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)

Tracheal insufflation of tumor necrosis factor (TNF; 5 micrograms or 1.2 x 10(5) U) markedly enhanced the survival of adult rats exposed to 100% O2: 12 of 17 rats (71%) survived for greater than 11 days, whereas 30 of 30 control (Hanks' balanced salt solution) insufflated rats (100%) died within 3 days of O2 exposure. Insufflation of gamma-interferon (5 micrograms) or intraperitoneal injection of up to 40 micrograms TNF did not afford any protection. At 55 h after O2 exposure, TNF-insufflated rats showed less pulmonary edema, as determined by the extravascular lung water content-to-bloodless lung dry weigh ratio and less alveolar capillary leak as determined by the protein content in the bronchoalveolar lavage fluid, than control insufflated rats similarly exposed. This protection against O2 toxicity by TNF insufflation was associated with increased lung superoxide dismutase, catalase, and glutathione peroxidase activities. The enhancement of lung antioxidant enzyme activities was noted at 55 h of O2 exposure, when control animals began to die of O2 toxicity. This temporal relationship suggests that TNF-induced increase in antioxidant enzyme activities contributes, at least in part, to the observed protection.
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PMID:Tracheal insufflation of tumor necrosis factor protects rats against oxygen toxicity. 234 45

This study evaluated the effects of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) in re-expansion pulmonary edema, a unilateral lung injury due in part to re-oxygenation of hypoxic, collapsed lung tissue. The hypothesis underlying this investigation was that extracellular superoxide contributed to the lung inflammation in this model, and that PEG-SOD could be used to test for extra-cellular superoxide involvement. The right lungs of 2-3 kg rabbits were collapsed for seven days by intrapleural air injections. Immediately prior to lung re-expansion, rabbits received intravenously 10,000 units/kg PEG-SOD (n = 6) or an equal volume of H2O2-inactivated PEG-SOD (n = 6). Inactive PEG-SOD pretreated rabbits had a marked increase in re-expanded lungs' lavage albumin concentration (right 1653 +/- 230 micrograms/ml, left 404 +/- 160 micrograms/ml; p less than .01). Active PEG-SOD did not inhibit this permeability increase (right 1744 +/- 242 micrograms/ml, left 180 +/- 53 micrograms/ml; p less than .01). However, active PEG-SOD significantly decreased both total number and percent neutrophils in alveolar lavage (right 24.8 +/- 9.4%, left 4.2 +/- 0.8%; p less than .05) compared to inactive PEG-SOD pretreated rabbits (right 52.8 +/- 5.8%, left 8.7 +/- 2.4%; p less than .01). Pretreatment with active PEG-SOD significantly increased lung tissue (20.4 +/- 1.5 units/mg DNA), blood (400 +/- 8 units/ml) and right lung lavage (30.0 +/- 3.1 units/ml) SOD activities compared to those from inactive PEG-SOD pretreated rabbits (respectively: 16.0 +/- 1.0 units/mg DNA, 335 +/- 14 units/ml and 10.8 +/- 1.3 units/ml; p less than .05 for each comparison).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polyethylene glycol-conjugated superoxide dismutase in unilateral lung injury due to re-expansion (re-oxygenation). 237 17

Amiodarone (ADR), a new antiarrhythmic drug for life-threatening cardiac arrhythmias, causes pneumonitis or lung fibrosis in a sizeable minority of patients. The cause of lung damage is not known. We have shown that infusion of 10 mg amiodarone into the inflow circuit of ventilated and perfused rabbit lungs causes immediate increase in pulmonary artery pressure (mean +/- SEM) (from 13.6 +/- 1.2 to 40.6 +/- 9.5 mm Hg, p less than 0.01) and pulmonary edema with marked increase in the pulmonary generation of thromboxane and leukotrienes C4 and/or D4. Albumin (2 g%) in the perfusate prevents any increase in lung perfusion pressure or edema formation. When lung perfusion pressure increase is blocked with the combined cyclooxygenase and lipoxygenase inhibitor enolicam sodium (CG5391B, 35 microM in perfusate), significant lung edema still occurs after amiodarone, indicating that amiodarone causes increased alveolar-capillary membrane permeability. Addition of catalase (100 U/ml) or superoxide dismutase and catalase (100 U/ml each) to perfusate fails to protect from amiodarone lung injury. Immediate infusion of amiodarone (10 mg) into lungs ventilated with room air (ADR + RA) causes an increase in lung weight gain from baseline (delta W) of 5.7 +/- 1.5 g/min. Compared with ADR + RA, ventilation of lungs with 4% O2 (delta W = 0.7 +/- 0.3 g/min, p less than 0.05), pretreatment of rabbits for 3 days with butylated hydroxyanisole (BHA, 100 mg/kg/day i.p., delta W = 0.05 +/- 0.02 g/min, p less than 0.01), pretreatment of rabbits for 3 days with vitamin E (Vit E, 300 U/day orally, delta W = 0.6 +/- 0.2 g/min, p less than 0.05), or addition of N-acetylcysteine to the lung perfusate (NAC, 5 mM, delta W = 0.1 +/- 0.08 g/min, p less than 0.01) all protect from lung edema formation after amiodarone. Amiodarone (100 mg) also caused a marked increase in luminol-enhanced lung chemiluminescence, lung production of superoxide anion (O2-), and tissue levels of lung glutathione disulfide. These results suggest that amiodarone causes lung injury by an oxidant mechanism.
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PMID:Amiodarone causes acute oxidant lung injury in ventilated and perfused rabbit lungs. 245 31

We have developed a model of reperfusion injury in Krebs buffer-perfused rabbit lungs, characterized by pulmonary vasoconstriction, microvascular injury, and marked lung edema formation. During reperfusion there was a threefold increase in lung superoxide anion (O2-) production, as measured by in vivo reduction of nitroblue tetrazolium, and a twofold increase in the release of O2- into lung perfusate, as measured by reduction of succinylated ferricytochrome c. Injury could be prevented by the xanthine oxidase inhibitor allopurinol, the O2- scavenger SOD, the hydrogen peroxide scavenger catalase, the iron chelator deferoxamine, or the thiols dimethylthiourea or N-acetylcysteine. The protective effect of SOD could be abolished by the anion channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid, indicating that SOD consumes O2- in the extracellular medium, thereby creating a concentration gradient favorable for rapid diffusion of O2- out of cells. Our results extend information about the mechanisms of reperfusion lung injury that have been assembled by studies in other organs, and offer potential strategies for improved organ preservation, for treatment of reperfusion injury after pulmonary thromboembolectomy, and for explanation and therapy of many complications of pulmonary embolism.
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PMID:Role of reactive oxygen species in reperfusion injury of the rabbit lung. 246 23

The reimplantation response after lung transplantation may critically impair the function of transplanted lungs in the early postoperative period. The purpose of this study is to evaluate the factors which cause this reimplantation response. Using canine left lungs, four groups were studied. Group I underwent complete hilar stripping (n = 6). Group II underwent complete hilar stripping and kept in warm ischemia for 60 min. by clamping left pulmonary artery and veins (n = 6). Group III underwent the same surgery as Group II and administered superoxide dismutase (SOD) (12000 U/kg/h) during reperfusion (n = 7). Group IV underwent autotransplantation of left lung (n = 6). To evaluate the function of left lung, arterial blood gas, pulmonary arterial pressure, aortic pressure, cardiac output and left extravascular lung water (liter EVLW) were measured in a transient contralateral pulmonary arterial occlusion before operation and 60 min. after reventilation and reperfusion. The measurement of EVLW was performed by thermal-green dye double indicator dilution method. The results obtained were as follows. 1) The values of liter EVLW measured in rt. pulmonary arterial occlusion were extremely well correlated with those of both lung EVLW. (r = 0.943 p less than 0.001). 2) The ratios of postoperative-liter EVLW: preoperative-liter EVLW and postoperative-total pulmonary resistance (TPR): preoperative-TPR were as follows: Group I; 1.29 +/- 0.19 and 1.23 +/- 0.36, Group II; 1.85 +/- 0.49 and 1.69 +/- 0.36, Group III; 1.28 +/- 0.17 and 1.50 +/- 0.36 Group IV; 2.28 +/- 0.40 and 1.70 +/- 0.34. These data indicate that the most important factor of reimplantation response at the time of this acute phase is the oxygen free radical-induced reperfusion injury. Hilar stripping, ischemic injury and surgical trauma are also important factors of reimplantation response. Vascular anastomosis is not so important when it is done well technically. 3) Administration of SOD provides protection against lung edema after lung transplantation.
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PMID:[Experimental studies on reimplantation response after lung transplantation]. 250 45

We examined the basis of reperfusion-induced pulmonary edema produced by pulmonary artery occlusion and subsequent reperfusion. After a 24-h period of occlusion of a rabbit pulmonary artery followed by a 2-h period of reperfusion, the lungs were removed from the animal and perfused with a 0.5 g% Ringer's-albumin solution. An increase in lung weight was observed within 60 min compared with control lungs (i.e., lungs subjected to pulmonary arterial occlusion but not reperfusion) (p less than 0.05). Shorter periods of occlusion (6 or 12 h) did not result in edema, which suggests that a period of ischemia was required for the reperfusion-induced pulmonary edema. The extravascular lung water content also increased in the contralateral lung (i.e., the lung not subjected to pulmonary arterial occlusion and reperfusion). The capillary filtration coefficient increased in reperfused lungs compared with controls (p less than 0.05), indicating an increase in lung vascular permeability following reperfusion. Infusion of allopurinol (a xanthine oxidase inhibitor) and superoxide dismutase during the reperfusion period prevented the increases in lung weight and vascular permeability; infusion of catalase was ineffective. We conclude that pulmonary reperfusion following pulmonary artery occlusion increases pulmonary vascular permeability, which is mediated by the generation of oxidants.
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PMID:Pulmonary edema after pulmonary artery occlusion and reperfusion. 281 6

En bloc transplantation of the heart and lungs was performed in 15 chacma baboons; the donor organs were stored between 4 and 6 hours before transplantation. The hearts were perfused in the donor animals with 15 ml/kg Wicomb's cardioplegic solution at 4 degrees C, the lungs with either 20 ml/kg 4 degrees C Collins' solution with an added 2.5% dextrose and 12 mEq magnesium sulfate (Collins' solution, group 1, n = 8), Collins' solution plus superoxide dismutase (40,000 U/L superoxide dismutase, group 2, n = 4), or Collins' solution plus superoxide dismutase plus peroxidase (5000 U/L peroxidase plus mannitol, group 3, n = 3). The pulmonary artery perfusion pressure was not allowed to exceed 50 cm water; the lungs were maintained at 30% to 50% inflation, and external cooling was applied. After explantation the thoracic organs were stored in 0.9% saline solution at 4 degrees C. In groups 1 (Collins' solution) and 2 (Collins' plus superoxide dismutase) all surviving baboons revealed normal blood gas values and normal light and electron microscopic histology at 24 hours. Three animals had further biopsies at intervals between 1 and 9 days, at which time the histology of the lungs proved normal and well preserved. All three baboons in group 3 (Collins' plus superoxide dismutase plus peroxidase) had grossly abnormal blood gas values from the time of operation, and all died within 9 hours; light microscopy of the lungs showed early lung infarctlike lesions and in one case pulmonary edema. These preclinical findings proved that storage of the lungs in Collins' solution with or without superoxide dismutase is possible for up to 5 hours; the addition of peroxidase had a detrimental effect.
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PMID:Successful orthotopic heart-lung transplantation in the baboon after five hours of cold ischemia with cardioplegia and Collins' solution. 311 42

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

In order to establish an animal model for assessing early and sensitive biochemical indicators of pulmonary damage, we studied the effects of inhaled CdCl2 (5 mg/m3.h; mass median aerodynamic diameter (MMAD) = 1.4 microns; SDg = 1.8) on the antioxidant defense and pulmonary surfactant systems of rat lungs. Rats were sacrificed 1, 4, 8, and 16 d after inhalation. Pulmonary edema (wet/dry weight) was observed on d 1. The total activities of the enzymes superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G6PD) in the lung homogenates of the treated animals were significantly throughout the 16-d period. Glutathione reductase (GR) was increased on d 4 and after. The general increases of SOD, GR, and the lysosomal enzymes acid phosphatase and beta-N-acetylglucosaminidase could be attributed to changes in the cellularity of the lung tissue. The significant increase in the specific activity of G6PD on d 4 suggested enzyme stimulation. Concurrently, the response of the surfactant system was measured by assaying the alkaline phosphatase (AKP) and the phospholipid content in the homogenates and in the cell-free bronchoalveolar lavage (BAL) fluids. The AKP activity in the homogenates decreased by 30%, while no activity was detected in the BAL on d 1, suggesting an inhibition of AKP by Cd. The secretion of surfactant seemed altered at this early time: phospholipid in the BAL decreased by 44%, although it increased by 61% in the tissue. The high recovery of phospholipid (312%) in the BAL on d 4 and the important changes in the AKP activity in the BAL from d 4 to 16 may reflect alterations in the processing of the surfactant. The effect of Cd on AKP makes this enzyme a potential marker of the metal redistribution in the pulmonary alveolar region, which could be a useful tool in long-term studies.
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PMID:Toxicity of inhaled cadmium chloride: early responses of the antioxidant and surfactant systems in rat lungs. 334 99

The effects of the cytochrome P450 inducer beta-naphthoflavone (BNF) on NO2 toxicity were studied in two strains of mice. In one strain (C57B1/6J), cytochrome P450 could be induced by the aromatic hydrocarbon, while in the other strain (DBA/2J) cytochrome P450 was not inducible by this compound. Mice were treated with BNF before and during 4 days of exposure to 20 ppm NO2. The body growth of NO2-exposed mice improved only in BNF-treated C57B1/6J mice. In this strain, BNF reduced both pulmonary edema (as measured by wet and dry lung weights or as assessed by histological studies) and lung peroxidation (as measured by malondialdehyde). This protective effect of BNF on NO2 toxicity in C57B1/6J mice was associated with an increase in the components of the cytochrome P450 system (cytochrome P450 and cytochrome b5), whereas the activities of pulmonary antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and glutathione reductase) were not significantly increased. These data suggest that the induction of the cytochrome P450 system may be important in promoting NO2 tolerance in those strains of mice in which the cytochrome P450 system is genetically inducible.
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PMID:Protective effect of beta-naphthoflavone against NO2 toxicity in mice with genetically inducible lung cytochrome P450. 335 60


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