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)

Tumor necrosis factor alpha (TNF-alpha) activity, platelet and neutrophil degranulation and margination, and increased vascular permeability are central to the pathophysiology of endotoxin-mediated acute lung injury. Nonanticoagulant activities of low molecular weight heparin (LMWH) include solubilization of the TNF-alpha receptor protein, inhibition of neutrophil adhesion, and regulation of thromboxane B2 (TXB2) biosynthesis. In this study, we evaluated the ability of LMWH to modulate TNF-alpha and TXB2 activity during endotoxemia and the subsequent effects on pulmonary hemodynamics. Domestic pigs 8-10 weeks old were anesthetized and catheterized for standard cardiopulmonary measurements and the lungs harvested for cuff:vessel ratio, myeloperoxidase activity, and permeability index. Pigs were randomly assigned to one of four groups: lipopolysaccharide (LPS) (n = 6), given .5 microg/kg/h Escherichia coli LPS intravenously for 6 h; saline control (n = 5); LMWH (n = 5), given .5 mg/kg LMWH for 30 min, followed by .5 mg/kg/h; and LMWH + LPS (same dosages, n = 6). Administration of LPS resulted in increased plasma TNF-alpha and TXB2 activity; increased pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen tension; decreased systemic arterial oxygen tension; and pulmonary edema. The cardiopulmonary parameters for the LMWH-treated pigs did not differ from those of the saline-treated control pigs. Pretreatment with LMWH attenuated the LPS-mediated TNF-alpha and TXB2 activity and attenuated LPS-mediated pulmonary hypertension, hypoxemia and neutrophil emigration, and edema formation. In conclusion, the data show that the protective effects of LMWH in this model of acute lung injury are associated with altered neutrophil adhesion and TNF-alpha and thromboxane activity.
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PMID:Low molecular weight heparin prevents the pulmonary hemodynamic and pathomorphologic effects of endotoxin in a porcine acute lung injury model. 956 56

Postpneumonectomy pulmonary oedema (PPO) complicates a significant number of thoracic surgical procedures involving lung resection and in its extreme form is indistinguishable from the acute respiratory distress syndrome. This study investigated the possibility that ischaemia-reperfusion (I-R) injury contributes to PPO via the production of damaging reactive oxygen species. In a prospective, observational, comparative study, patients undergoing pneumonectomy, lobectomy, or wedge resection or open lung biopsy were investigated for perioperative changes in lung function indicative of lung injury and changes in plasma indices of oxidative damage. Significant percentage perioperative falls in plasma protein thiol levels (-17.9+/-7.0% for pneumonectomy, -24.3+/-5.5% for two-lobe lobectomy and -10.2+/-2.2% for one-lobe lobectomy, p<0.05) and rises in plasma protein carbonyl levels (26.2+/-10.5% for pneumonectomy, p<0.05, 9.8+/-7.0% for two-lobe lobectomy and 5.0+/-2.7% for one-lobe lobectomy) were identified, but not in patients undergoing biopsy or wedge resection. Plasma myeloperoxidase levels rose in all groups, but not significantly. The carbon monoxide transfer coefficient (K(CO)) fell significantly in patients undergoing lobectomy (p<0.05) but not in those undergoing wedge resection, lung biopsy or pneumonectomy. Changes in markers of oxidative protein damage occurred in patients undergoing lung resection, although the gas transfer coefficient fell significantly only following lobectomy. Oxidative damage occurs during pulmonary resection, although associated effects on gas exchange are seen only after lobectomy.
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PMID:Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection. 964 51

The effect of a selective leukocyte elastase inhibitor, ICI 200,355, on thrombin-induced pulmonary oedema was studied in rats. Thrombin administration produced an increase in lung weight (P < 0.05), wet weight/ dry weight ratio (P < 0.05), and relative lung water content (P < 0.05). The lung weight increase was reduced by the elastase inhibitor in doses of 2000, 200 and 20 micrograms/kg per h (P < 0.05), but not by 2 micrograms/kg per h. A dose of 20 micrograms/ kg per h seems to be optimal, since 10-fold and 100-fold increases in dose did not further improve the effect. Free elastase activity in lung tissue was higher after thrombin infusion than in controls, but was not depleted by the elastase inhibitor in vivo (P < 0.05). This elastase activity in the lung was, however, inhibited by the elastase inhibitor in vitro, indicating that the inhibitor can block extracellular, but not intracellular elastase activity. Thrombin infusion resulted in a significant decrease in plasma elastase inhibitory capacity (P < 0.05), which was depleted by the elastase inhibitor (20 micrograms/kg per h) (P < 0.05). Myeloperoxidase activity was significantly increased in lung tissue after thrombin infusion (P < 0.05). Lung myeloperoxidase activity 5 min after thrombin infusion was not affected by the elastase inhibitor, but the inhibitor induced a further increase in myeloperoxidase as seen 90 min after thrombin infusion, indicating that the effect of this inhibitor on pulmonary oedema is not due to reduction of leukocyte infiltration in the lungs, but may partly be exerted by prevention of neutrophil destruction.
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PMID:A leukocyte elastase inhibitor reduces thrombin-induced pulmonary oedema in the rat: mechanisms of action. 1010 47

Cardiotrophin-1 (CT-1) is a recently discovered member of the gp130 cytokine family, which includes IL-6, IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Recent evidence suggests that, like other members of this family, CT-1 may possess anti-inflammatory properties. We hypothesized that in vivo CT-1 administration would attenuate endotoxin (ETX)-induced acute lung injury. We studied the effects of CT-1 (100 microgram/kg ip, 10 min prior to ETX) in a rat model of ETX-induced acute lung injury (Salmonella typhimurium lipopolysaccharide, 20 mg/kg ip). Six hours after ETX, lungs were harvested for determination of neutrophil accumulation (myeloperoxidase, MPO, assay) and lung edema (wet-to-dry weight ratio). Mechanisms of pulmonary vasorelaxation were examined in isolated pulmonary artery rings at 6 h by interrogating endothelium-dependent (response to acetylcholine) and endothelium-independent (response to sodium nitroprusside) relaxation following alpha-adrenergic (phenylephrine)-stimulated preconstriction. CT-1 abrogated the endotoxin-induced lung neutrophil accumulation: 2.3 +/- 0.2 units MPO/g wet lung (gwl) vs 6. 3 +/- 0.3 units MPO/gwl in the ETX group (P < 0.05 vs ETX, P > 0.05 vs control). Similarly, CT-1 prevented ETX-induced lung edema: wet-to-dry-weight ratio, 4.473 +/- 0.039 vs 4.747 +/- 0.039 in the ETX group (P < 0.05 vs ETX, P > 0.05 vs control). Endotoxin caused significant impairment of both endothelium-dependent and -independent pulmonary vasorelaxation, and CT-1 attenuated this injury. Thus, cardiotrophin-1 possesses significant anti-inflammatory properties in a model of endotoxin-induced acute lung injury.
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PMID:Cardiotrophin-1 attenuates endotoxin-induced acute lung injury. 1035 26

Nitric oxide (NO) may either protect against or contribute to inflammatory lung injury. In this study we investigated whether inhalation of 20 ppm NO alters tyrosine nitration, and we assessed the degree of lung inflammation and edema in rats after lipopolysaccharide (LPS) instillation. The amount of nitrotyrosine relative to the total amount of tyrosine was measured in lung homogenates, and lung tissue sections were stained for nitrotyrosine and aminotyrosine (a reduced form of nitrotyrosine). Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, and myeloperoxidase activity was measured in lung homogenate. Lung edema and inflammatory cell accumulation in lung tissue were estimated by extravascular lung water weight (EVLW) and extravascular dry lung weight (EVDW), respectively. LPS instillation caused increases in nitrotyrosine concentration and immunohistochemical staining of nitrotyrosine and aminotyrosine in the lungs. LPS instillation increased the BALF leukocyte count, myeloperoxidase activity in lung tissue, and both EVLW and EVDW. Inhalational exposure to 20 ppm NO induced nitrotyrosine and aminotyrosine formation only in bronchial epithelial cell surface of the lungs not instilled with LPS. NO inhalation reduced the increases in nitrotyrosine and aminotyrosine in LPS-instilled lung tissue as well as the leukocyte count in BALF and myeloperoxidase activity in lung tissue, but it did not significantly change EVLW or EVDW. Leukocyte depletion in LPS-instilled rats reduced interstitial inflammatory cells, which were stained with nitrotyrosine and aminotyrosine, and attenuated the nitrotyrosine staining of alveolar capillaries. These results suggest that inhalation of 20 ppm NO reduces leukocyte accumulation in the lungs and inhibits tyrosine nitration caused by LPS instillation.
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PMID:Inhaled nitric oxide reduces tyrosine nitration after lipopolysaccharide instillation into lungs of rats. 1043 Jul 46

Inflammatory reactions are associated with sequestration of leukocytes in the lung. Complement activation leads to accumulation of leukocytes in alveolar septa and alveoli, to lung edema and hemorrhage. Although in organs other than the lung leukocytes interact with the vascular endothelium only in postcapillary venules, alveolar capillaries are considered to be the site of leukocyte sequestration in the lung. However, pulmonary venules and arterioles have not been investigated systematically after complement activation so far. A closed thoracic window was implanted in anesthetized rabbits; leukocytes and red blood cells were stained, and the movement of these cells was measured in superficial pulmonary arterioles, venules and alveolar capillaries using fluorescence video microscopy before and 30 and 60 min after infusion of cobra venom factor (CVF). Erythrocyte velocity and macrohemodynamic conditions did not change after CVF infusion and were not different from the sham-treated controls. The number of sticking leukocytes increased significantly compared to baseline and control: by 150% in arterioles and in venules and by 740% in alveolar capillaries within 60 min after CVF infusion. The width of alveolar septa in vivo was significantly enlarged after CVF infusion, indicating interstitial pulmonary edema. At the end of the experiments, myeloperoxidase activity was higher in the CVF group, showing leukocyte sequestration in the whole organ. It is concluded that complement activation by CVF induces leukocyte sequestration in lung arterioles, venules and alveolar capillaries and leads to mild lung injury.
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PMID:Leukocyte sequestration in pulmonary microvessels and lung injury following systemic complement activation in rabbits. 1047 42

Prevention of ischemia-reperfusion (IR) injury is crucial for successful lung transplantation. We investigated whether a nitric oxide donor, nitroglycerin (NTG), could suppress the oxidative stress of IR injury and improve pulmonary function after reperfusion in an ex vivo rat lung perfusion model. In Fresh group of animals, the lungs were flushed with perfusate, followed immediately by reperfusion, and no lung injury was observed. In NTG- and NTG+ groups of animals, the lungs were flushed with perfusate alone or perfusate containing NTG, respectively. Harvested lung and heart blocks from these latter two groups were immersed in the corresponding perfusate at 4 degrees C for 15 h, and were then reperfused for 60 min. Reperfusion induced pulmonary edema in the NTG- group, but not in the NTG+ group. Shunt fractions in NTG+ group were significantly lower than in the NTG- group throughout reperfusion. NTG had no effect on pulmonary arterial pressure or myeloperoxidase activity. In contrast, oxidative DNA damage assessed immunohistochemically with a monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly increased in the NTG- group, in the order alveolar epithelium > pulmonary endothelium > bronchial epithelium. NTG treatment significantly decreased staining with the anti-8-OHdG antibody in all three areas of tissue. Therefore, administration of NTG attenuates the oxidative stress of IR injury, and may improve pulmonary function after reperfusion.
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PMID:Cytoprotective effects of nitroglycerin in ischemia-reperfusion-induced lung injury. 1071 46

Lung injury is a major cause of patient morbidity in acute pancreatitis. The purpose of this study was to examine the mechanism of pulmonary infiltration and lung injury in acute pancreatitis. Mice were fed a choline-deficient/ethionine-supplemented (CDE) diet for 144 hours to induce severe acute pancreatitis. Serum samples were collected for measurement of biochemical markers of disease and for the detection of tumor necrosis factor-alpha (TNF-alpha). Cell surface adhesion molecule expression was quantified by the sensitive radiolabeled dual monoclonal antibody technique. Neutrophil sequestration in lung tissue was measured by the myeloperoxidase assay. Lung injury was determined histologically and lung edema was assessed by wet/dry ratios. Pancreatic injury was demonstrated to occur in all CDE-fed mice, which developed significant hyperamylasemia and hypoglycemia by 48 hours (P <0.0001). Serum TNF-alpha levels increased significantly by 48 hours over baseline values (P <0.02). Expression of intracellular adhesion molecule (ICAM-1) in pulmonary endothelia was significantly increased above baseline by 30% at 48 hours (P <0.02) and peaked at 120 hours by 100% (P <0.0001). Vascular cellular adhesion molecule (VCAM-1) was constitutively expressed at baseline and was upregulated threefold by 48 hours (P <0.0001). Neutrophil infiltration increased gradually 24 hours after ICAM-1 and VCAM-1 were upregulated with significant elevation of myeloperoxidase activity over baseline at 72 hours (7.2 +/- 1.2 vs. 18.1 +/- 2.2 activity units/gram tissue; P <0.05). Neutrophil infiltration peaked at 144 hours (26.24 +/- 10.49 activity units/gram tissue P <0.0001), and its kinetics correlated with the onset and progression of morphologic injury as well as increased lung edema. These results show that acute pancreatitis is associated with a systemic release of inflammatory cytokines, followed by increased expression of pulmonary ICAM-1 and VCAM-1, neutrophil infiltration, and histologic lung injury. The adhesion molecule axis may be a potential target for practical intervention to ameliorate lung injury and morbidity in acute pancreatitis.
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PMID:Temporal correlation of tumor necrosis factor-alpha release, upregulation of pulmonary ICAM-1 and VCAM-1, neutrophil sequestration, and lung injury in diet-induced pancreatitis. 1076 87

The course of pulmonary edema formation after an intratracheal (i.t.) instillation of ovalbumin was followed noninvasively by magnetic resonance imaging (MRI) in actively sensitized Brown Norway (BN) rats. Changes in edema volume assessed by MRI mimicked the results from the analysis of the number and activation of inflammatory cells recovered from the broncho-alveolar lavage (BAL) fluid. Rats treated with budesonide did not develop edema following challenge with ovalbumin, and these animals showed a significant decrease in BAL fluid inflammatory cell numbers and eosinophil peroxidase and myeloperoxidase activities. Thus, following lung edema formation by MRI provides a reliable means of assessing pulmonary inflammation after allergen challenge. Unlike BAL fluid analysis, which requires killing animals at each time point, this method is noninvasive. MRI could be of importance for the noninvasive profiling of anti-inflammatory drugs in animal models of asthma and in the clinic. Magn Reson Med 45:88-95, 2001.
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PMID:Pulmonary edema induced by allergen challenge in the rat: noninvasive assessment by magnetic resonance imaging. 1114 90

We investigated the roles of neutrophil and neutrophil elastase in acute lung injury (ALI) to elucidate the mechanism of ALI. We designed two protocols. Protocol I: Experimental ALI was induced by endotoxin (0.02 mg/kg) and platelet-activating factor (8 microg/kg/4 h) in untreated rabbits (control group I), in neutropenic rabbits pretreated with nitrogen-N-oxide hydrochloride, and in untreated rabbits infused with a neutrophil elastase inhibitor (ONO-5046; 20 mg/kg/4 h). Protocol II: ALI was induced by smaller doses of endotoxin (0.015 mg/kg) and platelet-activating factor (7 microg/kg/4 h) than those used in protocol I in untreated rabbits (control group II), in neutrophilic rabbits pretreated with human recombinant granulocyte colony-stimulating factor, and in neutrophilic rabbits infused with ONO-5046 (as in protocol I). The severity of ALI was assessed by the protein concentration, the elastase activity in the bronchoalveolar lavage fluid, and the histologic pulmonary edema ratio. The degree of pulmonary neutrophil accumulation was assessed by pulmonary myeloperoxidase activity and histological findings. Both ALI and pulmonary neutrophil accumulation were suppressed by neutropenia (protocol I), while they were exacerbated by neutrophilia (protocol II). The neutrophil elastase inhibitor could suppress ALI, but it could not suppress pulmonary neutrophil accumulation in both untreated and neutrophilic rabbits (protocols I and II). These findings indicate that neutrophils play an important role in the pathogenesis of ALI via neutrophil elastase.
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PMID:Neutrophils mediate acute lung injury in rabbits: role of neutrophil elastase. 1118 17


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