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

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.
 ...
PMID:Stress failure of pulmonary capillaries: role in lung and heart disease. 809 42

A 23-year-old male with complete collapse of the right lung due to spontaneous pneumothorax was admitted 11 days after its onset. Paying close attention to the re-expansion pulmonary edema (REPE), water seal drainage was performed. Following couple episodes of persistent severe cough, four hours later, he developed dyspnea and began to expectorate frothy massive sputum. Chest X-ray revealed pulmonary edema of the entire right lung field. Measurement of total proteins and neutrophil elastase in airway exudates showed 5.5 g/dl (ratio to plasma, 0.89) and 7000 micrograms/l, respectively. Because of marked difference of compliance between bilateral lungs, management with right and left-separated mechanical ventilation and PEEP applied only to the right lung was performed. Although transient mediastinal deviation to the left was observed, successful management was achieved by the maneuver. High concentrations of total proteins and neutrophil elastase in edema fluid suggest that increased vascular permeability due to endothelial cell injury via activated neutrophils is mainly responsible for REPE. In the present case, rapid expansion of the collapsed lung accelerated by severe cough seems to be a predisposing factor of REPE. In patient with prolonged pneumothorax, suppression of cough is thought to be important for the prevention of REPE even with water seal drainage.
 ...
PMID:[A case of re-expansion pulmonary edema following water seal drainage for spontaneous pneumothorax--management with right and left-separated mechanical ventilation]. 163 63

The endothelial cells of pulmonary blood vessel play an significant role in lung vessel permeability, especially in acute lung damage and adult respiratory distress syndrome. In this study, bovine pulmonary endothelial cells were isolated, cultured and identified by means of reverse microscopic, scanning electromicroscopic, transmission electro- microscopic and immunofluorescence microscopic observation. Then they were labeled with 51Cr. Hydrogen peroxide (H2O2), H2O2 with catalase, xanthine oxidase (XO) with hypoxanthine (HX), human neutrophil elastase (HNE), cathepsin-G (C-G) and endotoxin (ET) were incubated with the labeled cells for half hour in various experimental groups respectively. The amount of 51Cr in the suspension released from the damaged cells was counted with r-radiometer. The results show that HNE, ET, H2O2 and superoxide anion (the latter is produced from the reaction between XO and HX) could at some degree damage the membrane of endothelial cells, and the inflammatory mediators of human neutrophils might play an important role in the development of pulmonary edema.
 ...
PMID:[Effect of the products released from the activated human neutrophils and endotoxin on bovine pulmonary endothelial cells]. 208 56

The Fischer rat is known for its susceptibility to develop liver necrosis when challenged with paraquat (Smith et al., J. Pharmacol. Exp. Ther. 235: 172-177, 1985). We postulated that other organs, specifically the lung, may also be more susceptible to injury and examined whether lungs from Fischer (F) rats were injured more easily when challenged with active oxygen species than Sprague-Dawley (SD) rat lungs. We aimed to investigate whether increased susceptibility to oxidant injury was related to differences in lung antioxidant defenses. Perfused lungs from both rat strains were challenged by addition of H2O2 to the perfusate or by short-term hyperoxic ventilation. To assess nonoxidant modes of lung injury, we examined lung responses after exposure to protamine sulfate or neutrophil elastase. Intravascular H2O2 or 3 h in vitro hyperoxia caused lung edema in F but not SD rats, and elastase injured F rat lungs more than the lungs from SD rats. Protamine, however, injured the lungs from both strains to a similar degree. Catalase, but not superoxide dismutase or allopurinol, protected F rat lungs against edema, resulting from 3 h in vitro hyperoxia. The lung homogenate levels for reduced glutathione or conjugated dienes and the activities of lung tissue catalase, glutathione peroxidase, and cytochrome P-450 were not different between the two strains. Lung tissue ATP levels, however, were lower in F than in SD rats. Although the F rat strain appears to have an altered oxidant-antioxidant defense balance, the exact cause of the greater susceptibility to oxidant stress of the F rat strain remains elusive.
 ...
PMID:Lung injury in Fischer but not Sprague-Dawley rats after short-term hyperoxia. 226 Jun 76

Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Lung hydroxyproline content was measured as an index of interstitial fibrosis. Cardiac right ventricular hypertrophy was determined by the right ventricle to the left ventricle plus septum weight ratio (RV/LV + S). Rats receiving SC39026 alone did not differ significantly from untreated control animals with respect to any of the quantitative endpoints, although rarefaction of Type I pneumocytes was observed in the electron micrographs of these animals. Monocrotaline-treated rats, in contrast, developed a significant increase in RV/LV + S, and exhibited pulmonary edema, inflammation, fibrosis, and muscularization and occlusive mural thickening of the pulmonary small arteries and arterioles. These monocrotaline-induced structural changes were accompanied by decreased lung ACE and PLA activities, and increased PGI2 and TXA2 production, and by an increase in lung hydroxyproline content. Cotreatment with SC39026 ameliorated the monocrotaline-induced pulmonary vascular wall thickening and the cardiac right ventricular hypertrophy. These data suggest that inappropriate neutrophil elastase activity contributes to monocrotaline pulmonary vasculopathy and hypertension. On the other hand, cotreatment with SC39026 had no significant effect on the severity of the monocrotaline-induced lung inflammatory reaction, the pulmonary endothelial dysfunction, or the increase in lung hydroxyproline content.
 ...
PMID:Monocrotaline-induced cardiopulmonary injury in rats. Modification by the neutrophil elastase inhibitor SC39026. 254 80

Rats exposed to 30 ppm NO2 continuously for 3 to 6 wk developed mild centriacinar air-space enlargement and mild interstitial fibrosis. The emphysematous changes did not become more severe after 6 wk with continued NO2 exposure for as long as 14 additional weeks. Elastase inhibitory capacity (EIC) and the total protein concentration increased acutely in lung lavage fluid, consistent with the histologic evidence of pulmonary edema, then subsided but remained above control levels for the entire exposure period. The ratio of EIC to total protein remained unchanged relative to that in control animals. Neutrophils accumulated in the lung and were recoverable by lavage with the same relative concentration profile as observed for total protein. The average elastase activity per neutrophil in cells recovered from the air space by lung lavage was 60% less than in cells recovered from peripheral blood. This was true for control or NO2-exposed rats. Thus, emphysematous changes in the NO2-exposed rat were accompanied by a marked neutrophil recruitment concomitant with an increased neutrophil elastase burden in the lung, which may have directly contributed to lesion development.
 ...
PMID:Neutrophil recruitment and degranulation during induction of emphysema in the rat by nitrogen dioxide. 364 67

Neutrophils play a role in the development of pulmonary edema in many models of the adult respiratory distress syndrome, but the mechanism of their action is not completely understood. We asked whether two neutrophil secretory products, human neutrophil cationic protein (NCP) and human neutrophil elastase (HNE), would nonenzymatically alter the movement of albumin across a cultured endothelial monolayer. Both enzymes were inactivated by heating before use. HNE was additionally enzymatically inactivated with a chloromethylketone oligopeptide (CMK) inhibitor and with alpha 1-proteinase inhibitor (alpha 1-PI). Heated NCP, heated HNE, and CMK-complexed HNE all increased transendothelial albumin transfer. The cation protamine also increased albumin transfer across the endothelium and this increase was blocked by heparin. Alpha 1-PI and fetal bovine serum also prevented the cationic proteins from increasing albumin transfer. Using the release of lactate dehydrogenase as a marker of cytotoxicity, heated HNE was toxic to endothelial cells, heated NCP had only minimal toxicity, and protamine had no toxicity. Changes in endothelial cell shape with gap formation was seen after exposure to both heated HNE and heated NCP. Both the cytotoxicity associated with heated HNE and the cell shape changes associated with heated NCP and heated HNE could be blocked by heparin. These results suggest that in addition to neutrophil proteases and reactive O2 molecules, neutrophil-derived cationic proteins can directly and nonenzymatically contribute to edema formation during acute inflammation.
 ...
PMID:Cationic neutrophil proteins increase transendothelial albumin movement. 364 23

The purpose of the present study was to assess the role of polymorphonuclear leukocyte (neutrophil) elastase in endotoxin-induced acute lung injury in sheep with lung lymph fistula. We studied the effects of ONO-5046, a specific inhibitor of neutrophil elastase, on the lung dysfunction induced by the intravenous infusion of 1 microgram/kg of Escherichia coli endotoxin. Endotoxin alone produced a biphasic response as previously reported. Early (0.5-1 h) after endotoxin, pulmonary arterial pressure increased from 19.5 +/- 0.9 cmH2O at baseline to a peak of 46.8 +/- 2.4 cmH2O (P < 0.05). Pulmonary vascular resistance increased from 3.03 +/- 0.17 cmH2O.l-1.min at baseline to a peak of 9.77 +/- 0.70 cmH2O.l-1.min (P < 0.05). Circulating neutrophils decreased from 7,355 +/- 434/mm3 at baseline to a nadir of 1,762 +/- 32/mm3 (P < 0.05). Thromboxane B2 and 6-ketoprostaglandin F1 alpha concentrations in plasma and lung lymph were significantly increased. Late (3-5 h) after endotoxin, pulmonary arterial pressure and pulmonary vascular resistance returned to baseline levels, but lung lymph flow remained increased from 4.2 +/- 0.3 ml/0.5 h at baseline to 7.3 +/- 0.7 ml/0.5 h (P < 0.05), with a slight increase in lung lymph-to-plasma protein concentration ratio, suggesting increased pulmonary vascular permeability. The histopathological features of the lungs during the early period in sheep treated with endotoxin alone revealed a large increase in neutrophils per 100 alveoli and changes of pulmonary edema such as thickening of the interstitium of the lung and alveolar flooding.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of ONO-5046, a specific neutrophil elastase inhibitor, on endotoxin-induced lung injury in sheep. 783 37

The effects of a competitive neutrophil elastase (NE) inhibitor, ONO-5046, and a recombinant human superoxide dismutase on leukotriene B4 (LTB4)-induced polymorphonuclear leukocyte (PMN)-mediated increase in microvascular permeability in isolated non-blood-perfused rabbit lungs were studied. Pulmonary microvascular permeability and lung edema were evaluated by use of the fluid filtration coefficient (Kf) and the wet-to-dry lung weight ratio (W/D), respectively. Pulmonary capillary pressure was estimated by the double occlusion technique. NE activity in the perfusate was determined using a spectrophotometric method. The PMNs (2-3 x 10(8) cells) were added into the perfusate in all groups of lungs. Injection of LTB4 (5 micrograms) increased Kf and W/D without affecting pulmonary arterial or capillary pressure. The LTB4-induced lung injury was closely associated with the increase in NE activity in the perfusate. Infusion of ONO-5046 (1 or 10 mg.kg-1 x h-1) inhibited the LTB4-induced increases in Kf, W/D, and perfusate NE activity in a dose-dependent fashion. Infusion of recombinant human superoxide dismutase (80,000 U.kg-1 x h-1) attenuated the LTB4-induced increases in Kf and W/D, although it did not influence the elevation of perfusate NE activity induced by LTB4. These results suggest that both NE and superoxide anion play important roles in the LTB4-induced PMN-mediated increase in pulmonary microvascular permeability.
 ...
PMID:Roles of neutrophil elastase and superoxide anion in leukotriene B4-induced lung injury in rabbit. 817 52

The effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema was studied in rats. The chloromethylketone human neutrophil elastase inhibitor, ICI 200,355, blunted rat leukocyte elastase activity in rat lung tissue. Administration of thrombin produced a significant increase (p < .01) in lung weight. The wet weight to dry weight ratio (WW/DW) and relative water contents were also significantly elevated (p < .01). Pretreatment with ICI 200,355 (200 micrograms/kg h-1) resulted in significant reductions (p < .05) in lung weight and a tendency to decrease WW/DW and water content compared with animals given thrombin alone. It is possible that the elastase inhibitor effectively reduced the rate of thrombin-induced pulmonary edema by attenuation of increased vascular permeability.
 ...
PMID:Effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema in the rat. 846 58


1 2 3 Next >>