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)

Increased serum levels of mucin-associated antigen have been previously demonstrated in patients with cystic fibrosis (CF) and interstitial pneumonia, and in lung-transplant recipients. The present study assessed the serum airway mucin levels in patients with acute respiratory distress syndrome (ARDS). An enzyme-linked immunosorbent assay (ELISA) method with a human-airway-mucin-specific monoclonal antibody (17Q2) was used to measure serum mucin levels in normal subjects, chronic smokers, patients with chronic bronchitis and other pulmonary diseases, patients with acute cardiogenic lung edema, and patients with ARDS. The serum mucin levels measured 9.9 +/- 0.8 ng/ml (mean +/- SEM, n = 59) in normal subjects, 12.7 +/- 1.6 ng/ml (n = 29) in chronic smokers, 21.8 +/- 1.9 ng/ml (n = 28) in patients with chronic bronchitis and other pulmonary diseases, 9.0 +/- 3.1 ng/ml (n = 5) in patients with acute cardiogenic lung edema. The serum mucin level was 53.8 +/- 6.6 ng/ml (n = 13) in patients with ARDS (p < 0.05, as compared with the four other groups). Serial measurements of serum mucin levels were obtained in patients with ARDS. Statistical analysis showed an inverse correlation of serial measurements of serum mucin with static respiratory-system compliance (p = 0.021), an inverse correlation of sequential serum mucin levels and log(Pa(O2)/Fl(O2)) (p = 0.016), and a positive correlation of sequential serum mucin levels and lung injury score (LIS) (p = 0.019). Gel-filtration analysis showed that mucin-associated antigens in ARDS sera were polydispersed and smaller than the antigens in normal sera. This study indicates that an increasing amount of degraded mucin occurs in patients with ARDS.
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PMID:Elevated serum levels of mucin-associated antigen in patients with acute respiratory distress syndrome. 937 60

We studied the mechanism of impairment of gas exchange following sedation with the alpha2 adrenoreceptor agonist, xylazine, in Suffolk cross-bred sheep spontaneously breathing room air. Xylazine caused a significant fall in PaO2 from a mean (pre-xylazine) of 97.9 mm Hg (6.7 mm Hg SEM) to a mean of 38.1 mm Hg (3.2 mm Hg SEM) one minute after injection with a transient increase in PaCO2 from a mean (pre-xylazine) of 32.6 mm Hg (1.9 mm Hg SEM) to a mean of 40.2 mm Hg (3.0 mm Hg SEM). There was no significant fall in mean arterial pressure or in white cell count. There was no significant change in a number of indices of free radical release which included ascorbyl radical, plasma antioxidant potential and alpha-tert-butyl phenyl nitrone (PBN) spin adduct measured simultaneously in both arterial and venous blood. In all sheep given xylazine there was no histological evidence of platelet emboli but lung histopathology showed evidence of pulmonary oedema and intense microvascular congestion with red cells extravasated into alveoli. No such histological changes were seen in the lungs of normal sheep. The impaired gas exchange during sedation with xylazine in sheep is caused, not by an oxidant mediated inflammatory mechanism or by platelet emboli, but by intense alveolar oedema which is probably due to pulmonary venospasm.
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PMID:Impairment of gas exchange due to alveolar oedema during xylazine sedation in sheep; absence of a free radical mediated inflammatory mechanism. 976 76

In the process of developing a model of Escherichia coli endotoxin-induced acute lung injury and shock in specific pathogen-free pigs, the effects of pretreatment with metyrapone (a cortisol-synthesis inhibitor) were examined. Metyrapone was administered 1.5 h before start of endotoxin infusion at t = 0 h (MET-ETOX group, n = 6). At the end of the experiments (t = 4 h) a bronchoalveolar lavage (BAL) was performed. Control animals received only endotoxin (CON-ETOX group, n = 6) or metyrapone (MET-CON group, n = 4). The following results are presented as means +/- SEM. It was found that metyrapone successfully blocked endogenous cortisol synthesis (plasma cortisol levels were 41.0 +/- 5.9 nM in MET-ETOX vs. 339.0 +/- 37.7 nM in CON-ETOX at t = 4 h, P <0.01). At t = 4 h the MET-ETOX animals had substantially increased systemic hypotension compared to the CON-ETOX group (mean arterial pressure 26.7 +/- 4.3 vs. 77.7 +/- 12.2 mmHg, P <0.01), decreased dynamic lung compliance (10.9 +/- 0.7 vs. 13.7 +/- 0.6 ml/cmH2O, P <0.01), increased percentage of BAL neutrophils (28.4 +/- 6.5 vs. 6.6 +/-1.8, P <0.01), pulmonary edema (BAL total protein 0.82 +/- 0.21 vs. 0.42 +/- 0.09 mg/mL, P <0.05), elevated levels of interleukin-8 (1924 +/- 275 vs. 324 +/- 131 pg/mL, P <0.01) and acidosis (pH 7.11 +/- 0.03 vs. 7.23 +/- 0.06, P <0.05). The MET-ETOX group also showed an increased pulmonary hypertension between 2 and 3 h after start of endotoxin infusion and a trend toward significantly increased levels of plasma interleukin-8 (P = 0.052). Arterial pCO2, pO2/FiO2, plasma endothelin-1, plasma TNFalpha, and blood leukocytes were not markedly influenced by the plasma cortisol levels. Nitric oxide production did not seem to be altered by endotoxin infusion in this model, in contrast to other animal studies; this discrepancy could be thought to be due to endotoxin-dosage differences or species differences. It is concluded that if endogenous cortisol production is blocked by metyrapone, the reactions occurring as a result of the endotoxin-induced acute lung injury and shock are greatly enhanced and that therefore pretreatment with metyrapone might be an important addition to this model with specific pathogen-free pigs.
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PMID:Effect of cortisol-synthesis inhibition on endotoxin-induced porcine acute lung injury, shock, and nitric oxide production. 1056 13

The mammalian peripheral lung contains at least three aquaporin (AQP) water channels: AQP1 in microvascular endothelia, AQP4 in airway epithelia, and AQP5 in alveolar epithelia. In this study, we determined the role of AQP4 in airspace-to-capillary water transport by comparing water permeability in wild-type mice and transgenic null mice lacking AQP1, AQP4, or AQP1/AQP4 together. An apparatus was constructed to measure lung weight continuously during pulmonary artery perfusion of isolated mouse lungs. Osmotically induced water flux (J(v)) between the airspace and capillary compartments was measured from the kinetics of lung weight change in saline-filled lungs in response to changes in perfusate osmolality. J(v) in wild-type mice varied linearly with osmotic gradient size (4.4 x 10(-5) cm(3) s(-1) mOsm(-1)) and was symmetric, independent of perfusate osmolyte size, weakly temperature dependent, and decreased 11-fold by AQP1 deletion. Transcapillary osmotic water permeability was greatly reduced by AQP1 deletion, as measured by the same method except that the airspace saline was replaced by an inert perfluorocarbon. Hydrostatically induced lung edema was characterized by lung weight changes in response to changes in pulmonary arterial inflow or pulmonary venous outflow pressure. At 5 cm H(2)O outflow pressure, the filtration coefficient was 4.7 cm(3) s(-1) mOsm(-1) and reduced 1.4-fold by AQP1 deletion. To study the role of AQP4 in lung water transport, AQP1/AQP4 double knockout mice were generated by crossbreeding of AQP1 and AQP4 null mice. J(v) were (cm(3) s(-1) mOsm(-1) x 10(-5), SEM, n = 7-12 mice): 3.8 +/- 0. 4 (wild type), 0.35 +/- 0.02 (AQP1 null), 3.7 +/- 0.4 (AQP4 null), and 0.25 +/- 0.01 (AQP1/AQP4 null). The significant reduction in P(f) in AQP1 vs. AQP1/AQP4 null mice was confirmed by an independent pleural surface fluorescence method showing a 1.6 +/- 0.2-fold (SEM, five mice) reduced P(f) in the AQP1/AQP4 double knockout mice vs. AQP1 null mice. These results establish a simple gravimetric method to quantify osmosis and filtration in intact mouse lung and provide direct evidence for a contribution of the distal airways to airspace-to-capillary water transport.
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PMID:Role of aquaporin-4 in airspace-to-capillary water permeability in intact mouse lung measured by a novel gravimetric method. 1061 15

The role of nitric oxide (NO) in precipitating pulmonary oedema in acute lung injury remains unclear. We have investigated the mechanism of involvement of NO in the maintenance of liquid balance in the isolated rabbit lung. Thirty pairs of lungs were perfused with colloid for up to 6 h, during which pulmonary vascular resistance (PVR) and capillary pressure (PCP) were measured frequently, and time to gain 5 g in weight (t5) was recorded. Four protocols with different perfusate additives were studied: (i) none (control, n = 11); (ii) 10 mmol NG-nitro-L-arginine methyl ester (L-NAME) (n = 6); (iii) 10 mmol L-NAME with 100 mumol lodoxamide, an inhibitor of mast cell degranulation (n = 7); (iv) 10 mmol L-NAME with 10 mumol 8-bromo-3',5'-cyclic guanosine monophosphate (8Br-cGMP), an analogue of cGMP that may reduce vascular permeability by relaxing contractile elements in endothelial cells (n = 6). Neither PVR nor PCP differed between protocols. L-NAME markedly reduced t5 from 248 (27) min (mean (SEM)) in protocol (i) to 144 (5) min in protocol (ii) (P < 0.05). Both lodoxamide (t5 = 178 (7) min) and 8Br-cGMP (t5 = 204 (10) min) substantially corrected the effect of L-NAME (P < 0.005). Results suggest that maintenance of a low permeability by NO may involve mast cell stabilization and endothelial cell relaxation.
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PMID:Inhibition of nitric oxide synthesis augments pulmonary oedema in isolated perfused rabbit lung. 1106 16

Adult Respiratory Distress Syndrome is a disease with functional lung heterogeneity and thus a ventilator-delivered breath may over-distend non-involved areas. In rats we examined ventilator-delivered tidal volume (TV) breaths of 7 and 20 ml/kg on lung water as evidence of lung injury. We examined the role of aquaporins on ventilator-induced lung injury (VILI) by infusing HgCl(2) which inhibits aquaporins by binding cysteine. Wet to dry lung weight ratio (W/D) as evidence of lung water was 4.47+/-0.1 SEM in controls, 4.6+/-0.1 and 5.5+/-0.2 (P<0.05) in rats ventilated at 7 and 20 ml/kg, respectively. Pulmonary artery pressure (PAP) rose from 23+/-1 to 26+/-1 mmHg (P<0.05, n=7) and cardiac output fell from 104+/-2 to 67+/-3 ml/min (P<0.05) in rats ventilated at 20 ml/kg. Left ventricular end diastolic pressure (n=3) was unchanged. Evans Blue dye, an albumin marker, increased from a control 37+/-11 to 97+/-41 mg/g wet lung in TV 20 rats (P<0.05). HgCl(2) infused slowly by tail vein did not significantly raise PAP, but did increase W/D to 6+/-0.2 (P<0.05) in rats ventilated at 20 ml/kg but not at 7 ml/kg. Equimolar cysteine infusions prevented the HgCl(2) from increasing the W/D above that seen with TV 20 ml/kg. Thus ventilation with TV of 20 ml/kg produced a protein-rich lung edema. Aquaporin channels may have a protective effect in VILI.
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PMID:Aquaporin channels may modulate ventilator-induced lung injury. 1116 7

An exaggerated hypoxic pulmonary vasoconstriction is essential for development of high-altitude pulmonary edema (HAPE). We hypothesized that susceptibility to HAPE may be related to decreased production of nitric oxide (NO), an endogenous modulator of pulmonary vascular resistance, and that a decrease in exhaled NO could be detected during hypoxic exposure. Therefore, we investigated respiratory tract NO excretion by chemiluminescence and pulmonary artery systolic pressure (Ppa,s) by echocardiography in nine HAPE-susceptible mountaineers and nine HAPE-resistant control subjects during normoxia and acute hypoxia (fraction of inspired oxygen [FI(O2)] = 0.12). The subjects performed oral breathing. Nasally excreted NO was separated from respiratory gas by suction via a nasal mask. In HAPE-susceptible subjects, NO excretion in expired gas significantly decreased (p < 0.05) during hypoxia of 2 h in comparison with normoxia (28 +/- 4 versus 21 +/- 2 nl/min, mean +/- SEM). In contrast, the NO excretion rate of control subjects remained unchanged (31 +/- 6 versus 33 +/- 6 nl/ min, NS). Nasal NO excretion did not differ significantly between groups during normoxia (HAPE-susceptible group, 183 +/- 16 nl/ min; control subjects, 297 +/- 55 nl/min, NS) and was not influenced by hypoxia. The changes in Ppa,s with hypoxia correlated with the percent changes in lower respiratory tract NO excretion (R = -0.49, p = 0.04). Our data provide the first evidence of decreased pulmonary NO production in HAPE-susceptible subjects during acute hypoxia that may contribute among other factors to their enhanced hypoxic pulmonary vascular response.
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PMID:Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high-altitude pulmonary edema. 1117 8

Levels of nitrite (NO2-) and nitrate (NO3-) were measured in pulmonary edema fluid and plasma from 34 patients with early acute lung injury (ALI) and 20 patients with hydrostatic pulmonary edema. Pulmonary edema fluid from patients with ALI had significantly higher levels of NO2- + NO3- compared with pulmonary edema fluid from patients with hydrostatic pulmonary edema (108 +/- 13 microM versus 66 +/- 9 microM; means +/- SEM; p < 0.05). In addition, patients with shock had higher plasma NO2- + NO3- levels than those without shock (79 +/- 11 microM versus 53 +/- 12 microM, p < 0.05). Acidemia and increased anion gap, markers of systemic hypoperfusion, were also associated with twofold higher plasma NO2- + NO3- levels (p < 0.01). Increased levels of NO2- + NO3- in edema fluid samples were associated with slower rates of alveolar fluid clearance. Nitrated pulmonary surfactant protein A (SP-A) was also detected in the edema fluid of patients with ALI after immunoprecipitation with a specific antibody against this protein. Previously, we have shown that nitration of SP-A impairs its host- defense properties. In aggregate, the results of this study indicate that reactive oxygen-nitrogen species may play a role in the pathogenesis of human ALI.
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PMID:Increased levels of nitrate and surfactant protein a nitration in the pulmonary edema fluid of patients with acute lung injury. 1120 43

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen and permeability factor that is inducible by hypoxia. Its contribution to high-altitude illness in man is unknown. We measured VEGF levels in 14 mountaineers at low altitude (490 m) and 24 h after their arrival at high altitude (4,559 m). At high altitude, VEGF increased from [mean (SEM)] 32.5 (9.2) to 60.9 (18.5) pg.ml(-1) (P < 0.004) in the arterial blood, and from 15.9 (2.9) to 49.3 (15.9) pg.ml(-1) (P= 0.0001) in the mixed venous blood. Whereas at low altitude venous and arterial VEGF levels were not statistically different from each other (P= 0.065), the VEGF concentration was significantly lower in venous than in arterial blood samples at high altitude (P=0.004). The pulmonary capillary VEGF concentration remained unchanged at high altitude [14.8 (2.5) vs 17.1 (5.4) pg.ml(-1), P=0.85]. VEGF levels in the nine mountaineers who developed symptoms of acute mountain sickness (AMS), and in the six subjects who had radiographic evidence of high-altitude pulmonary edema were similar to those in subjects without symptoms. VEGF was not correlated with either AMS scores, mean pulmonary arterial pressures, arterial partial pressure of O2, or alveolar-arterial O2 gradients. We conclude that VEGF release is stimulated at high altitude, but that VEGF is probably not related to high-altitude illness.
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PMID:Effects of high-altitude exposure on vascular endothelial growth factor levels in man. 1151 3

Airborne exposure to lung-toxic agents may damage the lung surfactant system and epithelial and endothelial cells, resulting in a life-threatening pulmonary edema that is known to be refractory to treatment. The aim of this study was to investigate in rats (1) the respiratory injury caused by nose-only exposure to perfluoroisobutene (PFIB), and (2) the therapeutic efficacy of a treatment at 4 and/or 8 h after exposure consisting of the natural surfactant Curosurf and/or the anti-inflammatory drug N-acetylcysteine (NAC). For that purpose, the following parameters were examined: respiratory frequency (RF), lung compliance (Cdyn), airway resistance (Raw), lung wet weight (LWW), airway histopathology; and in brochoalveolar lavage (BAL) fluid, total protein, total phospholipid, cell count and differentiation, and changes in the surface tension of the BAL fluid. The mean (+/- SEM) surface tension of BAL fluid derived from PFIB-exposed (C . t = 1100-1200 mg min(-1) m(-3), approximately 1LCt50; t = 20 min) animals at 24 h following exposure (11 +/- 3 mN/m) was higher than that of unexposed rats (0.8 +/- 0.4 mN/m), reflecting damage to the surfactant system and justifying treatment with exogenous surfactant. Curosurf treatment (62.5 mg/kg i.t.) decreased pulmonary edema caused by PFIB, reflected by a decreased LWW, and decreased the amount of protein in BAL fluid. NAC treatment (1000 mmol/kg ip) inhibited the interstitial pneumonia reflected by a decreased percentage of neutrophils in the alveolar space. It was concluded that a combined treatment of Curosurf + NAC improved respiration, that is, RF and Cdyn, whereby Curosurf predominantly decreased pulmonary edema and NAC predominantly reduced the inflammatory process. A combined treatment may therefore be considered a promising therapeutic approach in early-stage acute respiratory distress caused by PFIB, although the treatment regimes need further investigation.
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PMID:Protection of rats against perfluoroisobutene (PFIB)-induced pulmonary edema by curosurf and N-acetylcysteine. 1520 46


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