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)

The purpose of this study was to determine if aspirin, in doses that elevate plasma salicylate concentrations to values reported in patients with salicylate-induced pulmonary edema, produce pulmonary vasoconstriction in a canine, isolated perfused left lower lung lobe (LLL) preparation. In 10 LLL's, aspirin (avg 97.8 mg/dl plasma) caused LLL arterial pressure to rise from 9.1 +/- 0.3 to 23.0 +/- 1.8 (SE) Torr. In contrast, no vascular pressure changes were observed in placebo-treated control LLL's. Sodium meclofenamate and indomethacin, structurally dissimilar cyclooxygenase inhibitors, elicited similar responses to aspirin, suggesting that a mechanism involving products of prostaglandin cyclooxygenase was involved in producing the vasoconstriction. The double-occlusion technique was used to localize the sites of the vasoconstriction. The results suggested that all three drugs caused both lobar arterial and venous tone to increase. Although high doses of aspirin produced pulmonary vasoconstriction in the isolated, perfused LLL, the aspirin-treated LLL's gained less weight and extravascular water than the control lobes.
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PMID:Effect of high doses of aspirin on pulmonary hemodynamics and lung water. 397 Feb 25

We describe neutrophil chemoattractant activity that is produced by cultured bovine aortic and pulmonary arterial endothelial cells when incubated with thiourea, a substance that causes increased permeability pulmonary edema in animals. The chemoattractant activity was present in culture supernates and cell lysates of endothelial cells incubated with thiourea but was not present in untreated cells. Production of chemoattractant activity was not associated with cell death; viable cell counts and cell homogenate angiotensin converting enzyme levels were not affected, and Cr release was only slightly elevated after incubation with thiourea. At least 1.5 h of incubation with 0.5 mM thiourea was necessary for generation of neutrophil chemoattractant activity. Culture supernates from pulmonary vascular smooth muscle cells and lung fibroblasts did not show increased neutrophil chemoattractant activity after incubation with thiourea. The chemoattractant had both chemokinetic and chemotactic properties, was heat stable, and was extractable into organic solvents. Meclofenamate, a cyclooxygenase inhibitor, minimally inhibited chemoattractant production, whereas 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of both cyclooxygenase and lipoxygenase, completely abolished generation of chemoattractant activity, suggesting that the activity could be a product of arachidonic acid metabolism. These results demonstrate that endothelial cells can produce a substance(s) with neutrophil chemotactic activity. Production of neutrophil chemoattractant activity by endothelial cells could be important in polymorphonuclear leukocyte accumulation at injured vascular sites.
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PMID:Thiourea causes endothelial cells in tissue culture to produce neutrophil chemoattractant activity. 643 Jan 36

We examined the hypothesis that arachidonic acid can lead to pulmonary edema, increased pulmonary vascular permeability, and increased pulmonary vascular resistance (PVR) in an isolated dog lung. The lung was perfused with a dextran-salt solution to remove blood elements. Compared to controls, 20 mg/min sodium arachidonate into the pulmonary circulation led to edema and to an increase in a permeability and surface area index (PSI%), PVR, and cyclooxygenase (i.e. prostaglandin) production as measured by 6-keto-PGF1 alpha, TXB2 and PGF2 alpha. With 20 mg/min arachidonate, indomethacin inhibited the increase in cyclooxygenase production, reduced the increase in PVR and increased the edema and PSI%. Indomethacin, alone, did not produce edema or an increase in PSI% or PVR. Lower doses of arachidonate (0.1 to 5 mg/min) led to increasing cyclooxygenase production without obvious edema or an increase in PSI% or PVR. We conclude: 1) arachidonate can lead to pulmonary edema and an increase in PVR, and may lead to an increase in pulmonary vascular permeability; these effects of arachidonate do not require normal numbers of circulating blood elements; 2) arachidonate appears to contribute to pulmonary edema and increased PSI% by a noncyclooxygenase effect since inhibition of cyclooxygenase production did not prevent, and lower doses of cyclooxygenase production did not produce edema or an increase in PSI%; 3) the increase in PVR appeared to have a cyclooxygenase component since inhibition of cyclooxygenase production reduced the increase, and 4) indomethacin can increase the magnitude of edema and PSI% from arachidonate by an undefined mechanism.
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PMID:Inhibition of cyclooxygenase production does not prevent arachidonate from increasing extravascular lung water and albumin in an isolated dog lung. 643 62

The possible contribution of metabolites of arachidonic acid to the increased permeability of the alveolar-capillary barrier in the adult respiratory distress syndrome was examined by quantifying the pulmonary edema fluid concentrations of lipoxygenase and cyclooxygenase products. The concentration of leukotriene D4 in pulmonary edema fluid of 10 patients with the adult respiratory distress syndrome (18.5 +/- 6.8 pmol/ml; mean +/- SD), assessed by specific radioimmunoassay after isolation of the mediator, was significantly higher (P less than 0.001) than that of five patients with cardiogenic pulmonary edema (4.4 +/- 1.1 pmol/ml). The concentrations of leukotrienes B4 and C4, prostaglandin E2, and thromboxane B2 in edema fluid were not significantly different in the adult respiratory distress syndrome patients than in the other subjects with pulmonary edema. The edema fluid concentration of leukotriene D4 correlated with the ratio of edema fluid to plasma concentrations of albumin (r = 0.64). Leukotriene D4 thus may contribute to the permeability defect which allows an accumulation of protein-rich alveolar fluid in the adult respiratory distress syndrome.
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PMID:Elevated concentrations of leukotriene D4 in pulmonary edema fluid of patients with the adult respiratory distress syndrome. 651 65

Blockade of the arachidonic acid cascade has been shown to improve survival and hemodynamic alterations in animal models of sepsis and acute respiratory failure (ARF). The effects of intravenous ibuprofen, a cyclooxygenase inhibitor, were observed in 20-30 kg pigs with ARF induced by a continuous LD100 infusion of live Pseudomonas aeruginosa (2 X 10(8)/20 kg/min). Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250-ml tidal volume and 0.5 FiO2. Pigs were randomly assigned to three groups: Group I received 2 bolus infusions of ibuprofen (12.5 mg/kg) at 20 and 210 min after baseline; Group II had Ps. aeruginosa (2 X 10(8) CFU/20 kg/min) only; Group III received Ps. aeruginosa and 12.5 mg/kg of ibuprofen at 20 and 210 min of ARF. Ibuprofen alone caused no significant changes in cardiorespiratory parameters. With Ps. aeruginosa infusion, significant pulmonary hypertension, hypoxemia, increased intrapulmonary shunt fraction, and systemic hypotension occurred. In the septic animals treated with ibuprofen, oxygenation was improved by a significant decrease in shunt, pulmonary edema, and pulmonary hypertension.
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PMID:Effects of ibuprofen on a porcine model of acute respiratory failure. 670 94

Liberation and metabolism of arachidonic acid may be the common final pathway of different stimuli on the pulmonary vascular bed. In a model of isolated, ventilated rabbit lungs, perfused with Krebs Henseleit albumin buffer in a recirculating system, changes of pulmonary vascular resistance and of vascular permeability are monitored continuously. The addition of free arachidonic acid or of the Ca-ionophore A 23187 to the perfusion fluid consistently evokes a biphasic increase in vascular resistance as well as an initially reversible increase in vascular permeability, followed by pulmonary edema. Both phases of increased vascular resistance are completely suppressed by inhibition of the cyclooxygenase, decreased to a large degree by inhibitors of thromboxane synthetase, and markedly augmented by short preincubation of arachidonic acid with ram seminal vesicular microsomes and by sulfhydryl reagents. The increased pulmonary vascular permeability is augmented by inhibition of cyclooxygenase and reduced by simultaneous lipoxygenase inhibition. Antagonists of histamine, serotonin and sympathic or parasympathic activity do not have any influence. PG F2alpha., TxB2, PG E2 and PG I2 alter the pulmonary vascular resistance, but do not increase vascular permeability. In conclusion, increased availability of free arachidonic acid evokes a rise in pulmonary vascular resistance, which can be ascribed to cyclooxygenase products, especially to thromboxane, and causes a rise in vascular permeability which can be ascribed to lipoxygenase products. The findings may be related to acute pulmonary lesions with increase in vascular resistance and with vascular leakage.
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PMID:Increased pulmonary vascular resistance and permeability due to arachidonate metabolism in isolated rabbit lungs. 680 41

Ethchlorvynol (10 mg/kg) causes transient pulmonary hypertension and an increased permeability pulmonary edema in sheep. To determine the role of cyclooxygenase and its metabolites, histamine, and catecholamines in both phenomena, we studied five groups of sheep: group I, placebo; group II, ethchlorvynol; group III, indomethacin with ethchlorvynol; group IV, diphenhydramine with ethchlorvynol; group V, phentolamine with ethchlorvynol. Indomethacin, but not diphenhydramine or phentolamine, blunted the pulmonary hypertensive response seen immediately following the ethchlorvynol injection. However, none of the drugs had any effect on the increased permeability pulmonary edema. We conclude that cyclooxygenase or its metabolites partially mediates the hypertensive response but not the increased permeability pulmonary edema seen in sheep following ethchlorvynol injection.
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PMID:Indomethacin blunts ethchlorvynol-induced pulmonary hypertension but not pulmonary edema. 712 77

Release and metabolism of arachidonic acid are supposed to form the common final pathway of different stimuli on the pulmonary vascular endothelium. In a model of isolated, ventilated and perfused rabbit lungs we investigated the influence of increased availability of free arachidonic acid on pulmonary vascular resistance and permeability. Addition of arachidonic acid to the perfusion fluid or release of arachidonic acid by Ca-ionophore A 23187 regularly produces a characteristic biphasic increase of the pulmonary vascular resistance as well as a continuous increase in permeability, followed by pulmonary edema. Inhibition of cyclooxygenase by indomethacin prevents the augmentation of vascular resistance, the increase of vascular permeability however is enhanced. thus the raise in pulmonary vascular resistance can be ascribed to cyclooxygenase products, the increased pulmonary vascular permeability to lipoxygenase products of arachidonic acid.
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PMID:[Increase of pulmonary vascular resistance and permeability due to the metabolism of free arachidonic acid (author's transl)]. 727 87

Generalized circulatory changes, manifesting as pulmonary oedema, acute renal failure, liver damage and severe hypotension, are well recognized aspects of acute falciparum malaria. The organ pathology is thought to be associated with a restricted local blood flow. These aspects of falciparum malaria are strikingly analogous to the shock syndrome which follows trauma, the injection of indotoxin, or some bacterial infections. Two of the cyclooxygenase products of arachidonic acid, thromboxane A2 and prostacyclin, acting through their opposing effects on vasoactivity and platelet aggregation, are emerging as the major controlling influences of vascular homeostasis. The effects of thromboxane, which constricts blood vessels and aggregates platelets, appear to dominate during traumatic or endotoxic shock. Thus thromboxane is potentially one of the main mediators of endotoxicity, and as such, from our previously published model, is likely to be important in the pathogenesis of the circulatory disturbances seen in acute malaria. This suggestion is consistent with earlier evidence that the autonomic nerve supply and bradykinin may have an important role in the pathogenesis of the haemodynamic changes in this disease. It also implies that pharmacological antagonists of thromboxane may provide useful specific therapy for the main life-threatening aspects of acute falciparum malaria.
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PMID:Thromboxane may be important in the organ damage and hypotension of malaria. 727 28

The preventive effect of indomethacin on thrombin-induced pulmonary edema was studied in rats. Administration of thrombin caused a significant increase in lung weight, wet weight to dry weight ratio (WW/DW), and relative lung water content. During infusion of thrombin, mean pulmonary artery pressure rose and mean systemic artery pressure fell, PaO2 decreased progressively and there was a continuous rise in pH and PaCO2. An inhibitor of cyclooxygenase, indomethacin, at a dose of 1 mg/kg body weight, induced a significant further increase in lung weight (p < 0.05), and a tendency towards an increase in WW/DW and water content compared with animals given thrombin alone. Treatment with indomethacin, however, counteracted the elevated pulmonary artery pressure occurring in the early phase after thrombin infusion, but not that in the late phase. Systemic artery pressure was not affected by indomethacin. The increases in pH and PaCO2 after thrombin infusion were attenuated and remained stable almost at baseline level after indomethacin administration. Indomethacin did not prevent the hypoxemia induced by thrombin infusion. In conclusion, although indomethacin prevented the early increase in pulmonary artery pressure due to thrombin and the decrease in pH and the increase in PaCO2, it caused lung vascular permeability to protein to increase more than with thrombin alone.
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PMID:Effect of indomethacin on thrombin-induced pulmonary edema in the rat. 757 Nov 66


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