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)

In situ complement activation was induced in isolated, ventilated, and blood-free perfused rabbit lungs. Six to 11% human serum (vol/vol) was repeatedly admixed to the recirculating Krebs Henseleit buffer during 10-min periods, interrupted by rinsing phases with serum-free medium. This caused dose-dependent, reversible, and reproducible pulmonary artery pressor responses with pressure peaks or plateaus of 8 to 22 mm Hg. Pressor responses were paralleled by a marked release of thromboxane (TxA2) and prostaglandin I2 into the medium. Heat-inactivated serum, purified fluid-phase SC5b-9, and serum that had been activated with inulin in the absence or presence of a carboxypeptidase inhibitor all failed to elicit pressor responses. Both pressor response and prostanoid release were strictly dependent on complement factor C8, and evidence for C8 binding was obtained with the use of 125I-C8. Inhibitor studies collectively indicated that TxA2 was the predominant vasoconstrictive agent. Although repetitive short-term application of human serum induced no major lung weight gain, prolonged exposure to serum (40 to 80 min) without intermittent rinsing phases caused a delayed increase in the capillary filtration coefficient to maximally 3- to 4-fold values, with marked lung edema formation. We conclude that in situ activation of complement in the rabbit lung vasculature causes immediate intrapulmonary prostanoid generation and thromboxane-mediated vasoconstriction, independent of circulating leukocytes, but dependent on the formation of terminal membrane-complement complexes. Continuous complement activation results in a delayed increase in lung vascular permeability.
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PMID:Local complement activation, thromboxane-mediated vasoconstriction, and vascular leakage in isolated lungs. Role of the terminal complement sequence. 249 76

Escherichia coli hemolysin has been implicated as a pathogenicity factor in extraintestinal E. coli infections including sepsis. In the present study the effects of intravascular administration of hemolysin were investigated in isolated blood-free perfused rabbit lungs. Low concentrations of the toxin in the perfusate (0.05-5 hemolytic units/ml, corresponding to approximately 5-500 ng/ml), caused a dose- and time-dependent release of potassium, thromboxane A2, and prostaglandin I2, but not of lactate dehydrogenase, into the recirculating medium, as well as a dose-dependent liberation of the prostanoids into the bronchoalveolar space. These events were paralleled by a dose-dependent pulmonary hypertension, and studies with different inhibitors collectively indicated that the vasoconstrictor response was mediated predominantly by pulmonary thromboxane generation. In addition, E. coli hemolysin elicited a protracted, dose-dependent increase in the lung capillary filtration coefficient, which was independent of the prostanoid-mediated pressor response and resulted in severe pulmonary edema formation. We conclude that E. coli hemolysin can elicit thromboxane-mediated pulmonary hypertension combined with severe vascular leakage in isolated lungs in the absence of circulating inflammatory cells and humoral mediator systems, mimicking the key events in the development of acute respiratory failure in states of septicemia.
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PMID:Thromboxane-mediated hypertension and vascular leakage evoked by low doses of Escherichia coli hemolysin in rabbit lungs. 250 Apr 55

We investigated mechanisms related to the development of acute lung edema, as induced by oleic acid in adult mongrel dogs. The intravenous injection of oleic acid (0.04 ml/kg) was considered to induce a permeability edema, as an enhancement of transvascular protein clearance was observed after the injection. The effects of oleic acid injection on systemic blood pressure (SBP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), cardiac output (CO) and airway pressure (AWP) were measured. A significant decrease in CO and increase in AWP were evident after the injection, but there were no changes in SBP, PAP and PAWP. Treatment of the animals with prostaglandin I2 (PGI2) did not alter the induction of edema by oleic acid. However, the decrease in CO and increase in AWP were normalized by treatment with PGI2. Blood platelet count was not affected by oleic acid given in a dose of 0.04 ml/kg. To determine the direct effect of oleic acid on the vascular endothelium, the agent was injected through a catheter placed in the pulmonary artery. Electron microscopic examination revealed severe vacuolation on the endothelium of the pulmonary artery after only 1 min of exposure to oleic acid. Increased permeation of Evans blue into the subendothelial tissue was also observed with oleic acid treatment, compared with findings in the controls. These results indicate that the lung edema induced by oleic acid is due to an increased protein clearance, probably through a direct toxic effect on the vascular endothelium rather than an indirect toxic effect of chemical mediators released from the aggregated platelets.
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PMID:Mechanisms involved in acute lung edema induced in dogs by oleic acid. 351 Aug 75

Recently much interests have focused on the imbalance between the release of thromboxane A2 (TXA2) and prostaglandin I2 (PGI2), which may contribute to the development of pulmonary vascular injury. TXB2 has potents of platelet aggregation and vasoconstriction, while PGI2 has against in its activities. We investigated the effect of new PGI2 analogue (ONO-1301), which is a novel prostacyclin mimetic with inhibitory activity against thromboxane synthetase, on the early graft function in canine left single lung allotransplantation model. 19 donor dogs were divided into three groups. Seven dogs were comprised control group and received heparin administration (400 Unit/kg) before pulmonary arterial flushing with 50 ml/kg of 4 degrees C low potassium dextran glucose (LPDG) solution. Each six dogs were comprised I2-10 and I2-50 groups respectively, with receiving a 10-minute infusion of ONO-1301 (10 micrograms/kg/min) before flushing. The pulmonary cold preservation was performed with LPDG solution at 4 degrees C for 18 hours. After left single lung transplantation, in control group, saline solution was administered to the recipient for 10 minutes encompassing the reperfusion process (starting from 5 minutes prior to reperfusion). In I2-10 group, the ONO-1301 (10 micrograms/kg/min) was administered in the same manner. In I2-50 group, the ONO-1301 was administered from the same timing as I2-10 group, but for 50 minutes. The recipient dogs were observed for 6 hours after ligation of the right pulmonary artery and bronchus. We measured the transplanted lung function, including arterial blood gas and pulmonary hemodynamics, and plasma 6-keto-PGF1 alpha, TXB2 and lipid peroxide levels of left atrial blood. Pulmonary histological investigation was performed after preservation and sacrifice the recipient dog. All recipient dogs were survived for observation period. I2 groups provided significantly better gas exchange and pulmonary hemodynamics than control group. The 6-keto-PGF alpha levels in control group peaked after an early rise in TXB2 levels, and reached maximum at one hour after contra-lateral ligations. These prostanoid release levels rose again at 6 hours. While in I2 groups, the levels of them were significantly lower compared with control group. Histological examination of the transplanted lung after assessment, revealed disruption of alveoli forced by pulmonary edema in control group. In contrast, there was minimal fluid extravasation without alveolar disruption in both I2-10 and I2-50 groups. There were no significant differences between I2-10 and I2-50 groups. Although it dose not protect the implanted lung completely from developing edema, the ONO-1301 administration (10 micrograms/kg/min) to the donor and the recipient resulted in prevention of TXA2 and PGI2 release and improvement of the respiratory function and pulmonary hemodynamics after reperfusion. We conclude that it seems beneficial to administer the ONO-1301 to the donor and the recipient in order to regulate the prostanoid release and maintain the early graft function.
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PMID:[Beneficial effect of a stable PGI2 analogue (ONO-1301) on prostanoid release after reperfusion in canine left single lung allotransplantation model]. 945 4

Prostanoids have been implicated in the regulation of lung vascular tone both under physiological and inflammatory conditions. The conversion of arachidonic acid (AA) to prostaglandin H2 is catalyzed at least by two isoforms of cyclooxygenase, named Cox-1 and Cox-2. Cox-1 is thought to be ubiquitously expressed, enrolled in physiological processes, whereas Cox-2 is mostly assumed to be dynamically regulated, responding to inflammatory conditions. We have recently shown by immunohistochemistry that Cox-2 is constitutively expressed in control rat lungs, with a predominant localization in smooth muscle cells of partially muscular vessels. We now asked whether Cox-2 is basically involved in the physiological regulation of pulmonary vascular tone. Isolated perfused rat lungs were challenged with intravascular bolus application of free AA to elicit thromboxane-related vasoconstrictor responses and to investigate the effects of three different selective Cox-2 inhibitors (NS-398, DUP697, SC-236). AA induced the liberation of prostaglandin I2 and thromboxane A2 into the intravascular space, and it provoked marked pulmonary artery pressure responses and concomitant lung edema formation. All events were dose-dependently inhibited by 1 to 50 micromol/liter NS-398, whereas control vasoconstrictor responses to angiotensin II and the stable thromboxane analogue U46619 were not affected by this agent. Similarly, marked inhibition of the AA elicited pressor response was achieved by 25 micromol/l DUP697 and by 10 micromol/l SC-236. These data suggest a physiological role of Cox-2 rather than Cox-1 in the regulation of vascular tone in rat lungs.
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PMID:Vasoregulatory prostanoid generation proceeds via cyclooxygenase-2 in noninflamed rat lungs. 973 93

This study was carried out to understand the onset mechanism of adrenaline (ADR)-induced pulmonary edema (PE) and the effect of drugs related to the arachidonate cascade in a rabbit model. ADR was administered intravenously by a bolus injection to the rabbits at 50, 75 and 100 microg/kg. To evaluate the severity of PE, the lung-water ratio (LWR) was calculated as a ratio of the difference between wet and dry lung weight to dry lung weight. The PE incidence and LWR exhibited a dose-dependent increase, and LWR correlated with the left atrial pressure (LAP). The involvement of the arachidonate cascade was evaluated by the co-administration of flurbiprofen, a cyclooxygenase inhibitor; ozagrel, a thromboxane synthase inhibitor; and OP-2507 (15-cis-(4-n-propylcyclohexyl)-6,17,18, 19,20-pentanor-9-deoxy-6,9-alpha-nitriloprostaglandin F1 methyl ester), a prostaglandin I2 analogue. Co-treatment of the rabbits with ADR and flurbiprofen resulted in an increase in LAP and the incidence of PE, whereas co-administration of ozagrel did not exhibit any significant changes in the measured parameters. Conversely, OP-2507 reduced the LAP, PE incidence and LWR when co-administered with ADR. Rabbits co-treated with OP-2507 displayed an improved cardiac function. The results of these studies demonstrated the effectiveness of OP-2507 in protecting the lung and cardiac function from the ADR-induced PE.
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PMID:The effect of the prostaglandin I2 analogue OP-2507 on adrenaline-induced pulmonary edema in rabbits and analysis of hemodynamic changes. 1092 25