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)

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 effects of synthetic platelet-activating factor (PAF) on guinea pig lung were examined in isolated lungs perfused with platelet-free Krebs-Ringer solution. When PAF (1 microgram) was injected into the pulmonary artery (PA), it markedly increased airway pressure (maximal increase, 84.7%) and moderately raised PA pressure (maximal increase, 22.8%). The same dose also provoked a massive (29-fold) release of thromboxane B2 (TXB2), the stable metabolite of TXA2, into the perfusate, beginning before the increases in airway and PA pressures. The concentration of 6 keto-PGF1 alpha, the stable metabolite of prostacyclin, also increased (to 5 times control levels) about 70 s after peak release of TXB2. Indomethacin completely blocked TXB2 release, reduced the magnitude of airway pressure increase by 79%, and shortened its duration, as well as the duration of the PA pressure rise. Larger concentrations of PAF (3 and 10 micrograms) produced even greater increments in airway and PA pressures, but these were only moderately attenuated by indomethacin. Also, PAF increased extravascular lung water, as evidenced by increases in wet/dry lung weight and lung/body weight ratios. In a concentration of 0.1 microgram, PAF had no effects on airway or PA pressures, nor did it stimulate TXB2 or 6-keto-PGF1 alpha release. Lyso-PAF was similarly ineffective. We conclude that PAF induces airway constriction, pulmonary hypertension, and pulmonary edema in guinea pig lung independently of platelets. These effects are associated with stimulated synthesis of TXA2, but the mechanisms of their production remain to be determined.
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PMID:Platelet-activating factor raises airway and vascular pressures and induces edema in lungs perfused with platelet-free solution. 654 31

The purpose of the study was to investigate the possible involvement of prostaglandins (PG) and thromboxanes (TX) in the cardiovascular and pulmonary changes associated with the use of continuous positive-pressure ventilation (CPPV). Indomethacin (IND), an inhibitor of PG cyclo-oxygenase, was used to block the synthesis and release of PG and TX in the lung after alveolar stretch with CPPV. Groups of dogs received CPPV (buffer group) or CPPV + IND 5 mg/kh iv (CPPV + IND). Pulmonary edema or alveolar hemorrhage was evident in 5 of 6 buffer animals. This damage was also manifested by a 50% decrease in lung compliance. However, IND appeared to block development of lung tissue damage in 5 of 6 CPPV + IND dogs and compliance remained normal. A 52% lowering of cardiac index (CI) in the buffer group paralleled a 71% reduction of left ventricular dP/dt max (first derivative of left ventricular pressure). Peak transmural right heart filling pressure decreased only 15%. in contrast, the 38% decrement of CI in the CPPV + IND animals was coupled with a 98% reduction in filling pressure, but only a 25% decrease in dP/dt max. CPPV-induced changes may have been related, in part, to the release of cytotoxic negative inotrope(s) from damaged alveolar membranes because IND pretreatment blocked this damage.
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PMID:Indomethacin pretreatment in continuous positive-pressure ventilation. 701 42

Pulmonary edema which develops during acute myocardial infarction is generally believed to result solely from pulmonary microvascular hypertension. However, patient with myocardial infarction and pulmonary edema occasionally are found to have normal pulmonary wedge pressure. We report data indicating that pulmonary edema develops after coronary artery ligation despite stable microvascular pressure. Four groups of open-chest dogs were studied: (1) nine dogs with left anterior descending coronary artery ligation, (2) seven dogs with sham coronary ligation, (3) seven dogs ligated after beginning an infusion of indomethacin (5 mg/kg per hr), and (4) five dogs ligated after an infusion of the drug's vehicle was begun. Extravascular lung water and pulmonary blood volume were measured at hourly intervals during the 2 hours before and after coronary ligation or sham ligation. Gravimetric lung water was measured immediately thereafter. Changes of net pulmonary intravascular driving force (the difference of microvascular hydrostatic and oncotic pressure) after ligation or sham ligation were small and comparable in all groups. Pulmonary blood volume did not change in any group. Pulmonary extravascular water volume remained constant in the sham group but rose significantly in the ligated group. Gravimetric lung water also was significantly higher in the latter group. We interpret these results to indicate that factors other than microvascular pressure can mediate the formation of these results to indicated that factors other than microvascular pressure can mediate the formation of edema during acute myocardial infarction; increased pulmonary microvascular permeability may be responsible. Indomethacin infusion blocked the formation of edema after coronary ligation, even though net microvascular driving force was highest in this group. Infusion of the vehicle alone did not prevent edema. The mechanism by which indomethacin exerts this protective effect is unclear but is probably a result of its inhibition of cyclo-oxygenase or cyclic nucleotide phosphodiesterase.
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PMID:Non-hydrostatic pulmonary edema after coronary artery ligation in dogs. Protective effect of indomethacin. 705 61

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

In a 13-month period, ligation of the persistent ductus was carried out in 23 prematurely born babies with severe respiratory distress syndrome who were all respirator-dependent. Mean gestational age was 30.6 weeks (26-36 weeks), mean birth weight 1490 g (850-3090 g) with 3 patients under 1000 g. Signs of cardiac failure by large left to right shunt via ductus were seen at the end of the first week of life, radiologic signs as pulmonary edema were seen 1 to 2 days earlier. Mean age at operation was 13.5 days (4-27 days), mean duration of artificial ventilation 22 days (8-59 days). Indomethacin was used orally 12 of these patients without effect to close the ductus. One patient died of cerebral hemorrhage on his 17th day of life, 10 days postoperatively, one 3 1/2 months later at home with porencephaly and hydrocephalus. Four patients show radiologic signs of bronchopulmonary dysplasia. In the following 6 months up to December 1979, another 15 patients with IRDS underwent ductus ligation. Gestational age and birth weights were about the same as in the first group. Out of this second group which has not been followed up for a longer period. 3 babies died. Early mortality in both groups is 10.5% (4 out of 38 patients).
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PMID:[Ductus ligation in idiopathic respiratory distress syndrome of the premature infant]. 744 Feb 30

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

Pulmonary edema following smoke inhalation is due to the chemical toxins in smoke and not to the heat. We have shown that acrolein, a common component of smoke, induces pulmonary edema, perhaps via release of leukotrienes. We, therefore, hypothesized that acrolein, a component of smoke from burning cotton, might have a major role in producing pulmonary edema in sheep after cotton smoke inhalation and that BW-755C, a combined cyclo- and lipoxygenase inhibitor, would prevent the edema, whereas indomethacin, a cyclooxygenase inhibitor, would not. In control anesthetized sheep (n = 7), 128 breaths of cotton smoke induced no change in pulmonary arterial pressure but induced increases (P < 0.05) in pulmonary lymph flow from 4.4 +/- 0.8 (SE) to 15 +/- 2.7 ml/h, lymph protein flux from 0.25 +/- 0.08 to 0.80 +/- 0.16 g/h, and blood-corrected wet-to-dry weight ratios from a normal value of 3.8 +/- 0.07 (n = 9) to 4.5 +/- 0.18. Indomethacin (n = 6) did not significantly prevent these changes, whereas BW-755C decreased lung lymph flow change from 5 +/- 1 to 7 +/- 2 ml/h (P = NS), lymph protein flux from 0.25 +/- 0.08 to 0.35 +/- 0.1 g/h (P = NS), and weight-to-dry ratio from normal to 3.9 +/- 2.1 (P = NS). These data suggest leukotrienes may have a role in producing cotton smoke-induced noncardiogenic pulmonary edema.
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PMID:BW-755C diminishes smoke-induced pulmonary edema. 771 45

Platelet-activating factor (PAF) is a cell membrane-derived ether lipid that plays an important role in acute lung vascular injury. We recently reported that PAF potentiates protamine-induced lung edema by enhancing pulmonary venoconstriction. As PAF is known to stimulate lung eicosanoid synthesis, we investigated the role of peptidoleukotrienes and other eicosanoids in this priming effect of PAF. Addition of PAF (1.6 nM), followed 10 min later by protamine (50 micrograms/ml), to perfusate of salt solution-perfused rat lungs resulted in marked arterial and venous constrictions and severe lung edema. Lung tissue thromboxane B2, 6-ketoprostaglandin F1 alpha and leukotriene C4 (LTC4) were markedly elevated 20 min after PAF/protamine. Pretreatment of the lungs with AA-861, a specific 5-lipoxygenase inhibitor, blocked PAF/protamine-induced leukotriene synthesis, arterial and venous constrictions, and lung edema. In addition, injection of LTC4 (1 microgram) markedly potentiated protamine-induced arterial and venous constrictions and caused lung edema similar to PAF/protamine. Indomethacin, a specific cyclooxygenase inhibitor, also reduced the vasoconstrictive and edemagenic responses to PAF/protamine. However, the pulmonary edema after LTC4/protamine was not blocked by indomethacin. In separate experiments, infusion of this "priming" dose of PAF into isolated perfused lungs induced LTC4 synthesis and augmented lung thromboxane A2 synthesis after arachidonic acid infusion. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism are involved in PAF-induced potentiation of protamine lung edema.
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PMID:Platelet-activating factor potentiates protamine-induced lung edema. Role of eicosanoids. 811 95

We have reported recently that lipopolysaccharide endotoxin and platelet activating factor cooperate in priming relationships to elicit lung microvascular injury. Lung injury was associated with elevated serum levels of tumor necrosis factor-alpha (TNF alpha) and histological findings highly reminiscent of the adult respiratory distress syndrome. The present study was designed to examine the role of TNF alpha in lipopolysaccharide/platelet activating factor-induced lung injury by utilizing a highly specific monoclonal antibody which block TNF alpha actions (anti-TNF alpha monoclonal antibody). Pretreatment with anti-TNF alpha monoclonal antibody (2.5-25 mg/kg i.v., n = 5-9) dose-dependently prevented the lipopolysaccharide/platelet activating factor-induced histopathological changes, lung edema (P < .01), lung myeloperoxidase activity (P < .01), elevation of neutrophil count in bronchoalveolar lavage fluid (P < .01) and increased serum thromboxane B2 (P < .01). Indomethacin (6 mg/kg i.v., n = 5) failed to modify the lung injury despite complete inhibition of thromboxane B2 formation (P < .05). These data suggest that TNF alpha might play a key role in initiation of the early inflammatory changes which lead to adult respiratory distress syndrome.
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PMID:Tumor necrosis factor-alpha mediates endotoxin-induced lung injury in platelet activating factor-primed rats. 826 17


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