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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lungs of 13 healthy Landrace piglets were isolated, perfused and maintained in an isogravimetric state under zone III conditions. By applying vascular occlusion methods, the total blood flow resistance (Rt) was partitioned into four components: arterial (Ra), pre- (Ra') and post-capillary (Rv'), and venous (Rv). The capillary filtration coefficient (Kfc) was evaluated using a gravimetric technique. A bolus of 55 micrograms of Escherichia coli endotoxins (LPS) per 100 g of lung was injected into the arterial reservoir of eight lungs, followed by an infusion of LPS at a rate of 55 micrograms per 100 g of lung per hour for 180 min. A bolus of theophylline (85 mg per 100 g of lung weight) was injected into the arterial reservoir after the last determination of the Kfc value. All the parameters were evaluated again when the lungs reached a new steady state. Endotoxin induced a significant increase in Rt from 54.7 +/- 7.0 at zero time to 184.7 +/- 44.2 cmH2O min L-1 (100 g)-1 180 minutes later, which can be ascribed to the increase in Ra' and Rv'. These haemodynamic modifications were related to the increases in the arterial pressure and in the pressure at the distal end of the arterial segment and to the decreases in the pressure at the proximal end of the venous segment and in the blood flow. The capillary pressure and the lung weight remained unchanged. Endotoxin infusion induced an increase in the Kfc value from 0.208 +/- 0.011 (at t = 0) to 0.391 +/- 0.034 ml min-1 (cmH2O)-1 (100 g)-1 (at t = 180). Administration of theophylline significantly reduced Rt,Ra,Ra' and Rv' towards or under the baseline values and also induced a significant increase in the lung weight and in the Kfc value. It was concluded that the endotoxin-induced increase in the total blood flow resistance can be ascribed to a vasospasm occurring at the level of the pre- and post-capillary small vessels and that changes in the permeability of the endothelium greatly contribute to the development of the pulmonary oedema observed in endotoxaemic pigs.
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PMID:Endotoxin-induced microvascular injury in isolated and perfused pig lungs. 129 7

C receptor-1 is a protein involved in the regulation of C3 and C5-convertases. Recombinant human soluble C receptor-1 has recently been produced and shown to reduce infarct size in a rat model of myocardial ischemia/reperfusion injury. The present study aimed to investigate whether recombinant human soluble C receptor-1 exerts any protective effect on pulmonary injury produced in a rodent model of adult respiratory distress syndrome. In this model, Escherichia coli endotoxin (LPS, 0.1 microgram/kg) combined with platelet-activating factor (1 pmol/kg/min over 60 min, n = 10) caused microvascular lung injury characterized by elevation of myeloperoxidase activity, deposition of C3 and C5b-9 on the endothelium of pulmonary vessels, and pulmonary edema. Furthermore, bronchoalveolar lavage revealed increased neutrophil count and elevated protein concentration. These pulmonary responses were associated with elevated serum TNF-alpha. Pretreatment (10 min, i.v.) with recombinant human soluble C receptor-1 at 10 mg/kg (n = 13), but not at 1 mg/kg, prevented the LPS/platelet-activating factor-induced pulmonary edema (p less than 0.01) and changes in the bronchoalveolar lavage fluid cell count (p less than 0.01) and protein concentration (p less than 0.05), and attenuated the deposition of C3 and C5b-9 to lung vessels. There was no effect on lung myeloperoxidase activity and serum TNF-alpha. Also, C depletion by cobra venom factor (500 U/kg, i.v.) eliminated the pulmonary edema and elevated leukocyte count in bronchoalveolar lavage fluid, but had no effect on lung myeloperoxidase activity and serum TNF-alpha. These data suggest that C factors may play an important role in the pathophysiology of adult respiratory distress syndrome.
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PMID:Role of complement in endotoxin/platelet-activating factor-induced lung injury. 132 80

TNF is a major mediator in the pathogenesis of endotoxic shock, and its inhibition has a protective effect in various animal models of sepsis or endotoxin (lipopolysaccharide, LPS) toxicity. LPS treatment also induces an oxidative damage mediated by increased production of reactive oxygen intermediates. N-Acetylcysteine (NAC) is an antioxidant and a precursor of the synthesis of glutathione (GSH) and was reported to protect against LPS toxicity and LPS-induced pulmonary edema. In this study we investigated the effect of NAC on TNF production and LPS lethality in mice. The results indicated that oral administration of NAC protects against LPS toxicity and inhibits the increase in serum TNF levels in LPS-treated mice. The inhibition was not confined to the released form of TNF, since NAC also inhibited LPS-induced spleen-associated TNF. On the other hand, the inhibitor of GSH synthesis, DL-buthionine-(SR)-sulfoximine (BSO), had the opposite effect of potentiating LPS-induced TNF production, and this was associated with a decrease in liver GSH levels. Repletion of liver GSH with NAC reversed this effect. NAC was also active in inhibiting TNF production and hepatotoxicity in mice treated with LPS in association with a sensitizing dose of Actinomycin D. These data indicate that GSH can be an endogenous modulator of TNF production in vivo. On the other hand, NAC pretreatment did not inhibit other effects of LPS, particularly induction of serum IL-6, spleen IL-1 alpha, and corticosterone, in the same experimental model, suggesting that the observed effect could be specific for TNF.
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PMID:N-acetylcysteine and glutathione as inhibitors of tumor necrosis factor production. 154 68

Endotoxin (lipopolysaccharide or LPS) inhalation has been implicated in increased pulmonary edema, most likely due to activation of an inflammatory response. The purpose of this study was to determine the cell types in the lung responsible for binding inhaled lipid A from Enterobacter agglomerans LPS. Five-hour exposures of aerosolized lipid A resulted in measurable pulmonary edema in hamsters, as determined by the accumulation of lung water. Immunocytochemistry was used to localize the inhaled lipid A in the cell types in the lung. Alveolar macrophages had decreased levels of lipid A as compared to unexposed controls, suggesting a possible metabolism by the macrophages. In vitro exposure of macrophages to lipid A resulted in a time-dependent clearance of lipid A which was inversely related to its concentration. Alveolar macrophages thus appear to be responsible for the removal of inhaled lipid A in this model and may initiate the physiological events which bring about pulmonary edema.
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PMID:Immunocytochemical determination of the role of alveolar macrophages in endotoxin processing in vitro and in vivo. 176 44

We used a selective leukotriene (LT) D4/E4 receptor antagonist (LY 203647) to investigate the role of cysteinyl LTs as mediators of several important pathophysiological events in a porcine model of endotoxic shock. Pentobarbital-anesthetized pigs (11.8-17.5 kg) were mechanically ventilated with 100% O2. Pigs in groups I (n = 10), IIA (n = 10), and IIB (n = 5) were infused with Escherichia coli lipopolysaccharide (LPS; 250 micrograms/kg) from time (t) = 0-20 min. Pigs in group III (n = 3) were normal controls. All pigs were resuscitated from t = 0-240 min with Ringer lactate (0.8 ml.kg-1.min-1). Pigs in group I received no further treatment. At t = 30 min, groups IIA and IIB were injected with LY 203647 (30 mg/kg) and were started on an infusion of the compound at 10 (group IIA) or 30 mg.kg-1.h-1 (group IIB). Delayed treatment with LY 203647 significantly (P less than 0.05) and persistently ameliorated LPS-induced pulmonary hypertension. The compound also abrogated LPS-induced pulmonary edema, as assessed by gravimetrically determined lung extravascular wet-to-dry weight ratios. Despite its beneficial effect on pulmonary edema, delayed treatment with LY 203647 did not improve arterial oxygenation. Delayed treatment with LY 203647 transiently improved mesenteric perfusion. These data suggest that cysteinyl LTs are important mediators in porcine endotoxicosis.
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PMID:Delayed treatment with an LTD4/E4 antagonist limits pulmonary edema in endotoxic pigs. 185 25

Bacterial sepsis often precedes the development of the adult respiratory distress syndrome (ARDS) and bacterial endotoxin (LPS) produces a syndrome similar to ARDS when infused into experimental animals. We determined in isolated, buffer-perfused rabbit lungs, free of plasma and circulating blood cells that LPS synergized with platelet activating factor (PAF) to injure the lung. In lungs perfused for 2 h with LPS-free buffer (less than 100 pg/ml), stimulation with 1, 10, or 100 nM PAF produced transient pulmonary hypertension and minimal edema. Lungs perfused for 2 h with buffer containing 100 ng/ml of Escherichia coli 0111:B4 LPS had slight elevation of pulmonary artery pressure (PAP) and did not develop edema. In contrast, lungs exposed to 100 ng/ml of LPS for 2 h had marked increases in PAP and developed significant edema when stimulated with PAF. LPS treatment increased capillary filtration coefficient, suggesting that capillary leak contributed to pulmonary edema. LPS-primed, PAF-stimulated lungs had enhanced production of thromboxane B2 (TXB) and 6-keto-prostaglandin F1 alpha (6KPF). Indomethacin completely inhibited PAF-stimulated production of TXB and 6KPF in control and LPS-primed preparations, did not inhibit the rise in PAP produced by PAF in control lungs, but blocked the exaggerated rise in PAP and edema seen in LPS-primed, PAF-stimulated lungs. The thromboxane synthetase inhibitor dazoxiben, and the thromboxane receptor antagonist, SQ 29,548, similarly inhibited LPS-primed pulmonary hypertension and edema after PAF-stimulation. These studies indicate that LPS primes the lung for enhanced injury in response to the physiologic mediator PAF by amplifying the synthesis and release of thromboxane in lung tissue.
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PMID:Primed stimulation of isolated perfused rabbit lung by endotoxin and platelet activating factor induces enhanced production of thromboxane and lung injury. 231 70

Administration of E. coli LPS prior to 3.5 mg/Kg dose of thiourea has been reported to protect rats against pulmonary edema and pleural effusion. However, LPS of Shigella sonnei (either in phase I or II) did not show any protective effect. These data might suggest a different mechanism of endotoxins on membranes.
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PMID:[Action of various bacterial endotoxins on pleurisy and pulmonary edema induced by thiourea]. 643 66

We attempted to mimic septic conditions in vitro by using a model of isolated perfused rabbit lung (IPRL) and evaluated the effects of endotoxin or endotoxin-induced mediators (or both) on it. Moreover, we determined the salutary effects of HWA 138, a new xanthine derivative, against endotoxin-related lung injury. To study this, heparinized human blood was centrifuged, following which the plasma complement was inactivated by heat treatment and the isolated and washed buffy coat cells were then added to it. This was followed by incubation of aliquot suspension with and without endotoxin (lipopolysaccharide [LPS], 100 ng/ml) at 37 degrees C for 2 hours. Plasma was then harvested and is referred to as sepsis-like plasma (SLP). Control plasma (CP) was not exposed to LPS. IPRLs were then perfused with SLP, CP, LPS itself, or both LPS and CP without additional white blood cells. Endotoxin itself did not induce any changes in the presence or in the absence of control plasma; however, sepsis-like plasma led to the development of lung edema, as evidenced by significantly elevated lung water and pulmonary artery pressure. Administration of HWA 138 before the addition of SLP prevented the SLP-induced lung injury. These results lead us to conclude that lung injury is caused by LPS-induced mediators rather than being directly caused by LPS. The results also suggest that HWA 138 may be a useful agent in the treatment of sepsis-induced pulmonary injury.
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PMID:Acute lung injury by endotoxin-induced mediators: prevention by HWA 138, a new xanthine derivative. 770 4

This study addresses the hypothesis that endotoxin (LPS) is an important proximal mediator of remote organ dysfunction following intestinal reperfusion. Sprague-Dawley rats underwent intestinal ischemia for 120 min followed by 60 min of reperfusion (IIR). Animals underwent pretreatment with polymyxin B (PMB, 200 micrograms, sc) or the induction of tolerance to LPS prior to assignment to the IIR or sham group. Controls received equal volumes of normal saline. Lung and intestinal injury was quantitated using an edema index. Bile flow was quantitated by measuring the volume of bile produced per 15 min. The intestinal edema index of IIR animals pretreated with PMB was nearly 50% less than that of saline-treated animals sustaining the same injury (P < 0.05). The induction of LPS tolerance reduced the edema index of IIR animals by 28% compared to the saline-treated IIR group (P < 0.05). Neither treatment reduced this parameter to that of sham-operated controls (P < 0.05). The lung edema index of animals pretreated with PMB was 50% of that of saline-treated IIR animals (P < 0.05). This remained significantly greater than that of sham-operated controls (P < 0.05). LPS tolerance did not affect the lung edema index of animals sustaining IIR. Bile flow rates following IIR were not significantly affected by PMB or LPS tolerance. These data do not support the hypothesis that LPS is an important proximal mediator of the remote organ injury associated with IIR. However, they do suggest that LPS may be one of many mediators responsible for this injury.
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PMID:Endotoxemia and remote organ injury following intestinal reperfusion. 801 13

The following study was performed to determine the effects of phosphodiesterase IV (PDE-IV) inhibition and its attenuation of tumor necrosis factor (TNF alpha) production in a rat model of the Adult Respiratory Distress Syndrome (ARDS). Rats were either unexposed (n = 8), pretreated orally with vehicle prior to intratracheal saline exposure (n = 11), pretreated with vehicle prior to 7 mg/kg intratracheal endotoxin (LPS) administration (n = 22), or pretreated with 5 or 50 mg/kg rolipram prior to LPS exposure (n = 6 and 7, respectively). Blood was sampled 1 and 3 hr post LPS exposure and assayed for plasma TNF alpha concentrations. Twenty-four hours after LPS exposure, blood was sampled again for hematologic measurements. The rats were then anesthetized and exsanguinated. Bronchoalveolar lavage (BAL) was performed after the lung of each rat was removed and weighed. Rolipram pretreatment was protective against LPS-induced mortality and also resulted in reduced plasma TNF alpha concentrations. LPS induced pulmonary edema, as indicated by wet/dry lung weight ratio (W/D) and total BAL protein content (TP) was attenuated by rolipram pretreatment. LPS-induced alveolar hemorrhage was reduced by rolipram pretreatment, but LPS-induced pulmonary neutrophilia was not. The hemoconcentration induced by LPS was reduced by rolipram, as was the LPS-induced thrombocytopenia. However, LPS-induced changes in circulating leukocyte populations were actually exacerbated by rolipram. LPS-induced alterations in renal and hepatic function, indicated by increased blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were inhibited by rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic intervention in a rat model of ARDS: IV. Phosphodiesterase IV inhibition. 838 94


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