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 lung transplantation, the safety period of the ischemic time of the graft is within 6 hours. Because of the problem of donor shortage, it is essential to extend the safety period of the preservation time of the donor lung. However, the longer the preservation time is, the more severe is the resulting ischemia-reperfusion injury. This study was designed to evaluate the efficacy of initial controlled perfusion pressure in the reduction of ischemia-reperfusion injury in a 24-hour preserved lung. Japanese white rabbit lungs were flushed with a low-potassium dextran solution (4C, 500 ml) after injection of prostaglandin E1 (20 microgram, bolus via PA) and submersed in the same solution for 24 hours at 4C. After preservation, the left lung was reperfused using an extracorporeal lung perfusion model which comprised of a closed circuit combined with a membrane deoxygenator. Assessment of lung function included gas analysis of influent and effluent blood and mean pulmonary artery perfusion pressure. Then the lung wet/dry weight ratio was calculated. In group I of the control group (n=6), the left lung was reperfused immediately following flushing (without preservation) at a flow rate of 50 ml/min for 60 minutes. In groups II and III, grafts were stored for 24 hours. In group II, grafts (n=6) were reperfused at a flow rate of 50 ml/min for 60 minutes. In group III (n =6), the flow rate was controlled by maintaining the perfusion pressure below 30 mmHg during the initial 5 minutes and was increased to 50 ml/min for the subsequent 60 minutes. In group II, the mean pulmonary artery pressure during perfusion increased rapidly, and oxygenation deteriorated. All grafts developed pulmonary edema within 12 minutes after reperfusion. Examination of the specimen revealed that the peripheral lung was not perfused. In group III, the mean pulmonary artery perfusion pressure was maintained below 30 mmHg, and oxygenation was preserved sufficiently throughout the experiment (delta PO2 > 100 mmHg) with no significant difference from control values. In conclusion, ischemia-reperfusion injury of the 24-hour preserved lung was attenuated prominently by controlling initial perfusion pressure for 5 minutes.
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PMID:Efficacy of initial controlled perfusion pressure for ischemia-reperfusion injury in a 24-hour preserved lung. 1007 64

Lung edema is the main clinical manifestation of reperfusion injury following lung transplantation. The evaluation of strategies to prevent this injury is of high clinical importance. Therefore we developed a large-animal model to study the mechanisms of ischemia/reperfusion injury including dynamics of posttransplant reperfusion edema and their prevention. Left lung allotransplantation was performed in 6 weight-matched pigs (25-31 kg). Donor lungs were flushed with 1.5 L low-potassium dextran (LPD) solution (4 degrees C) and preserved for 20 h at 1 degrees C. One hour after reperfusion the recipient contralateral right lung was excluded from perfusion and ventilation to assess graft function only. Extravascular lung water index (EVLWI), intrathoracic blood volume (ITBV), and cardiac output (CO) were assessed (q = 30 min) with a lung water computer (Cold Z-021, Partig, Munich, Germany) by the thermo-dye technique during a 5-h observation period. Gas exchange (FIO2 = 1.0) was measured hourly, and hemodynamics were monitored continuously. The EVLWI of the recipient contralateral lung together with the donor left lung at the time of reperfusion was 6.5+/-1.1 ml/kg, increasing to 7.1+/-1.0 ml/kg at 60 min after reperfusion. After occlusion of the recipient right lung, EVLWI in the graft further increased within 80 min from 8.1+/-0.5 ml/kg to a peak of 11.4+/-1.3 ml/kg, followed by a decrease to 8.5+/-0.8 ml/kg at 5 h after reperfusion in 5 of 6 animals. In 1 animal a severe alveolar edema developed with subsequent deterioration of gas exchange and death 4.5 h after reperfusion. In this animal, peak EVLWI reached 16.8 ml/kg, PaO2 deteriorated from 60.1 to 7.8 kPa, and CO decreased from 3.1 to 1.4 L/min. In all other animals, ITBV (515+/-51 ml), left atrial pressure (LAP), central venous pressure (CVP), and CO (2.9+/-0.3 L/min) were stable during the 5-h assessment period. We conclude that EVLWI measurement is a reliable and very sensitive method to quantify lung allograft reperfusion edema. It may prove useful in early assessment of lung allograft reperfusion injury in the clinical setting and in experimental models.
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PMID:A new model for the assessment of lung allograft ischemia/reperfusion injury. 1074 52

Platelet-activating factor (PAF) is an important endogenous mediator of pulmonary edema in many models of acute lung injury. PAF triggers edema formation by simultaneous activation of two independent pathways; one is mediated by a cyclooxygenase metabolite, and the other is blocked by quinine. We examined the hypothesis that the cyclooxygenase-dependent part of PAF-induced edema is mediated by prostaglandin E(2) (PGE(2)). In isolated rat lungs, PAF administration stimulated release of PGE(2) into the venous effluate and increased lung weight as a measure of edema formation. Perfusion with a neutralizing PGE(2) antibody attenuated the PAF-induced edema formation. In vivo, E-prostanoid 3-receptor-deficient mice showed less pulmonary Evans blue extravasation in response to PAF injection than did mice deficient in EP1, EP2, or EP4 receptors. Perfusion of rat lungs with PGE(2) caused pulmonary edema, which was largely prevented by inhibition of voltage-gated potassium channels (25 nM beta-dendrotoxin), but not by blocking calcium-dependent potassium currents (100 micro M paxilline). In line with its effects on PGE(2)-induced edema formation, beta-dendrotoxin attenuated PAF-induced edema partly if given alone, and completely in combination with quinine. Our findings suggest that PAF-triggered edema is partly mediated by the release of PGE(2), activation of EP3 receptors, and activation of voltage-gated potassium channels.
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PMID:Platelet-activating factor-induced pulmonary edema is partly mediated by prostaglandin E(2), E-prostanoid 3-receptors, and potassium channels. 1220 61

Patch clamp methods were used to study the effect of lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, on voltage-dependent outward current of lung pericytes. Pericytes are located in capillary walls and may mediate pathological changes in microvascular hemodynamics and permeability that accompany endotoxin-mediated pulmonary edema. Previous studies have shown that LPS reduces lung pericyte contractility. Lung pericytes exhibited a voltage-dependent outward current, presumed to be K+ current, and this current increased in magnitude in response to LPS. Cells incubated for 48 hr without LPS (control) had an average peak current at 50 mV of 101 pA (n = 5 cells), whereas cells incubated with 100 mg/ml LPS had an average peak current of 927 pA (n = 9 cells, P<0.01 compared to control). When held at 50 mV for 50 msec, net outward current decreased in control cells by 10.7% and in LPS-treated cells by 2.6% (P<0.05). The increased activation of outward current in LPS-treated cells may be due to a previously inactive potassium channel and may mediate LPS-induced relaxation of the lung pericyte.
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PMID:Lipopolysaccharide (LPS) enhancement of outward current in lung pericytes. 1239 11

Pulmonary edema is the hallmark of acute respiratory distress syndrome. It occurs when the permeability of the alveolar-capillary barrier is increased, causing alveolar flooding and impaired gas exchange. The mechanisms of alveolar fluid resorption are different from those of alveolar edema formation. Alveolar fluid resorption into the vessels is brought about mainly by active transport of sodium ions (Na+) out of the alveolar spaces with water following the osmotic gradient. Na+ transport across the alveolar epithelium, and thus alveolar fluid resorption, is regulated by apical Na+ channels, the basolateral sodium potassium-adenosine triphosphatase (Na,K-ATPase), and possibly chloride channels. The Na,K-ATPase has been localized to the alveolar epithelium and the importance of its role in contributing to lung edema clearance has been demonstrated. In models of lung injury, several reports have shown that catecholamines such as isoproterenol and dopamine up-regulate Na+ channels and the Na,K-ATPase giving rise to increased alveolar fluid resorption. Although recombinant gene technology is not yet a therapeutic option for the treatment of pulmonary edema, several experimental studies have reported that overexpression of Na,K-ATPase genes causes increased fluid resorption during hyperoxic lung injury. There is significant evidence that fluid clearance is impaired in patients with lung injury. Therapeutic strategies aimed at increasing the ability of alveolar epithelium to resorb the edema should lead to benefits for patients with acute respiratory distress syndrome.
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PMID:Mechanisms of pulmonary edema clearance during acute hypoxemic respiratory failure: role of the Na,K-ATPase. 1268 48

To determine the impact of transplantation-associated injury on the clearance mechanisms of pulmonary edema, we created a canine single lung transplant model. After 3 hours of preservation and 4 hours of reperfusion, right native lungs and left transplanted lungs were used to measure alveolar liquid clearance (ALC) in ex vivo liquid-filled lung preparations. We also examined the role of the pulmonary circulation in edema clearance in in vivo liquid-filled lungs between 4 and 8 hours of reperfusion. To study molecular modifications in ALC, we also measured expression levels of the epithelial sodium channel (ENaC) and sodium-potassium-adenosine triphosphatase (ATPase). We found that ALC was significantly lower in transplanted than in right native lungs ex vivo (p < 0.05) and that transplanted lungs did not respond to the beta-adrenergic agonist terbutaline. Our in vivo study confirmed the ex vivo results. Molecular analyses revealed that ENaC messenger RNA but not sodium-potassium-ATPase was significantly decreased in transplanted lungs (p < 0.01). Furthermore, there was a significant decrease in ENaC protein expression. Therefore, we conclude that the current investigation indicates that the lung injury caused by lung preservation and transplantation significantly reduces the edema clearance ability of transplanted lungs.
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PMID:Alveolar liquid clearance and sodium channel expression are decreased in transplanted canine lungs. 1273 1

Sodium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Potassium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are inorganic salts that function as reducing agents in cosmetic formulations. All except Sodium Metabisulfite also function as hair-waving/straightening agents. In addition, Sodium Sulfite, Potassium Sulfite, Sodium Bisulfite, and Sodium Metabisulfite function as antioxidants. Although Ammonium Sulfite is not in current use, the others are widely used in hair care products. Sulfites that enter mammals via ingestion, inhalation, or injection are metabolized by sulfite oxidase to sulfate. In oral-dose animal toxicity studies, hyperplastic changes in the gastric mucosa were the most common findings at high doses. Ammonium Sulfite aerosol had an acute LC(50) of >400 mg/m(3) in guinea pigs. A single exposure to low concentrations of a Sodium Sulfite fine aerosol produced dose-related changes in the lung capacity parameters of guinea pigs. A 3-day exposure of rats to a Sodium Sulfite fine aerosol produced mild pulmonary edema and irritation of the tracheal epithelium. Severe epithelial changes were observed in dogs exposed for 290 days to 1 mg/m(3) of a Sodium Metabisulfite fine aerosol. These fine aerosols contained fine respirable particle sizes that are not found in cosmetic aerosols or pump sprays. None of the cosmetic product types, however, in which these ingredients are used are aerosolized. Sodium Bisulfite (tested at 38%) and Sodium Metabisulfite (undiluted) were not irritants to rabbits following occlusive exposures. Sodium Metabisulfite (tested at 50%) was irritating to guinea pigs following repeated exposure. In rats, Sodium Sulfite heptahydrate at large doses (up to 3.3 g/kg) produced fetal toxicity but not teratogenicity. Sodium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite were not teratogenic for mice, rats, hamsters, or rabbits at doses up to 160 mg/kg. Generally, Sodium Sulfite, Sodium Metabisulfite, and Potassium Metabisulfite were negative in mutagenicity studies. Sodium Bisulfite produced both positive and negative results. Clinical oral and ocular-exposure studies reported no adverse effects. Sodium Sulfite was not irritating or sensitizing in clinical tests. These ingredients, however, may produce positive reactions in dermatologic patients under patch test. In evaluating the positive genotoxicity data found with Sodium Bisulfite, the equilibrium chemistry of sulfurous acid, sulfur dioxide, bisulfite, sulfite, and metabisulfite was considered. This information, however, suggests that some bisulfite may have been present in genotoxicity tests involving the other ingredients and vice versa. On that basis, the genotoxicity data did not give a clear, consistent picture. In cosmetics, however, the bisulfite form is used at very low concentrations (0.03% to 0.7%) in most products except wave sets. In wave sets, the pH ranges from 8 to 9 where the sulfite form would predominate. Skin penetration would be low due to the highly charged nature of these particles and any sulfite that did penetrate would be converted to sulfate by the enzyme sulfate oxidase. As used in cosmetics, therefore, these ingredients would not present a genotoxicity risk. The Cosmetic Ingredient Review Expert Panel concluded that Sodium Sulfite, Potassium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are safe as used in cosmetic formulations.
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PMID:Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite. 1455 20

Chronic hypoxia results in both structural changes in the pulmonary artery and a sustained increase in pulmonary vascular tone. This study investigated the effects of subacute moderate hypoxia on expression and function of potassium (K+) channels in rat pulmonary artery myocytes (PASMCs). The rats were kept at 0.67 atmospheres for 6, 12, or 24 h. We found that the expression of mRNA for voltage-activated K+ channels (Kv)1.2, Kv1.5, and Kv2.1 is reduced after less than 24 h of this moderate hypoxia. K+ current (Ik) is significantly inhibited in PASMCs from rats hypoxic for 24 h, resting membrane potential is depolarized and cytosolic [Ca2+] is increased in these cells. In addition, antibodies to Kv1.2, Kv1.5, and Kv2.1 inhibit Ik, cause membrane depolarization and attenuate both hypoxia- and 4-AP-induced elevation in [Ca2+]i in PASMCs from normoxic rats but not from 24 h hypoxic rats. Subacute hypoxia does not completely remove the mRNA for Kv1.2, Kv1.5, and Kv2.1, but antibodies against these channels no longer alter Ik or cytosolic calcium, suggesting that subacute hypoxia may inactivate the channels as well as reduce expression. As the expression of mRNA for Kv1.2, Kv1.5, and Kv2.1 is sensitive to subacute hypoxia and decreased expression/function of these channels has physiologic effects on membrane potential and cytosolic calcium, it seems likely that these Kv channels may also be involved in the mechanism of high-altitude pulmonary edema and possibly in the signaling of chronic hypoxic pulmonary hypertension.
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PMID:Subacute hypoxia decreases voltage-activated potassium channel expression and function in pulmonary artery myocytes. 1515 18

To determine the effects of Tityus serrulatus scorpion toxin on lung compliance and resistance, ionic equilibrium and acid-base balance over time in anesthetized and mechanically ventilated rats, we measured air flow, tracheal and esophageal pressure. Lung volume was obtained by electronic integration of airflow signal. Arterial blood samples were collected through a catheter at baseline (before) and 5, 15, 30 and 60 min after scorpion toxin injection for arterial blood gases, bicarbonate, and alkali reserve levels as well as for, sodium, potassium, magnesium, glucose, lactate, hematocrit, and osmolality analysis. Injection of the gamma fraction of the T. serrulatus scorpion venom in rats under mechanical ventilatory support leads to a continuous decrease in lung compliance secondary to pulmonary edema, but no change in airway resistance. The changes in arterial blood gases characterizing metabolic acidosis were accompanied by an increase in arterial lactate and glucose values, suggesting a scorpion toxin-induced lactic acidosis, in association with poor tissue perfusion (hypotension and low cardiac output). Moreover, scorpion toxin injection resulted in hyperosmolality, hyperkalemia, hypermagnesemia and an increase in hematocrit. The experiments have shown a clinically relevant animal model to study severe scorpion envenoming and may help to better understand the scorpion envenoming syndrome.
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PMID:Lung compliance, plasma electrolyte levels and acid-base balance are affected by scorpion envenomation in anesthetized rats under mechanical ventilation. 1531 52

Humans encounter hypoxia throughout their lives. This occurs by destiny in utero, through disease, and by desire, in our quest for altitude. Hypoxic pulmonary vasoconstriction (HPV) is a widely conserved, homeostatic, vasomotor response of resistance pulmonary arteries to alveolar hypoxia. HPV mediates ventilation-perfusion matching and, by reducing shunt fraction, optimizes systemic Po(2). HPV is intrinsic to the lung, and, although modulated by the endothelium, the core mechanism is in the smooth muscle cell (SMC). The Redox Theory for the mechanism of HPV proposes the coordinated action of a redox sensor (the proximal mitochondrial electron transport chain) that generates a diffusible mediator [a reactive O(2) species (ROS)] that regulates an effector protein [voltage-gated potassium (K(v)) and calcium channels]. A similar mechanism for regulating O(2) uptake/distribution is partially recapitulated in simpler organisms and in the other specialized mammalian O(2)-sensitive tissues, including the carotid body and ductus arteriosus. Inhibition of O(2)-sensitive K(v) channels, particularly K(v)1.5 and K(v)2.1, depolarizes pulmonary artery SMCs, activating voltage-gated Ca(2+) channels and causing Ca(2+) influx and vasoconstriction. Downstream of this pathway, there is important regulation of the contractile apparatus' sensitivity to calcium by rho kinase. Controversy remains as to whether hypoxia decreases or increases ROS and which electron transport chain complex generates the ROS (I and/or III). Possible roles for cyclic adenosine diphosphate ribose and an unidentified endothelial constricting factor are also proposed by some groups. Modulation of HPV has therapeutic relevance to cor pulmonale, high-altitude pulmonary edema, and sleep apnea. HPV is clinically exploited in single-lung anesthesia, and its mechanisms intersect with those of pulmonary arterial hypertension.
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PMID:Hypoxic pulmonary vasoconstriction. 1559 9


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