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

Inhaled nitric oxide (NO) may modify surfactant either by interacting with the surfactant complex or by changing the capacity of the proteins of the epithelial lining fluid to inhibit the surface activity. Natural surfactant was exposed to NO (80 parts/million) in air in vitro while the gas-liquid surface was cycled. In the presence or absence of oxidants (Fe2+, xanthine, xanthine oxidase), surfactant exposed to NO retained the high surface activity significantly better than control surfactants exposed to air. Two surfactant inhibitors, hemoglobin (Hb) and albumin, were separately exposed to NO. In contrast to albumin, NO-exposed Hb and methemoglobin (MetHb; 16-125 micrograms/ml) decreased the surface activity at low surfactant concentrations, whereas native Hb had no effect. Surfactant recovered by sedimentation after exposure to MetHb had decreased surface activity and contained MetHb, whereas Hb did not bind to surfactant. Acidic phospholipid phosphatidylglycerol increased the binding of MetHb to surfactant. The MetHb-induced decrease in surface activity was elicited in the presence of surfactant proteins, including a peptide mimicking surfactant protein B. MetHb (but not Hb) added to a low dose of exogenous surfactant decreased the efficacy of surfactant to improve the lung compliance of premature rabbits. We propose that inhaled NO promotes the surface activity of surfactant during tidal ventilation and that, in high-permeability lung edema and surfactant deficiency, inhaled NO increases the inhibition of surface activity by converting Hb to MetHb in the alveolar space.
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PMID:A mechanism of nitric oxide-induced surfactant dysfunction. 880 11

Phosgene exposure via an industrial or warfare release produces severe acute lung injury (ALI) with high mortality, characterized by massive pulmonary edema, disruption of epithelial tight junctions, surfactant dysfunction, and oxidative stress. There are no targeted treatments for phosgene-induced ALI. Previous studies demonstrated that nitric oxide synthase 2 (NOS-2) is upregulated in the lungs after phosgene exposure; however, the role of NOS-2 in the pathogenesis of phosgene-induced ALI remains unknown. We previously demonstrated that NOS-2 expression in lung epithelium exacerbates inhaled endotoxin-induced ALI in mice, mediated partially through downregulation of surfactant protein B (SP-B) expression. Therefore, we hypothesized that a selective NOS-2 inhibitor delivered to the lung epithelium by inhalation would mitigate phosgene-induced ALI. Inhaled phosgene produced increases in bronchoalveolar lavage fluid protein, histologic lung injury, and lung NOS-2 expression at 24 h. Administration of the selective NOS-2 inhibitor 1400 W via inhalation, but not via systemic delivery, significantly attenuated phosgene-induced ALI and preserved epithelial barrier integrity. Furthermore, aerosolized 1400 W augmented expression of SP-B and prevented downregulation of tight junction protein zonula occludens 1 (ZO-1), both critical for maintenance of normal lung physiology and barrier integrity. We also demonstrate for the first time that NOS-2-derived nitric oxide downregulates the ZO-1 expression at the transcriptional level in human lung epithelial cells, providing a novel target for ameliorating vascular leak in ALI. Our data demonstrate that lung NOS-2 plays a critical role in the development of phosgene-induced ALI and suggest that aerosolized NOS-2 inhibitors offer a novel therapeutic strategy for its treatment.
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PMID:NOS-2 Inhibition in Phosgene-Induced Acute Lung Injury. 2587 Mar 19

The conventional analysis of acute cardiogenic pulmonary edema involves the development of high pulmonary capillary pressures resulting in hydrostatic gradients for fluid flux out of capillaries into the interstitial space and alveolar spaces. However, some patients respond poorly to diuretic management. The PubMed database was searched to identify experimental studies on pulmonary edema in animals, experimental studies on surfactant function, including patients with pulmonary edema, and clinical studies reporting barrier dysfunction and/or injury in patients with acute pulmonary edema. Studies with animal models demonstrate that high capillary pressures can cause barrier disruption in alveolar capillary units which increases permeability and the transfer of fluid and protein into lung parenchyma. Fluid in alveolar spaces alters surfactant function which increases fluid flux out of capillaries into the lung parenchyma secondary to larger transcapillary hydrostatic gradients. Patients with acute cardiogenic pulmonary edema have increased levels of surfactant protein B in their plasma which reflect barrier disruption and increased levels of tumor necrosis factor alpha which reflect acute tissue injury. Increased surfactant protein B plasma levels are associated with abnormal gas exchange in patients with chronic heart failure. Patients with exercise-induced left ventricular dysfunction have increased levels of surfactant protein B after short periods of exercise. Pathology studies in patients with chronic heart failure have found increased connective tissue in alveolar capillary units and increased numbers of type II alveolar cells, and these changes represent an adaptive response in these patients. Clinicians need to consider the possibility of barrier dysfunction and disruption in patients with both acute and chronic pulmonary edema and understand that diuresis may have a limited effect on symptoms in some patients.
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PMID:Lung morphology and surfactant function in cardiogenic pulmonary edema: a narrative review. 3165 79

The initial events in cardiogenic pulmonary edema involve hemodynamic pulmonary congestion with high capillary pressures. This causes increased fluid transfer out of capillaries into the interstitium and alveolar spaces. High capillary pressures can also cause barrier disruption which increases permeability and fluid transfer into the interstitium and alveoli. Fluid in alveoli alters surfactant function and increases surface tension. This can lead to more edema formation and to atelectasis with impaired gas exchange. Patients with barrier disruption have increased levels of surfactant protein B in the circulation, and these levels often remain high after the initial clinical improvement. Routine clinical assessment may not identify patients with increased extravascular fluid in the lungs; pulmonary ultrasound can easily detect pulmonary edema in patients with acute decompensation and in patients at risk for decompensation. Studies using serial pulmonary ultrasound could help characterize patients with cardiogenic pulmonary edema and help identify subgroups who need alternative management. The conventional management of cardiogenic pulmonary edema usually involves diuresis, afterload reduction and in some cases noninvasive ventilation to reduce the work of breathing and improve oxygenation. Patients with persistent symptoms, abnormal chest x-rays and diuretic resistance might benefit from alternative approaches to management. These could include beta agonists and pentoxifylline which warrant more study in patients with cardiogenic pulmonary edema.
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PMID:Cardiogenic Pulmonary Edema. 3181 66