Invited Review: Alveolar edema fluid clearance in the injured lung

2002 ◽  
Vol 93 (6) ◽  
pp. 2207-2213 ◽  
Author(s):  
Yves Berthiaume ◽  
Hans G. Folkesson ◽  
Michael A. Matthay
Keyword(s):  
Lung Injury ◽  
Sodium Transport ◽  
Molecular Mechanisms ◽  
Chloride Transport ◽  
Edema Fluid ◽  
Injured Lung ◽  
Transport Molecules ◽  
Alveolar Liquid Clearance ◽  
Alveolar Edema ◽  
Alveolar Liquid

Resolution of pulmonary edema involved active transepithelial sodium transport. Although several of the cellular and molecular mechanisms involved are relatively well understood, it is only recently that the regulation of these mechanisms in injured lung are being evaluated. Interestingly, in mild-to-moderate lung injury, alveolar edema fluid clearance is often preserved. This preserved or enhanced alveolar fluid clearance is mediated by catecholamine-dependent or -independent mechanisms. This stimulation of alveolar liquid clearance is related to activation or increased expression of sodium transport molecules such as the epithelial sodium channel or the Na+-K+-ATPase pump and may also involve the cystic fibrosis transmembrane conductance regulator. When severe lung injury occurs, the decrease in alveolar liquid clearance may be related to changes in alveolar permeability or to changes in activity or expression of sodium or chloride transport molecules. Multiple pharmacological tools such as β-adrenergic agonists, vasoactive drugs, or gene therapy may prove effective in stimulating the resolution of alveolar edema in the injured lung.

scholarly journals Alveolar edema fluid clearance and acute lung injury

2007 ◽  
Vol 159 (3) ◽  
pp. 350-359 ◽  
Author(s):  
Yves Berthiaume ◽  
Michael A. Matthay
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Edema Fluid ◽  
Alveolar Edema

Effect of epinephrine on alveolar liquid clearance in the rat

1999 ◽  
Vol 87 (2) ◽  
pp. 611-618 ◽  
Author(s):  
Paul D. Charron ◽  
J. Phillip Fawley ◽  
Michael B. Maron
Keyword(s):  
Pulmonary Edema ◽  
Mass Balance ◽  
Sodium Transport ◽  
No Reduction ◽  
Plasma Epinephrine ◽  
Epinephrine Infusion ◽  
Baseline Values ◽  
Alveolar Liquid Clearance ◽  
Epinephrine Concentration ◽  
Alveolar Liquid

Endogenous epinephrine has been found to increase alveolar liquid clearance (ALC) in several pulmonary edema models. In this study, we infused epinephrine intravenously for 1 h in anesthetized rats to produce plasma epinephrine concentrations commonly observed in this species under stressful conditions and measured ALC by mass balance. Epinephrine increased ALC from 31.5 ± 3.2 to 48.9 ± 1.1 (SE)% of the instilled volume ( P < 0.05). The increased ALC was prevented by either propranolol or amiloride. To determine whether ALC returns to normal after plasma epinephrine concentration normalizes, we measured ALC 2 h after stopping an initial 1-h epinephrine infusion and found ALC to be at baseline values. Finally, to determine whether desensitization of the liquid clearance response occurs, we evaluated the effects of both repeated 1-h infusions and a continuous 4-h infusion of epinephrine on ALC and found no reduction in ALC under either condition. We conclude that epinephrine increases ALC by stimulating β-adrenoceptors and sodium transport, that the increase is reversible once plasma epinephrine concentration normalizes, and that desensitization of the ALC response does not appear to occur after 4 h of continuous epinephrine exposure.

Increased leukotriene C4 in ethchlorvynol-induced acute lung injury in dogs

1987 ◽  
Vol 62 (2) ◽  
pp. 732-738 ◽  
Author(s):  
A. H. Stephenson ◽  
R. S. Sprague ◽  
T. E. Dahms ◽  
A. J. Lonigro
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Leukotriene C4 ◽  
Lung Water ◽  
Control Value ◽  
Edema Fluid ◽  
Injured Lung ◽  
Anesthetized Dogs ◽  
Arterial Plasma

We investigated whether ethchlorvynol (ECV)-induced acute lung injury (ALI) is associated with an increase in leukotriene C4 (LTC4) production. In six pentobarbital sodium-anesthetized dogs, ECV (15 mg/kg iv) introduced into the pulmonary circulation resulted in a 164 +/- 31% increase in extravascular lung water 120 min after ECV administration. Concomitantly, the mean (+/- SE) concentration of LTC4 in arterial plasma measured by radioimmunoassay following 80% EtOH precipitation, XAD-7 extraction and high-pressure liquid chromatography purification was 5.0 +/- 1.3 pg/ml, unchanged from control (pre-ECV) values. In contrast, in pulmonary edema fluid 120 min post-ECV, the LTC4 concentration was 35.2 +/- 10.8 pg/ml, sevenfold greater than those values found in the arterial plasma (P less than 0.01). In six additional dogs, 120 min after unilateral ALI had been induced with ECV (9 mg/kg iv), LTC4 in the bronchoalveolar lavage (BAL) of the uninjured lung was 12.1 +/- 1.5 pg/ml, unchanged from pre-ECV values, whereas, LTC4 in the BAL of the injured lung increased from a control value of 10.2 +/- 1.6 to 24.2 +/- 3.5 pg/ml (P less than 0.01) 120 min after ECV administration. These results demonstrate that, in ECV-induced acute lung injury, LTC4 concentrations in pulmonary edema fluid are considerably greater than those found in arterial plasma in the case of bilateral acute lung injury and significantly greater in the BAL of the injured lung compared with the uninjured lung in the case of unilateral acute lung injury. The results are a necessary first step in support of the hypothesis that leukotrienes participate in the altered permeability of ECV-induced acute lung injury.

Terbutaline stimulates alveolar fluid resorption in hyperoxic lung injury

1996 ◽  
Vol 81 (4) ◽  
pp. 1723-1729 ◽  
Author(s):  
Joseph M. Lasnier ◽  
O. Douglas Wangensteen ◽  
Laura S. Schmitz ◽  
Cynthia R. Gross ◽  
David H. Ingbar
Keyword(s):  
Lung Injury ◽  
Sodium Transport ◽  
Ringer Solution ◽  
Lung Weight ◽  
Rat Lungs ◽  
Steady State Rate ◽  
Absolute Effect ◽  
Hyperoxic Lung Injury ◽  
State Rate ◽  
Alveolar Edema

Lasnier, Joseph M., O. Douglas Wangensteen, Laura S. Schmitz, Cynthia R. Gross, and David H. Ingbar. Terbutaline stimulates alveolar fluid resorption in hyperoxic lung injury. J. Appl. Physiol. 81(4): 1723–1729, 1996.—Alveolar fluid resorption occurs by active epithelial sodium transport and is accelerated by terbutaline in healthy lungs. We investigated the effect of terbutaline on the rate of alveolar fluid resorption from rat lungs injured by hyperoxia. Rats exposed to >95% O2 for 60 h, sufficient to increase wet-to-dry lung weight and cause alveolar edema, were compared with air-breathing control rats. After anesthesia, the animals breathed 100% O2 for 10 min through a tracheostomy. Ringer solution was instilled into the alveoli, and the steady-state rate of volume resorbed at 6 cmH2O pressure was measured via a pipette attached to the tracheostomy tubing. Ringer solution in some animals contained terbutaline (10−3 M), ouabain (10−3 M), or both. Normoxic animals resorbed 49 ± 6 μl ⋅ kg−1 ⋅ min−1; ouabain reduced this by 39%, whereas terbutaline increased the rate by 75%. The effect of terbutaline was blocked by ouabain. Hyperoxic animals absorbed 78 ± 9 μl ⋅ kg−1 ⋅ min−1; ouabain reduced this by 44%. Terbutaline increased the rate by a mean of 39 μl ⋅ kg−1 ⋅ min−1, similar to the absolute effect seen in the normoxic group, and this was blocked by ouabain. Terbutaline accelerates fluid resorption from both normal and injured rat lungs via its effects on active sodium transport.

scholarly journals Protein expression profile of rat type two alveolar epithelial cells during hyperoxic stress and recovery

2013 ◽  
Vol 305 (9) ◽  
pp. L604-L614 ◽  
Author(s):  
Maneesh Bhargava ◽  
Sanjoy Dey ◽  
Trisha Becker ◽  
Michael Steinbach ◽  
Baolin Wu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Model Systems ◽  
Regulatory Pathways ◽  
Lung Repair ◽  
Injured Lung

In rodent model systems, the sequential changes in lung morphology resulting from hyperoxic injury are well characterized and are similar to changes in human acute respiratory distress syndrome. In the injured lung, alveolar type two (AT2) epithelial cells play a critical role in restoring the normal alveolar structure. Thus characterizing the changes in AT2 cells will provide insights into the mechanisms underpinning the recovery from lung injury. We applied an unbiased systems-level proteomics approach to elucidate molecular mechanisms contributing to lung repair in a rat hyperoxic lung injury model. AT2 cells were isolated from rat lungs at predetermined intervals during hyperoxic injury and recovery. Protein expression profiles were determined by using iTRAQ with tandem mass spectrometry. Of the 959 distinct proteins identified, 183 significantly changed in abundance during the injury-recovery cycle. Gene ontology enrichment analysis identified cell cycle, cell differentiation, cell metabolism, ion homeostasis, programmed cell death, ubiquitination, and cell migration to be significantly enriched by these proteins. Gene set enrichment analysis of data acquired during lung repair revealed differential expression of gene sets that control multicellular organismal development, systems development, organ development, and chemical homeostasis. More detailed analysis identified activity in two regulatory pathways, JNK and miR 374. A novel short time-series expression miner algorithm identified protein clusters with coherent changes during injury and repair. We concluded that coherent changes occur in the AT2 cell proteome in response to hyperoxic stress. These findings offer guidance regarding the specific molecular mechanisms governing repair of the injured lung.

Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

2020 ◽  
Vol 16 (1) ◽  
pp. 85-89
Author(s):  
Mahesh M. Gouda ◽  
Ashwini Prabhu ◽  
Varsha Reddy S.V. ◽  
Rafa Jahan ◽  
Yashodhar P. Bhandary
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Plasminogen Activator Inhibitor ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Alveolar Epithelial Cells ◽  
Cellular Damage

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

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