scholarly journals Physiological and biochemical markers of alveolar epithelial barrier dysfunction in perfused human lungs

2007 ◽  
Vol 293 (1) ◽  
pp. L52-L59 ◽  
Author(s):  
James A. Frank ◽  
Raphael Briot ◽  
Jae Woo Lee ◽  
Akitoshi Ishizaka ◽  
Tokujiro Uchida ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Fluid Balance ◽  
Human Lung ◽  
Biological Marker ◽  
Epithelial Injury ◽  
Alveolar Epithelial ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Human Lungs ◽  
Air Space

To study air space fluid clearance (AFC) under conditions that resemble the clinical setting of pulmonary edema in patients, we developed a new perfused human lung preparation. We measured AFC in 20 human lungs rejected for transplantation and determined the contribution of AFC to lung fluid balance. AFC was then compared with air space and perfusate levels of a biological marker of epithelial injury. The majority of human lungs rejected for transplant had intact basal (75%) and β2-adrenergic agonist-stimulated (70%) AFC. For lungs with both basal and stimulated AFC, the basal AFC rate was 19 ± 10%/h, and the β2-adrenergic-stimulated AFC rate was 43 ± 13%/h. Higher rates of AFC were associated with less lung weight gain (Pearson coefficient −0.90, P < 0.0001). Air space and perfusate levels of the type I pneumocyte marker receptor for advanced glycation end products (RAGE) were threefold and sixfold higher, respectively, in lungs without basal AFC compared with lungs with AFC ( P < 0.05). These data show that preserved AFC is a critical determinant of favorable lung fluid balance in the perfused human lung, raising the possibility that β2-agonist therapy to increase edema fluid clearance may be of value for patients with acute lung injury and pulmonary edema. Also, although additional studies are needed, a biological marker of alveolar epithelial injury may be useful clinically in predicting preserved AFC.

Oleic acid lung injury in sheep

1986 ◽  
Vol 60 (2) ◽  
pp. 433-440 ◽  
Author(s):  
M. Julien ◽  
J. M. Hoeffel ◽  
M. R. Flick
Keyword(s):  
Oleic Acid ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Fluid Balance ◽  
Lymph Flow ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Lung Lymph Flow

Intravenous infusion of oleic acid into experimental animals causes acute lung injury resulting in pulmonary edema. We investigated the mechanism of oleic acid lung injury in sheep. In experiments with anesthetized and unanesthetized sheep with lung lymph fistulas, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and lymph and plasma protein concentrations. We injured the lungs with intravenous infusions of oleic acid at doses ranging from 0.015 to 0.120 ml/kg. We found that oleic acid caused reproducible dose-related increases in pulmonary arterial pressure and pulmonary vascular resistance, arterial hypoxemia, and increased protein-rich lung lymph flow and extravascular lung water. The lung fluid balance changes were characteristic of increased permeability pulmonary edema. Infusion of the esterified fat triolein had no hemodynamic or lung fluid balance effects. Depletion of leukocytes with a nitrogen mustard or platelets with an antiplatelet serum had no effect on oleic acid lung injury. Treatment of sheep before injury with methylprednisolone 30 mg/kg or ibuprofen 12.5–15.0 mg/kg also had no effects. Unlike other well-characterized sheep lung injuries, injury caused by oleic acid does not require participation of leukocytes.

scholarly journals Nadph oxidase regulates alveolar epithelial sodium channel activity and lung fluid balance in vivo via O2− signaling

2012 ◽  
Vol 302 (4) ◽  
pp. L410-L419 ◽  
Author(s):  
Preston Goodson ◽  
Amrita Kumar ◽  
Lucky Jain ◽  
Kousik Kundu ◽  
Niren Murthy ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Sodium Channel ◽  
Fluid Balance ◽  
Epithelial Sodium Channel ◽  
Ros Production ◽  
Open Probability ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Air Space

To define roles for reactive oxygen species (ROS) and epithelial sodium channel (ENaC) in maintaining lung fluid balance in vivo, we used two novel whole animal imaging approaches. Live X-ray fluoroscopy enabled quantification of air space fluid content of C57BL/6J mouse lungs challenged by intratracheal (IT) instillation of saline; results were confirmed by using conventional lung wet-to-dry weight ratios and Evans blue as measures of pulmonary edema. Visualization and quantification of ROS produced in lungs was performed in mice that had been administered a redox-sensitive dye, hydro-Cy7, by IT instillation. We found that inhibition of NADPH oxidase with a Rac-1 inhibitor, NSC23766, resulted in alveolar flooding, which correlated with a decrease in lung ROS production in vivo. Consistent with a role for Nox2 in alveolar fluid balance, Nox2−/− mice showed increased retention of air space fluid compared with wild-type controls. Interestingly, fluoroscopic analysis of C57BL/6J lungs IT instilled with LPS showed an acute stimulation of lung fluid clearance and ROS production in vivo that was abrogated by the ROS scavenger tetramethylpiperidine- N-oxyl (TEMPO). Acute application of LPS increased the activity of 20 pS nonselective ENaC channels in rat type 1 cells; the average number of channel and single-channel open probability ( NPo) increased from 0.14 ± 0.04 to 0.62 ± 0.23. Application of TEMPO to the same cell-attached recording caused an immediate significant decrease in ENaC NPo to 0.04 ± 0.03. These data demonstrate that, in vivo, ROS has the capacity to stimulate lung fluid clearance by increasing ENaC activity.

Equivalent pore estimate for the alveolar-airway barrier in isolated dog lung

1988 ◽  
Vol 64 (3) ◽  
pp. 1134-1142 ◽  
Author(s):  
R. L. Conhaim ◽  
A. Eaton ◽  
N. C. Staub ◽  
T. D. Heath
Keyword(s):  
High Pressure ◽  
Pulmonary Edema ◽  
Intercellular Junctions ◽  
Model Fit ◽  
Epithelial Injury ◽  
Pore Model ◽  
Liquid Flux ◽  
Air Space ◽  
Lung Lobes

In high-pressure pulmonary edema, lung interstitial and air space edema liquids have equal protein concentrations (Am. J. Physiol. 231: 1466, 1976). This suggests that the alveolar-airway barrier separating the air and interstitial spaces is relatively unrestrictive, even without apparent epithelial injury. To estimate the equivalent pore population of the alveolar-airway barrier we inflated each of 18 isolated dog lung lobes for 1 h with a solution of colored tracer of uniform radius. Tracer radii ranged from 1.3 to 405 nm. After freezing the lobes in liquid N2, we measured interstitial tracer concentrations in frozen perivascular cuffs or in samples thawed after dissection from frozen cuffs. Relative to the concentrations instilled, interstitial concentrations ranged from 0.34 for the smallest particles (1.3 and 3.5 nm radius) to zero for particles with radii of 405 nm. From the results we designed a pore model of the alveolar-airway barrier to reproduce the concentrations we measured. No single-pore model could be obtained, although a three-pore model fit the data well. The model results predict that pores with radii of 1, 40, and 400 nm would account for 68, 30, and 2% of total liquid flux, respectively. The majority of liquid flux (68%) would occur through passageways smaller than the smallest tracer we used (1.3 nm radius). We believe the alveolar-airway barrier consists not only of tight intercellular junctions that allow passage of only water and electrolytes but also of a smaller number of large leaks that allow passage of particles up to nearly 400 nm in radius.

scholarly journals Lung fluid balance in patients with heart failure: effect of beta‐2 adrenergic‐receptor stimulation

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Bryan Taylor ◽  
Maile Ceridon ◽  
Eric Snyder ◽  
Alex Carlson ◽  
Minelle Hulsebus ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fluid Balance ◽  
Adrenergic Receptor ◽  
Receptor Stimulation ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Patients With Heart Failure ◽  
Beta 2

Sodium transport and fluid balance in lungs from normal and dystrophic hamsters

1994 ◽  
Vol 77 (4) ◽  
pp. 1750-1754 ◽  
Author(s):  
W. F. Waltz ◽  
J. A. Burbach ◽  
E. H. Schlenker ◽  
B. E. Goodman
Keyword(s):  
Fluid Balance ◽  
Sodium Transport ◽  
Fluorescein Isothiocyanate ◽  
Dry Weight ◽  
Apparent Permeability ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Permeability Surface ◽  
Lower Permeability ◽  
Sodium Clearance

Gravimetric and sodium transport characteristics of lungs from BIO 14.6 (dystrophic) hamsters were compared with those of lungs from golden Syrian (normal) hamsters at 30 and 150 days of age. Isolated perfused lungs were used to determine lung permeability and fluid balance differences between normal and dystrophic animals at both ages. Apparent permeability-surface area products for air space-to-vascular space sodium, sucrose, and fluorescein isothiocyanate-labeled dextran fluxes were compared in the four groups of hamsters. Morphometric analysis of fixed lungs of representative hamsters from each group was also performed. Dystrophic hamsters exhibited higher lung wet-to-dry weight ratios than normal hamsters at both ages. Lungs from dystrophic hamsters were less sensitive to inhibition of sodium transport by amiloride than lungs from age-matched normal hamsters. Dystrophic hamster lungs had higher absolute permeabilities of the passively transported solutes, lower permeability values for sodium, and only one-half of the amiloride-sensitive sodium transport of lungs from age-matched normal hamsters. Differences in lung fluid balance between dystrophic and normal hamsters may be related to differences in sodium clearance.

Inspiratory airway obstruction does not affect lung fluid balance in lambs

1985 ◽  
Vol 58 (4) ◽  
pp. 1314-1318 ◽  
Author(s):  
T. N. Hansen ◽  
A. L. Gest ◽  
S. Landers
Keyword(s):  
Airway Obstruction ◽  
Endotracheal Tube ◽  
Fluid Balance ◽  
Left Atrial ◽  
Lymph Flow ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Lung Lymph Flow

The purpose of this study was to examine the effects of inspiratory airway obstruction on lung fluid balance in newborn lambs. We studied seven 2- to 4-wk-old lambs that were sedated with chloral hydrate and allowed to breathe 30–40% O2 spontaneously through an endotracheal tube. We measured lung lymph flow, lymph and plasma protein concentrations, pulmonary arterial and left atrial pressures, mean and phasic pleural pressures and airway pressures, and cardiac output during a 2-h base-line period and then during a 2- to 3-h period of inspiratory airway obstruction produced by partially occluding the inspiratory limb of a nonrebreathing valve attached to the endotracheal tube. During inspiratory airway obstruction, both pleural and airway pressures decreased 5 Torr, whereas pulmonary arterial and left atrial pressures each decreased 4 Torr. As a result, calculated filtration pressure remained unchanged. Inspiratory airway obstruction had no effect on steady-state lung lymph flow or the lymph protein concentration relative to that of plasma. We conclude that in the spontaneously breathing lamb, any decrease in interstitial pressure resulting from inspiratory airway obstruction is offset by a decrease in microvascular hydrostatic pressure so that net fluid filtration remains unchanged.

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