1 Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611; and 2 Departamento de Enfermedades Respiratorias, Pontificia Universidad Católica de Chile, Santiago, Chile
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Short-term mechanical ventilation with
high tidal volume (HVT) causes mild to moderate lung injury and impairs
active Na+ transport and lung liquid clearance in rats.
Dopamine (DA) enhances active Na+ transport in normal rat
lungs by increasing Na+-K+-ATPase activity in
the alveolar epithelium. We examined whether DA would increase alveolar
fluid reabsorption in rats ventilated with HVT for 40 min compared with
those ventilated with low tidal volume (LVT) and with nonventilated
rats. Similar to previous reports, HVT ventilation decreased alveolar
fluid reabsorption by ~50% (P < 0.001). DA
increased alveolar fluid reabsorption in nonventilated control rats (by
~60%), LVT ventilated rats (by ~55%), and HVT ventilated rats (by
~200%). In parallel studies, DA increased
Na+-K+-ATPase activity in cultured rat alveolar
epithelial type II cells (ATII). Depolymerization of cellular
microtubules by colchicine inhibited the effect of DA on HVT ventilated
rats as well as on Na+-K+-ATPase activity in
ATII cells. Neither DA nor colchicine affected the short-term
Na+-K+-ATPase 1- and
1-subunit mRNA steady-state levels or total
1- and
1-subunit protein abundance in
ATII cells. Thus we reason that DA improved alveolar fluid reabsorption
in rats ventilated with HVT by upregulating the
Na+-K+-ATPase function in alveolar epithelial cells.
Na+-K+-ATPase; alveolar fluid clearance
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
PULMONARY EDEMA FORMATION results from changes in hydrostatic or colloid-osmotic pressure gradients in the pulmonary circulation and/or increased alveolo-capillary barrier permeability (28). Patients with respiratory failure and pulmonary edema frequently need to be placed on mechanical ventilation. However, mechanical ventilation with high tidal volumes (HVT) may adversely affect lung function and cause or worsen lung injury (7, 9-11, 29-31). It has been reported that mechanical ventilation may cause physiological and morphological alterations similar to the diffuse alveolar damage observed in the acute respiratory distress syndrome (1, 10, 15, 19, 29, 32). Pulmonary edema resolution depends on active Na+ transport across the alveolar epithelium (14, 18, 26).
We previously reported that mechanical ventilation with HVT in rats decreased active Na+ transport and lung liquid clearance (17). Recently it was reported that dopamine (DA) placed in rat lung air spaces and/or pulmonary circulation increased active Na+ transport within 1 h in healthy rat lungs and Na+-K+-ATPase activity in alveolar epithelial cells within 15 min (2, 3, 16, 21). The purpose of this study was to determine the effects of DA on lung liquid clearance in mechanically ventilated rats.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
A total of 132 rat lungs were studied. Pathogen-free, male
Sprague-Dawley rats weighing 280-320 g were purchased from Harlan Sprague Dawley (Indianapolis, IN). All animals were provided food and
water ad libitum and maintained on a 12:12-h light-dark cycle. DA,
amiloride, ouabain, colchicine, and -lumicolchicine were purchased
from Sigma (St. Louis, MO).
Mechanical Ventilation
Adult rats were anesthetized with 50 mg of pentobarbital/kg body wt (BW) intraperitoneally, tracheotomized, and mechanically ventilated with a rodent ventilator (model 683; Harvard Apparatus, South Natick, MA). The animals were ventilated for 40 min with HVT of ~40 ml/kg, peak airway pressure of 35 cmH2O, and respiratory rate (RR) of 40 breath/min without positive end-expiratory pressure and compared with rats ventilated with low tidal volume (LVT) for 40 min (~10 ml/kg; peak airway pressure, 8 cmH2O; RR, 40 breath/min) and control nonventilated rats. It has been previously reported that HVT ventilation to 35 cmH2O for 40 min causes mild to moderate lung injury and decreases alveolar epithelial fluid reabsorption in rats (17, 23).Specific Protocols
Group A. Lung liquid clearance was measured in a control nonventilated group of rats instilled with 5 ml of buffered salt albumin (BSA) solution into the air spaces (n = 10).
Group B. Lung liquid clearance was measured in rats ventilated with LVT for 40 min and instilled with 5 ml of BSA solution into the air spaces (n = 6).
Group C. Lung liquid clearance was measured in rats ventilated with HVT for 40 min and instilled with 5 ml of BSA solution into the air spaces (n = 6).
Group D.
To examine lung liquid clearance modulation by DA, we instilled
104 M DA into the air space of three groups of animals:
HVT (n = 6) and LVT (n = 6) ventilated
for 40 min and control nonventilated rats (n = 8).
Group E.
To study the role of epithelial Na+ transport on lung
liquid clearance modulation by DA in control rats, we studied the
effect of 1) the Na+ channel blocker amiloride
(104 M) instilled into control rat air spaces with
10
4 M DA (n = 5) and without DA
(n = 6), and 2) the
Na+-K+-ATPase inhibitor ouabain (5 × 10
4 M) perfused through the pulmonary circulation in rats
treated with 10
4 M DA (n = 5) or without
DA (n = 6).
Group F.
To study the role of epithelial Na+ transport on lung
liquid clearance modulation by DA in rats ventilated with HVT, we
studied in four additional groups the effect of 1) the
Na+ channel blocker amiloride (104 M)
instilled into HVT air spaces with 10
4 M DA
(n = 6) and without DA (n = 6), and
2) the Na+-K+-ATP inhibitor ouabain
(5 × 10
4 M) perfused through the pulmonary circulation
in HVT-ventilated rats (n = 6) and HVT rats treated with
10
4 M DA (n = 6).
Group G.
To study the role of the cellular microtubular system on lung liquid
clearance modulation by DA in HVT ventilated rats, we measured active
Na+ transport in rats treated with colchicine (0.25 mg/100
g BW injected intraperitoneally ~15 h before experiments) alone or
with 104 M DA instilled into the air spaces
(n = 6 in each group). We also studied the effects of
DA instilled into the air space in rats treated with
-lumicolchicine
(0.25 mg/100 g BW injected intraperitoneally ~15 h before
experiments; n = 6 in each group).
-Lumicolchicine
is an isomer of colchicine that does not affect the microtubular
system, but it shares many properties of colchicine, such as inhibition
of protein synthesis (33). Accordingly, it has been used
to demonstrate the physiological effects of colchicine on microtubular
disruption. The effects of colchicine (as compared with lumicolchicine)
on the cellular microtubules disruption have been previously reported
in bile secretion studies and lung liquid clearance modulation by
-adrenergic agonists (12, 25).
Isolated Lungs
The isolated perfused rat lung model was used as previously described (2, 3, 17, 22-25). Briefly, rats were anesthetized with 50 mg/kg BW of pentobarbital, tracheotomized, and mechanically ventilated with a tidal volume of 2.5 ml, peak airway pressure of 8-10 cmH2O, and 100% oxygen for 5 min. The chest was opened via a median sternotomy, after which 400 units of heparin sodium were injected into the right ventricle. After exsanguination, the heart and lungs were removed en bloc from the thoracic cavity. We catheterized the pulmonary artery and left atrium and flushed the pulmonary circulation of remaining blood by perfusing with BSA solution containing 135.5 mM Na+, 119.1 mM ClPerfusion of the lungs was performed with 90 ml of the same BSA solution containing 0.16 mg/ml of fluorescein-tagged albumin (FITC-albumin, Sigma). The perfusate was pumped from a lower reservoir to an upper reservoir by a peristaltic pump and from there flowed through the pulmonary artery and exited via the left atrium. Pulmonary artery and left atria pressures were maintained at 12 and 0 cmH2O, respectively, and recorded via a pressure transducer with a zero reference point at the level of the left atrium. Pulmonary artery and left atrium pressures were recorded continuously in a multichannel recorder (Gould 3000 Oscillograph Recorder; Gould, Cleveland, OH). Pulmonary circulation pressures and flow rates were monitored continuously during the experimental protocol.
Samples were drawn from the three reservoirs: air space instillate, pleural bath, and perfusate 10 and 70 min after the experimental protocol was started. To ensure homogeneous sampling from the air spaces, we aspirated and reintroduced 2 ml of instillate into the air spaces three times before removing each sample. This has been shown to provide a reproducibly mixed sample in our laboratory (2, 3, 17, 22-25). All samples were centrifuged at 1,000 g for 15 min. Colorimetric analysis of the supernatant for EBD (absorbance at 620 nm) was performed in a Hitachi model U2000 Spectrophotometer (Hitachi Instruments, San Jose, CA). Analysis of FITC-albumin (excitation 487 nm and emission 520 nm) was performed in a Perkin-Elmer fluorescence spectrometer (model LS-3B; Perkin-Elmer, Oakbrook, IL). 22Na+ and [3H]mannitol were measured in a betacounter (Packard Tricarb, Downers Grove, IL).
Calculations
We calculated the alveolar lining fluid volume (VELF) by instilling into the air spaces 3 ml of fluid (V0) containing a known concentration of albumin (EBD)0, tagged with EBD. After a brief mixing, a sample was removed and the EBD concentration at time t [(EBD)t] was estimated. The amount of EBD is the same in the instillate [V0(EBD)0] and in the lung after initial mixing [(V0 + VELF)(EBD)t]. Equating the two yields
![]() |
(1) |
![]() |
(2) |
![]() |
(3) |
![]() |
(4) |
![]() |
(5) |
Similarly, the mannitol flux (typically expressed as
PA, the permeability-surface area product) is given by
![]() |
(6) |
Albumin flux from the pulmonary circulation into the alveolar space was determined from the fraction of FITC-albumin that appears in the air space during the experimental protocol. These calculations were carried out for each sampling period.
Alveolar Epithelial Type II Cells Isolation and Na+-K+-ATPase Activity
Alveolar epithelial type II (ATII) cells were isolated from adult rat lungs as previously described (3, 5, 23-25). Briefly, the lungs were perfused via the pulmonary artery, lavaged, and digested with 30 U/ml of elastase (Worthington Biochemical, Lakewood, NJ) for 20 min at 37°C. The tissue was minced and filtered through sterile gauze and 70-µm nylon mesh. The crude cell suspension was purified by differential adherence to immunoglobulin G-pretreated dishes, and cell viability was assessed by trypan blue exclusion (>95%). The Na+ pump function was examined in ATII cells cultured for 48 h, pretreated with 10Total RNA Isolation and RT-PCR Analysis
Total cellular RNA from ATII cells incubated with 10The following set of oligonucleotides was used for the amplification of
the Na+-K+-ATPase 1-subunit:
5'-AAT CAT GAA CGA GGA GAG CG-3' and 5'-AGG TGA GGT TGG TGA ACT GC-3',
which correspond to the positions 418-437 and 786-805,
respectively, of the cDNA from the rat gene (consider number 1 the
"A" of the first ATG of the gene). For the amplification of the
Na+-K+-ATPase
1-subunit, the
following set of oligonucleotides was used: 5'-GCA GCT GTA TCA GAA
CAT-3' and 5'-CTC CGA TGC GTT TGG GTT-3', which correspond to positions
37-54 and 1,483-1,500, respectively, of the cDNA from the rat
gene (consider number 1 the "A" of the first ATG of the gene). For
1- and
1-isoforms, amplification was
performed as follows: 25 cycles of 94°C × 1 min, 53°C × 1 min 30 s, and 72°C × 2 min. For the control gene G3PDH,
we performed the amplification using the rat G3PDH Control Amplimer Set
from Clontech (Palo Alto, CA). The RT-PCR data were obtained during the
exponential phase of the PCR reaction. The control gene was amplified
at the same time as the Na+-K+-ATPase
1- or
1-subunit gene.
Cell Lysate and Western Blot Analysis
ATII cells cultured for 48 h were incubated with 10Data Analysis
Data are presented as mean values ± SE; n represents the number of animals in each experimental group. When comparisons were made between two experimental groups, an unpaired Student's t-test was used. When multiple comparisons were made, a one-way analysis of variance was used, followed by a multiple comparison test (Tukey) when the F statistic indicated significance. Results were considered significant when P < 0.05. ![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Lung Permeability in Rats Ventilated with HVT
The lung permeability to small solutes (22Na+ and [3H]mannitol) increased in rats ventilated with HVT compared with LVT ventilated and control nonventilated rats, without significantly changing the movement of FITC-albumin from the pulmonary circulation into rat air space (Table 1). Concordant with previous reports, EBD-bound albumin instilled in the air space was not detected in the perfusate or bath compartments in any of the experimental groups (2, 3, 17, 22-25), confirming that HVT ventilation for 40 min did not significantly increase alveolar epithelial permeability to albumin. Epithelial lining fluid volume was similar in all experimental groups (data not shown).
|
Lung Liquid Clearance During HVT Ventilation
As depicted in Fig. 1, DA instilled into the air space increased lung liquid clearance ~60% above the basal level in control rat lungs. Lung liquid clearance decreased by ~50% in rats exposed to HVT ventilation for 40 min but not in LVT ventilated rats. DA also increased lung liquid clearance in rats ventilated with LVT and HVT to levels similar to those in control nonventilated rats. The Na+ channel blocker amiloride (10
|
|
|
We examined the role of the cellular microtubular system on DA-mediated
lung liquid clearance in HVT ventilated rats. Colchicine (by
depolymerizing microtubuli) inhibited the DA-mediated increase in lung
liquid clearance in rats ventilated with HVT, whereas the isomer
-lumicolchicine did not affect the DA effects on lung clearance
(Fig. 3). Colchicine and
-lumicolchicine did not change lung permeability to small and large
solutes in any experimental group (data not shown).
|
Effect of DA on Na+-K+-ATPase in ATII Cells
As shown in Fig. 4, Na+-K+-ATPase activity increased ~100% over basal levels in ATII cells incubated with 10
|
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The effects of mechanical ventilation in the treatment of patients with acute hypoxemic respiratory failure have been the focus of several studies. Most of these studies have reported that ventilating patients and animals with HVT causes lung function to deteriorate (19, 29). Several investigators have demonstrated in a rat model that HVT ventilation caused lung injury and high permeability pulmonary edema via capillary stress failure, depletion and inactivation of surfactant components, and release of proteolytic enzymes, such as metalloproteinases and cytokines (7, 9-11, 15, 20, 27-32).
In contrast to the modest effect of static lung inflation on alveolar epithelial permeability, cyclic lung inflation during HVT ventilation caused significant lung injury (9, 10, 13, 29, 31). After short periods of HVT ventilation of rats, there were no lasting changes in lung permeability to solutes; however, higher tidal volumes, previous lung injury, or prolonged HVT ventilation caused severe damage to the alveolo-capillary barrier (7, 9-11, 17). Recently it was reported that HVT ventilation of adult rats (tidal volume of ~40 ml/kg and peak airway pressure of 35 cmH2O) increased alveolar epithelial permeability to small solutes and impaired lung edema clearance. These changes of lung liquid clearance were similar to the changes in clearance observed during hyperoxic lung injury (17, 23, 24).
It has been previously reported that DA increased active Na+ transport in normal and hyperoxia-injured rat lungs (2, 3, 24). In the present study we examined whether DA instilled into the air spaces of HVT ventilated rat lungs would improve alveolar fluid reabsorption. In agreement with previous reports, the lung permeability to albumin did not increase significantly in rats ventilated with HVT for up to 40 min (17, 23). Thus the isolated perfused rat lung model allowed us to accurately estimate the active Na+ transport in rats ventilated with HVT (2, 3, 17, 22-25). HVT ventilation for 40 min decreased lung liquid clearance by ~50% and increased alveolar epithelial permeability to small solutes compared with LVT and control nonventilated rats (see Fig. 1 and Table 1). DA increased the lung liquid clearance in rats exposed to HVT ventilation, and the stimulatory effect of DA was proportionally higher in HVT rat lungs compared with LVT and control nonventilated rat lungs (increasing by ~200, ~55, and ~60% above the basal level, respectively). Our data suggest that the alveolar epithelial damage associated with HVT ventilation for 40 min was relatively mild and similar to the hyperoxia lung injury model and did not irreversibly affect the alveolar epithelial function, thus allowing the alveolar epithelium to respond to the dopaminergic stimulation (24). We reason that HVT ventilation probably inhibited Na+-K+-ATPase activity by promoting its endocytosis into intracellular compartments and not permanently damaging the Na+ pump proteins (8). We also reason that DA promoted the exocytosis of the Na+ pumps back into the plasma membrane, thus restoring the lung ability to clear edema.
Additional experiments with the Na+ channel blocker amiloride, placed into the air spaces, and the Na+-K+-ATPase inhibitor ouabain, perfused through the pulmonary circulation, confirmed that the DA effects in HVT ventilated rat lungs were mediated by active Na+ transport modulation. Both amiloride and ouabain inhibited the stimulatory effects of DA on lung liquid clearance in control rats and rats ventilated with HVT, suggesting that DA upregulated the Na+-K+-ATPase and Na+ channel function in rat alveolar epithelium (see Fig. 2). Amiloride and ouabain decreased lung liquid clearance by ~50% in control rats (see Fig. 2A) but not more than HVT alone did in HVT ventilated rats (see Fig. 2B). We propose potential explanations for these discrepancies. One possibility is that HVT ventilation inhibited the same mechanisms that amiloride and ouabain inhibit, namely the Na+ channels and Na+-K+-ATPase. In that case, amiloride and ouabain would not inhibit clearance more than the effects of HVT alone. Another explanation is that our physiological assessment of clearance is not very precise when the changes in liquid clearance are very low, in the ~2-5% range of the total fluid instilled in the lungs.
Alveolar epithelial Na+-K+-ATPase may be
regulated at different levels, including transcription, translation,
translocation from intracellular pools to the plasma membrane, and
conformational changes of Na+ pump at the plasma membrane
(4, 5). It has been proposed that DA effects could be
mediated by the recruitment of Na+ pumps from intracellular
pools to the basolateral membranes of ATII cells (16, 21,
24). Thus we also examined whether the DA effects could be
explained by translocation of ion-transporting proteins from
intracellular pools into the plasma membrane in rats ventilated with
HVT. Disruption of the cellular microtubular system by colchicine
inhibited the stimulatory effects of DA in HVT ventilated rat lungs,
whereas the isomer -lumicolchicine, which shares many effects with
colchicine but does not depolymerize microtubules, did not inhibit the
DA effects (see Fig. 3). We then studied the effect of DA on
Na+-K+-ATPase function in ATII cells.
Short-term exposure of ATII cells to DA (15 min) increased
Na+ pump activity by ~100% above the control group (see
Fig. 4). The disruption of the microtubular system by colchicine
inhibited the stimulatory effects of DA on
Na+-K+-ATPase activity in ATII cells without
changing
1 and
1 mRNA and total protein
levels (see Figs. 4-6).
In summary, our data suggest that DA improves the lung's ability to reabsorb fluid in rats ventilated with HVT. During mechanical ventilation, lung liquid clearance and active Na+ transport modulation by DA were probably mediated by the recruitment and translocation of ion-transporting proteins from intracellular pools to the cell plasma membrane in rat alveolar epithelium and not by the de novo synthesis of Na+ pumps.
![]() |
ACKNOWLEDGEMENTS |
---|
This research was supported in part by National Heart, Lung, and Blood Institute Grant HL-65161; Proyecto Fondo Nacional de Desarrollo Científico y Tecnológico 1990515; and Pontificia Universidad Católica de Chile.
![]() |
FOOTNOTES |
---|
Address for reprint requests and other correspondence: J. I. Sznajder, Pulmonary & Critical Care Medicine, Northwestern Univ., 300 E. Superior, Tarry 14-707, Chicago, IL 60611 (E-mail: j-sznajder{at}nwu.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published February 22, 2002;10.1152/ajplung.00089.2000
Received 7 March 2000; accepted in final form 12 January 2002.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Bachofen, M,
and
Weibel ER.
Structural alterations of lung parenchyma in the adult respiratory distress syndrome.
Clin Chest Med
3:
35-56,
1982[ISI][Medline].
2.
Barnard, ML,
Olivera WG,
Rutschman DM,
Bertorello AM,
Katz AI,
and
Sznajder JI.
Dopamine stimulates sodium transport and liquid clearance in rat lung epithelium.
Am J Respir Crit Care Med
156:
709-714,
1997
3.
Barnard, ML,
Ridge KM,
Saldias F,
Friedman E,
Gare M,
Guerrero C,
Lecuona E,
Bertorello AM,
Katz AI,
and
Sznajder JI.
Stimulation of the dopamine 1 receptor increases lung edema clearance.
Am J Respir Crit Care Med
160:
982-986,
1999
4.
Bertorello, AM,
and
Katz AI.
Regulation of Na+-K+ pump activity: pathways between receptors and effectors.
News Physiol Sci
10:
253-259,
1995
5.
Bertorello, AM,
Ridge KM,
Chibalin AV,
Katz AI,
and
Sznajder JI.
Isoproterenol increases Na+-K+-ATPase activity by membrane insertion of -subunits in lung alveolar cells.
Am J Physiol Lung Cell Mol Physiol
276:
L20-L27,
1999
6.
Chomczynski, P,
and
Sacchi N.
Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction.
Anal Biochem
162:
156-159,
1987[ISI][Medline].
7.
Corbridge, TC,
Wood LDH,
Crawford GP,
Chudoba MJ,
Yanos J,
and
Sznajder JI.
Adverse effects of large tidal volume and low PEEP in canine acid aspiration.
Am Rev Respir Dis
142:
311-315,
1990[ISI][Medline].
8.
Dada, L,
Bertorello A,
Pedemonte C,
Chandel N,
and
Sznajder JI.
Hypoxia inhibits Na,K-ATPase function by endocytosis of its 1 subunit in alveolar epithelial cells (Abstract).
Am J Respir Crit Care Med
163:
A572,
2001.
9.
Dreyfuss, D,
Basset G,
Soler P,
and
Saumon G.
Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats.
Am Rev Respir Dis
132:
880-884,
1985[ISI][Medline].
10.
Dreyfuss, D,
Soler P,
Basset G,
and
Saumon G.
High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure.
Am Rev Respir Dis
137:
1159-1164,
1988[ISI][Medline].
11.
Dreyfuss, D,
Soler P,
and
Saumon G.
Spontaneous resolution of pulmonary edema caused by short periods of cyclic overinflation.
J Appl Physiol
72:
2081-2089,
1992
12.
Dubin, M,
Maurice M,
Feldmann G,
and
Erlinger S.
Influence of colchicine and phalloidin on bile secretion and hepatic ultrastructure in the rat. Possible interaction between microtubules and microfilaments.
Gastroenterology
79:
646-654,
1980[ISI][Medline].
13.
Egan, EA.
Lung inflation, lung solute permeability, and alveolar edema.
J Appl Physiol
53:
121-125,
1982
14.
Haskell, JF,
Yue G,
Benos DJ,
and
Matalon S.
Upregulation of sodium conductive pathways in alveolar type II cells in sublethal hyperoxia.
Am J Physiol Lung Cell Mol Physiol
266:
L30-L37,
1994
15.
John, J,
Taskar V,
Evander E,
Wollmer P,
and
Jonson B.
Additive nature of distention and surfactant perturbation on alveolo-capillary permeability.
Eur Respir J
10:
192-199,
1997
16.
Lecuona, E,
Garcia A,
and
Sznajder JI.
A novel role for protein phosphatase 2A in the dopaminergic regulation of Na,K-ATPase.
FEBS Lett
481:
217-220,
2000[ISI][Medline].
17.
Lecuona, E,
Saldias F,
Comellas A,
Ridge K,
Guerrero C,
and
Sznajder JI.
Ventilator-associated lung injury decreases lung ability to clear edema in rats.
Am J Respir Crit Care Med
159:
603-609,
1999
18.
Matthay, MA,
Folkesson HG,
and
Verkman AS.
Salt and water transport across alveolar and distal airway epithelia in the adult lung.
Am J Physiol Lung Cell Mol Physiol
270:
L487-L503,
1996
19.
Parker, JC,
Hernandez LA,
and
Peevy KJ.
Mechanisms of ventilator-induced lung injury.
Crit Care Med
21:
131-143,
1993[ISI][Medline].
20.
Parker, JC,
Townsley MI,
Rippe B,
Taylor AE,
and
Thigpen J.
Increased microvascular permeability in dog lungs due to high peak airway pressures.
J Appl Physiol
57:
1809-1816,
1984
21.
Ridge KM, Dada L, Lecuona E, Bertorello AM, Katz AI, Mochley-Rosen D,
and Sznajder JI. Dopamine-induced exocytosis of Na,K-ATPase is
dependent on the activation of protein kinase C epsilon and delta.
Mol Biol Cell. In press.
22.
Rutschman, DH,
Olivera W,
and
Sznajder JI.
Active transport and passive liquid movement in isolated perfused rat lungs.
J Appl Physiol
75:
1574-1580,
1993[Abstract].
23.
Saldias, FJ,
Lecuona E,
Comellas AP,
Ridge KM,
Rutschman DH,
and
Sznajder JI.
-Adrenergic stimulation restores rat lung ability to clear edema in ventilator-associated lung injury.
Am J Respir Crit Care Med
162:
282-287,
2000
24.
Saldias, FJ,
Lecuona E,
Comellas AP,
Ridge KM,
and
Sznajder JI.
Dopamine restores lung ability to clear edema in rats exposed to hyperoxia.
Am J Respir Crit Care Med
159:
626-633,
1999
25.
Saldias, F,
Lecuona E,
Friedman E,
Barnard ML,
Ridge KM,
and
Sznajder JI.
Modulation of lung liquid clearance by isoproterenol in rat lungs.
Am J Physiol Lung Cell Mol Physiol
274:
L694-L701,
1998
26.
Saumon, G,
and
Basset G.
Electrolyte and fluid transport across the mature alveolar epithelium.
J Appl Physiol
74:
1-15,
1993[Abstract].
27.
Shirley, HH,
Wolfram CG,
Wasserman K,
and
Mayerson HS.
Capillary permeability to macromolecules: stretched pore phenomenon.
Am J Physiol
190:
189-193,
1957
28.
Staub, NC.
Pulmonary edema.
Physiol Rev
54:
678-811,
1974
29.
Sznajder, JI,
Ridge KM,
Saumon G,
and
Dreyfuss D.
Lung injury induced by mechanical ventilation.
In: Pulmonary Edema, edited by Matthay M,
and Ingbar D.. New York: Marcel Dekker, 1998, p. 413-30.
30.
Tremblay, L,
Valenza F,
Ribeiro SP,
Li J,
and
Slutsky AS.
Injurious ventilatory strategies increase cytokines and c-fos mRNA expression in an isolated rat lung model.
J Clin Invest
99:
944-952,
1997
31.
Webb, HH,
and
Tierney DF.
Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures: protection by positive end-expiratory pressure.
Am Rev Respir Dis
110:
556-565,
1974[ISI][Medline].
32.
West, JB,
Tsukimoto K,
Mathieu-Costello O,
and
Prediletto R.
Stress failure in pulmonary capillaries.
J Appl Physiol
70:
1731-1742,
1991
33.
Wilson, L,
and
Friedkin M.
The biochemical events of mitosis. I. Synthesis and properties of colchicine labeled with tritium in its acetyl moiety.
Biochemistry
5:
2463-2468,
1966[ISI][Medline].