Stimulation of lung epithelial liquid clearance by endogenous release of catecholamines in septic shock in anesthetized rats.

Pittet, Jean–François; Wiener-Kronish, J. P.; McElroy, Mary C.; Folkesson, Hans G.; Matthay, Michael A.

doi:10.1172/jci117383

Cited by 196 publications

(190 citation statements)

References 49 publications

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“…Net alveolar fluid clearance was measured by using our usual method but with minor modifications (28,31,32). After the excised lungs were placed in plastic bags with the mainstem bronchi accessible, a segmental bronchus was occluded by a 3-mm balloon tracheal tubing and inflated to 10 cmH 2O with 100% O2.…”

Section: Methodsmentioning

confidence: 99%

“…In a subgroup of lungs, a second sample of alveolar fluid was aspirated after 2 h. 125 I-albumin activity was measured in the supernatants of the aspirates after centrifugation at 3,000 rpm ϫ 10 min. The unstimulated rate of alveolar fluid clearance was measured by comparing the 125 I-albumin activity of the aspirate at the end of the 1-or 2-h time period with the 125 I-albumin activity of a baseline aspirate obtained 2 min after instillation (13,28,31,32). In a subset of lungs (8 pairs), stimulated alveolar fluid clearance was measured by adding 10 Ϫ4 M terbutaline to the instillate.…”

Section: Methodsmentioning

confidence: 99%

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Selected Contribution: Mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung

Ware

Fang

Wang

et al. 2002

Journal of Applied Physiology

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nary edema is common in organ donors and lung transplant recipients. Therefore, we assessed the responsiveness of human donor lungs to pharmacological agents that stimulate clearance of alveolar edema. Organ donors whose lungs were rejected for transplantation were studied. After resection, transport (4°C), and rewarming (37°C) of lungs, alveolar fluid clearance was measured with (n ϭ 8 donors) or without (n ϭ 23 donors) ␤-adrenergic stimulation. Terbutaline-stimulated clearance (10 Ϫ4 M) was higher than unstimulated clearance (7.1 Ϯ 1.3 vs. 4.8 Ϯ 2.4%/h, P Ͻ 0.01). Second, we determined whether medications given to the organ donor were associated with the extent of pulmonary edema or the rate of alveolar fluid clearance in the harvested lung. Preharvest administration of dopamine in low to moderate doses was associated with faster alveolar fluid clearance (r ϭ 0.62, P Ͻ 0.01). Preharvest administration of diuretics was associated with lower extravascular lung water-to-dry weight ratios. This study provides the first evidence that a ␤ 2-adrenergic agonist stimulates alveolar fluid clearance in the human donor lung. Aerosolized ␤ 2-adrenergic agonists may have therapeutic value for hastening the resolution of alveolar edema during the management of donors before resection of lungs for transplantation or in the posttransplant setting. pulmonary edema; ␤-agonist; alveolar epithelial fluid transport; alveolar epithelium; lung preservation PULMONARY EDEMA IS A COMMON problem in both organ donors and lung transplant recipients. In organ do-

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Selected Contribution: Mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung

Ware

Fang

Wang

et al. 2002

Journal of Applied Physiology

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“…The other four guinea pigs remained anesthetized until the 1-h experimental time had passed and were then killed, and samples were obtained. At this time, a blood sample was obtained for FD70 analysis, and the lungs were collected for determination of extravascular plasma equivalents as previously described (31,34,40,46). Trichloroacetic acid (TCA) precipitation of plasma and urine samples verified that the FITC label (Ͼ97%) remained bound to the dextran tracer throughout the experimental time period.…”

Section: Endothelial and Epithelial Protein Permeabilitymentioning

confidence: 99%

“…Passage of FD70 molecules across the endothelial-epithelial barriers was considered to be equal to that of albumin, since they have similar molecular masses (70 vs. 68 kDa). The theory and method behind the plasma equivalent determination have been described in multiple published reports and in various animal species (31,34,40,46). We calculated endothelial protein leak using the FD70 concentrations in the different compartments and applying them in the equation:…”

Section: Endothelial and Epithelial Protein Permeabilitymentioning

confidence: 99%

Oxytocin-induced labor augments IL-1β-stimulated lung fluid absorption in fetal guinea pig lungs

Nair¹,

Li²,

Bhattacharjee³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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-We tested the hypothesis that oxytocin-induced labor augmented IL-1␤-induced/ -stimulated lung fluid absorption in preterm guinea pig fetuses. IL-1␤ was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. At day 3, oxytocin was administered, and fetuses were delivered by abdominal hysterotomy at 61 and by oxytocin-induced birth at 68 days gestation. Delivered fetuses were instilled with isosmolar 5% albumin into the lungs, and lung fluid movement was measured over 1 h by mass balance. Lung fluid absorption was induced in 61-day and stimulated in 68-day gestation lungs by IL-1␤. Labor induction by oxytocin augmented IL-1␤-induced/-stimulated lung fluid absorption. Metyrapone pretreatment did not affect oxytocin-induced/-stimulated lung fluid absorption, while completely blocking IL-1␤-induced/-stimulated fluid absorption. Fetal lung fluid absorption, when present, was always propranolol and amiloride sensitive, suggesting that ␤-adrenoceptor stimulation and amiloridesensitive sodium channels were critical for fluid absorption. Epithelial sodium channel and Na-K-ATPase subunit expressions were both increased by IL-1␤, but not further by oxytocin. Our results indicate that IL-1␤ release into the maternal blood circulation positively affects lung maturation due to the IL-1␤-induced release of cortisol and thus prepares the lungs for the epinephrine surge associated with labor.␤-adrenoceptors; cortisol; epinephrine; prenatal lung development; sodium transport CYTOKINES, SUCH AS INTERLEUKIN-1 (IL-1), can be important during pregnancy, because IL-1 has been detected in the placenta and amniotic fluid (12,44). In this regard, interleukins have been proposed as a signal for parturition onset, as cytokines can stimulate prostaglandin biosynthesis (41). During normal pregnancies, IL-1 is present in the amniotic fluid in low concentrations, but during preterm labor much higher amniotic fluid IL-1 concentrations are present (44). Intrauterine infection/inflammation may further elevate cytokine levels, the highest activity being attributable to IL-1␤ (44). Many prematurely born infants suffer from fetal infection and/or respiratory distress syndrome (RDS), both of which are important reasons for mortality of premature babies. Recent human data suggest that ion transport abnormalities across lung epithelial cells, i.e., an incomplete transition of lung fluid secretion to lung fluid absorption, can contribute to RDS development (1). Factors accelerating ion transport across alveolar cells may thus have benefits for the resolution of RDS. Recent experimental data have suggested that proinflammatory cytokines could also promote lung maturation (9,14,26,47). IL-1␣ increased mRNA surfactant protein expression and improved lung compliance in fetal rabbits (9). IL-1␣ also improved postnatal lung function with increased surfactant pool size without eliciting systemic inflammatory responses in lambs (14, 47). We recently reported that IL-...

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“…In humans, impaired ENaC activity may contribute to neonatal respiratory distress syndrome (8). ENaC-dependent salt and liquid absorption may also help clear pulmonary edema fluid in adult patients (9).…”

mentioning

confidence: 99%

Drosophila DEG/ENaC pickpocket genes are expressed in the tracheal system, where they may be involved in liquid clearance

Liu

Johnson

Welsh

2003

Proc. Natl. Acad. Sci. U.S.A.

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The Drosophila tracheal system and mammalian airways are branching networks of tubular epithelia that deliver oxygen to the organism. In mammals, the epithelial Na ؉ channel (ENaC) helps clear liquid from airways at the time of birth and removes liquid from the airspaces in adults. We tested the hypothesis that related Drosophila degenerin (DEG)͞ENaC family members might play a similar role in the fly. Among 16 Drosophila DEG͞ENaC genes, called pickpocket (PPK) genes, we found 9 expressed in the tracheal system. By in situ hybridization, expression appeared in late-stage embryos after tracheal tube formation, with individual PPK genes showing distinct temporal and spatial expression patterns as development progressed. Promoters for several PPK genes drove reporter gene expression in the larval and adult tracheal systems. Adding the DEG͞ENaC channel blocker amiloride to the medium inhibited liquid clearance from the trachea of first instar larvae. Moreover, when RNA interference was used to silence PPK4 and PPK11, larvae failed to clear tracheal liquid. These data suggest substantial molecular diversity of DEG͞ENaC channel expression in the Drosophila tracheal system where the PPK proteins likely play a role in Na ؉ absorption. Extensive similarities between Drosophila and mammalian airways offer opportunities for genetic studies that may decipher further the structure and function of DEG͞ENaC proteins and development of the airways.trachea ͉ Na ϩ channel ͉ absorption ͉ epithelia ͉ amiloride C omplex multicellular organisms require an elaborate oxygen delivery system to meet tissue metabolic demands. In mammalian lung, a network of branching epithelial tubes carries oxygen to the alveoli, where it diffuses into blood to be distributed to the tissues. Drosophila melanogaster also possesses a network of branching epithelial tubes through which oxygen diffuses to reach cells throughout the organism (1). In addition to their functional similarity, the growth factors and transcription factors controlling branching morphogenesis in mammalian airways and the fly tracheal system share numerous features (2). Moreover, at specific points in development, both systems must convert from liquid-to air-filled tubules. In mammals, this conversion occurs at birth, when the epithelium actively absorbs salt and hence liquid from the airways. In Drosophila, this conversion occurs 2 h before larvae emerge, also by active epithelial absorption (1).In mammalian airways, the epithelial Na ϩ channel (ENaC), composed of ␣-, ␤-, and ␥-ENaC subunits, contributes to salt and liquid absorption (3, 4). Striking evidence for this role came from mice bearing targeted disruptions of ENaC genes. Mice with a disrupted ␣-ENaC gene died shortly after birth, because they failed to clear lung liquid, and mice with disrupted ␤-or ␥-ENaC genes showed delayed lung liquid clearance (5-7). In humans, impaired ENaC activity may contribute to neonatal respiratory distress syndrome (8). ENaC-dependent salt and liquid absorption may also help clear pulmonary ed...

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Stimulation of lung epithelial liquid clearance by endogenous release of catecholamines in septic shock in anesthetized rats.

Cited by 196 publications

References 49 publications

Selected Contribution: Mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung

Selected Contribution: Mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung

Oxytocin-induced labor augments IL-1β-stimulated lung fluid absorption in fetal guinea pig lungs

Drosophila DEG/ENaC pickpocket genes are expressed in the tracheal system, where they may be involved in liquid clearance

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