Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep.

Berthiaume, Yves; Staub, Norman C.; Matthay, Michael A.

doi:10.1172/jci112817

Cited by 312 publications

(266 citation statements)

References 26 publications

(43 reference statements)

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“…All of this prepared the lungs for labor induction, having an additive stimulatory effect on lung fluid absorption after IL-1␤ stimulation and preterm delivery. It has also been demonstrated (3,5,6,19,31) that lung fluid is reabsorbed secondary to Na ϩ absorption and that this Na ϩ transport can be stimulated by agonist binding to ␤-adrenoceptors. Consequently, more ␤-adrenoceptors and higher ␤-adrenoceptor stimulation may lead to increased Na ϩ and fluid transport.…”

Section: Discussionmentioning

confidence: 98%

“…Catecholamine stimulation has previously been linked to stimulation of fetal and adult lung fluid absorption (5,6,17,35,38,45). In fact, maternal IL-1␤ pretreatment increased ␤-adrenoceptor expression in fetal lungs, as well as increasing propranolol sensitivity (48).…”

Section: Discussionmentioning

confidence: 99%

“…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-1␤ pretreatment of timed-pregnant guinea pigs induced fluid absorption in fetal lungs, sodium transporter protein, and ␤-adrenoceptor expression via hypothalamus-pituitary-adrenal gland axis stimulation (48).Lung fluid absorption occurs secondarily to transepithelial Na ϩ absorption (3,5,8,17,22,31,35,37,45,48,49) and is driven by basolateral Na-K-ATPases (16, 23) and apical epithelial sodium channels (19,22,30,31). Fluid absorption occurs in near-term lungs (6,17,35,37,45) and is induced/ stimulated by cortisol and triiodothyronine (2, 20, 48) and labor-released epinephrine (17,35,45).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…A segment of the right lower lobe was excised and homogenized for gravimetric measurement of the extravascular water-todry weight ratio by standard methods (5,20) in lungs from 21 of the 23 donors in whom unstimulated rates of alveolar fluid clearance were measured. The extravascular water-to-dry weight ratio of normal lung is 3.2-4.2 (37).…”

Section: Measurement Of Extravascular Water-to-dry Weight Ratiomentioning

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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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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“…2 In mice, deletion of the a subunit of the amiloride-sensitive epithelial sodium channel leads to neonatal death because of failure to clear the liquid from the lungs 3 ; experimentally induced dysfunction of this channel impairs the clearance of alveolar fluid and predisposes mice to pulmonary edema. 4 Betaadrenergic agonists increase vectorial sodium transport in vitro, 5 enhance the clearance of alveolar fluid in the resected human lung 6 and in several species of animals, [7][8][9][10] and accelerate the resolution of pulmonary edema in animal models of lung injury. [11][12][13][14][15] However, the effects of beta-adrenergic agonists in the treatment of pulmonary edema in humans have not been assessed, and information demonstrating the importance of this vectorial sodium transport in the development of and recovery from pulmonary edema in humans is sparse and indirect.…”

Section: Resultsmentioning

confidence: 99%

Salmeterol for the Prevention of High-Altitude Pulmonary Edema

2002

N Engl J Med

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Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep.

Cited by 312 publications

References 26 publications

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

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

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

Salmeterol for the Prevention of High-Altitude Pulmonary Edema

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