The effects of salbutamol on epithelial ion channels depend on the etiology of acute respiratory distress syndrome but not the route of administration

Introduction

We investigated the effects of intravenous and intratracheal administration of salbutamol on lung morphology and function, expression of ion channels, aquaporin, and markers of inflammation, apoptosis, and alveolar epithelial/endothelial cell damage in experimental pulmonary (p) and extrapulmonary (exp) mild acute respiratory distress syndrome (ARDS).

Methods

In this prospective randomized controlled experimental study, 56 male Wistar rats were randomly assigned to mild ARDS induced by either intratracheal (n = 28, ARDSp) or intraperitoneal (n = 28, ARDSexp) administration of E. coli lipopolysaccharide. Four animals with no lung injury served as controls (NI). After 24 hours, animals were anesthetized, mechanically ventilated in pressure-controlled mode with low tidal volume (6 mL/kg), and randomly assigned to receive salbutamol (SALB) or saline 0.9% (CTRL), intravenously (i.v., 10 μg/kg/h) or intratracheally (bolus, 25 μg). Salbutamol doses were targeted at an increase of ≈ 20% in heart rate. Hemodynamics, lung mechanics, and arterial blood gases were measured before and after (at 30 and 60 min) salbutamol administration. At the end of the experiment, lungs were extracted for analysis of lung histology and molecular biology analysis. Values are expressed as mean ± standard deviation, and fold changes relative to NI, CTRL vs. SALB.

Results

The gene expression of ion channels and aquaporin was increased in mild ARDSp, but not ARDSexp. In ARDSp, intravenous salbutamol resulted in higher gene expression of alveolar epithelial sodium channel (0.20 ± 0.07 vs. 0.68 ± 0.24, p < 0.001), aquaporin-1 (0.44 ± 0.09 vs. 0.96 ± 0.12, p < 0.001) aquaporin-3 (0.31 ± 0.12 vs. 0.93 ± 0.20, p < 0.001), and Na-K-ATPase-α (0.39 ± 0.08 vs. 0.92 ± 0.12, p < 0.001), whereas intratracheal salbutamol increased the gene expression of aquaporin-1 (0.46 ± 0.11 vs. 0.92 ± 0.06, p < 0.001) and Na-K-ATPase-α (0.32 ± 0.07 vs. 0.58 ± 0.15, p < 0.001). In ARDSexp, the gene expression of ion channels and aquaporin was not influenced by salbutamol. Morphological and functional variables and edema formation were not affected by salbutamol in any of the ARDS groups, regardless of the route of administration.

Conclusion

Salbutamol administration increased the expression of alveolar epithelial ion channels and aquaporin in mild ARDSp, but not ARDSexp, with no effects on lung morphology and function or edema formation. These results may contribute to explain the negative effects of β2-agonists on clinical outcome in ARDS.     

Comparison of Airway Responses in Sheep of Different Age in Precision-Cut Lung Slices (PCLS)

Background

Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS) for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages.

Methods

Lambs were delivered spontaneously at term (147d) and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM) and mast cells staining were evaluated.

Results

PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D₄ and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages.

Conclusion

PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies.     

Zum Zug des Kiebitzregenpfeifers,Pluvialis squatarola,in Bulgarian

Abstract

On the migration of the Grey Plover Pluvialis squatarola, in Bulgaria: 137 Bulgarian records (1891 – 1989) were compiled from published and unpublished sources and reviewed. Distribution, phenology, ecology and ethology are described and discussed in comparison with other countries of the Black Sea region.     

Schriftenschau

Ohne Zusammenfassung     

On the present situation of vultures in Bulgaria: A review

Abstract

A review of the literature indicated that about 100 pairs of Egyptian Vultures, less than five pairs each of Griffon Vultures and Black Vultures and no more Lammergeiers breed in Bulgaria.     

Intrazelluläre Zellzotten in Nahrungsvakuolen von Ciliaten

Zusammenfassung 1. Die Nahrungsvakuolen vonMetafolliculina andrewsi entwickeln mit zunehmendem Alter einen Faltensaum, der seine höchste Differenzierung in dem Altersstadium erreicht, wo die stärkste Resorption der Nährstoffe zu vermuten ist.2. Dieser Faltensaum besteht aus lamellenartigen Cytoplasmaprotuberanzen und bewirkt — ähnlich wie der Bürstensaum an der freien Zelloberfläche — innerhalb der Zelle eine erhebliche Oberflächenvergrößerung der Nahrungsvakuole zugunsten der Permeation der Nährstoffe.3. Bei alten Nahrungsvakuolen werden die Falten wieder zurückgebildet, eine Tatsache, die die funktionelle Bedeutung dieser Struktur weiterhin unterstreicht.4. An Hand des Verdauungsgrades des Vakuoleninhalts und der morphologischen Veränderungen der Vakuolenwand lassen sich bei den Nahrungsvakuolen vonMetafolliculina deutlich vier Alters- beziehungsweise Funktionsstadien unterscheiden: 1. Ingestionsvakuolen, 2. Digestionsvakuolen, 3. Resorptionsvakuolen und 4. Egestionsvakuolen.5. Die morphologischen Befunde an der Resorptionsvakuole, die strukturelle und funktionelle Parallelen mit den resorbierenden Darmepithelien von Metazoen aufweist, werden im Rahmen der heutigen Vorstellungen über die zelluläre Stoffaufnahme diskutiert.

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Lamellar microvilli in food vacuoles of ciliates

With progressing age, the food vacuoles ofMetafolliculina adrewsi develop a border of folds, which attains its most pronounced differentiation at a stage where maximum resorption of nutrient substances presumably takes place. This border of folds, similar to the well known brush border at the free cell surface, consists of lamellar cytoplasm protuberances and causes a considerable enlargement of the membrane area of the food vacuole within the cell, thus favoring the permeation of nutrient substances. In old food vacuoles the border of folds undergoes involution, an observation that also points to the functional significance of this structure. InMetafolliculina the degree of digestion of the vacuole contents and the morphological changes of the vacuole wall enable a distinction to be made between 4 different stages of age and function of the food vacuoles respectively: (1) ingestion vacuoles, (2) digestion vacuoles, (3) resorption vacuoles and (4) egestion vacuoles. The resorption vacuole evidently shows structural and functional analogies to the resorbing intestinal epithelia of Metazoa. The morphological findings are discussed in the light of current concepts on substance uptake by the cell.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Tris(trimethylsilyl)stannyl alkali derivatives: Syntheses and NMR spectroscopic properties

Starting from tetrakis(trimethylsilyl)stannane, the tris(trimethylsilyl)stannyl alkali derivatives (Me₃Si)₃SnM, (M = Li, Na, K, Rb, Cs) were prepared in excellent yields. Reaction with MgBr₂ · Et₂O afforded bis[tris(trimethylsilyl)stannyl]magnesium. Reaction products were investigated by means of multinuclear NMR spectroscopy. At low temperatures, coupling of ⁷Li and ¹¹⁹Sn between [(Me₃Si)₃Sn]⁻ and [Li · 3THF]⁺ (337 Hz) or [Li · 12Cr4]⁺ (275 Hz), was observed. NMR chemical shifts and coupling constants of the stannyl anions exhibit a strong dependency on the nature of the cation, solvent system, concentration and temperature. In addition, the molecular structure of tris(trimethylsilyl)stannyl sodium · 15Cr5 was determined by X-ray crystallography. The [Na · 15Cr5]⁺ and [(Me₃Si)₃Sn]⁻ units are joined by a direct Sn-Na contact, 3.0775(18) Å in length.