Pulmonary surfactant release in fetal rabbits as affected by terbutaline and aminophyllin

Ekelund, Laila; Burgoyne, Rosmarie; Brymer, Deborah; Enhörning, Göran

doi:10.3109/00365518109092040

Cited by 28 publications

(17 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When sacrificed 2.5 h later, the lungs of theophylline-treated fetuses retained more air at deflation pressure 10 cm H20, and total phospholipids, recovered from lung lavage fluid were higher, indicating increased release of pulmonary surfactant. However, using similar methods and the same dose of theophylline, we were unable to confirm these results (8) and, in accordance with our observations in the rabbit, Gross et al (personal communication) found that there was no increased release of fetal pulmonary surfactant after infusion of pregnant rats with different dosages of theophylline.…”

contrasting

confidence: 32%

“…Increased release of pulmonary surfactant into the alveolar space might be one effect of xanthines. Several animal studies indicate increased synthesis and/or secretion of fetal surfactant after administration of aminophylline (theophylline ethylenediamine) to the mother or directly to the fetus (3,6,7), but other studies have not confirmed this effect (8). Enprofylline (3-propylxanthine), a new xanthine derivative, exhibits potent antiasthmatic characteristics (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary Surfactant Release in Fetal Rabbits as Affected by Enprofylline

Ekelund

Enhörning

1985

Pediatr Res

Self Cite

View full text Add to dashboard Cite

Respiratory distress syndrome in the newborn is associated with a deficiency of pulmonary surfactant, the main component of which is dipalmitoylphosphatidylcholine (1). A number of pharmacological agents have been found to influence the synthesis of pulmonary surfactant. The effect of glucocorticoids has been studied most extensively, and accelerated lung maturation has been demonstrated in experimental (2, 3) as well as clinical studies (4,5). Xanthines are widely used in lung diseases such as asthma and apnea in premature infants, but the mechanism of action of these drugs is still relatively unknown. Increased release of pulmonary surfactant into the alveolar space might be one effect of xanthines. Several animal studies indicate increased synthesis and/or secretion of fetal surfactant after administration of aminophylline (theophylline ethylenediamine) to the mother or directly to the fetus (3, 6, 7), but other studies have not confirmed this effect (8). Enprofylline (3-propylxanthine), a new xanthine derivative, exhibits potent antiasthmatic characteristics (9). However, the effects of this substance and those of theophylline differ in several respects; most importantly, theophylline is a potent adenosine antagonist, while enprofylline is not (10). Our investigation is an assessment of fetal surfactant release following enprofylline infusion to the doe. MATERIALS AND METHODSEight pregnant New Zealand rabbits were used. Time of mating was known within 1 h. At a gestational age of 27.9 days (term 3 1 days), four does were injected intravenously with enprofylline, 5 mg/kg, during a 5-min period, and, in an identical manner, four controls received the same volume of Ringer's solution. Following this loading dose, the rabbits were continuously infused over the next 2 h with enprofylline, 20 mg/kg, and the controls with the same volume of Ringer's solution. On completion of the infusion, the maternal rabbits were killed with a lethal intravenous dose of thiopental sodium and the abdomen was opened. To prevent the fetuses from making inspiratory efforts, they were injected intracranially with 0.5 ml thiopental sodium while still in utero. The fetuses then were delivered through uterine incisions. The trachea of each fetus was exposed, and a polyethylene tube (PE 50) was inserted just below the larynx. From each fetus, about 25 p1 of lung fluid was collected for evaluation of surface activity with the pulsating bubble surfactometer (1 1). This instrument is particularly appropriate for assessing the effect that surface properties of fetal pulmonary fluid will have on the initial aeration with the first breath and on subsequent breathing. The surfactometer's sample chamber, filled with the airway fluid, communicates with ambient air through a vertical capillary. As fluid is withdrawn from the chamber, air is forced to move down the capillary, the cylindrical "airway," and a bubble, with a radius of 0.55 mm, is developed. While the first breath is thus simulated, the negative pressure in the sample liquid surrounding...

show abstract

contrasting

confidence: 32%

mentioning

confidence: 99%

Pulmonary Surfactant Release in Fetal Rabbits as Affected by Enprofylline

Ekelund

Enhörning

1985

Pediatr Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Stimulation of ß-adrenergic receptors elevates intracellular cAMP, thereby increasing the mRNA levels for surfactant proteins and lipogenic enzymes such as fatty acid synthase [21]. ß-adrenergic agonists have also been shown to induce surfactant secretion and may stimulate surfactant synthesis and recycling in vivo [5,6]. Terbutaline can also activate Na + and K + channels in fetal rat lung epithelium by increasing the cytosolic Ca 2+ concentration [22,23].…”

Section: Discussionmentioning

confidence: 99%

“…In preterm infants, the main effect on the lung observed after antenatal terbutaline exposure is a lower incidence of infant respiratory distress syndrome (IRDS) [3,4]. Antenatal exposure to terbutaline can cause release of surfactant in preterm rabbit pups [5,6], and can decrease the production of luminal liquid over time in fetal lambs [7].…”

Section: Introductionmentioning

confidence: 99%

Antenatal Terbutaline Administration Decreases the Lung Hyaluronan Concentration in Preterm Rabbit Pups

Johnsson¹,

Eriksson

Sedin³

2001

Neonatology

View full text Add to dashboard Cite

Objectiv: To determine whether antenatal exposure to terbutaline alters the lung hyaluronan concentration or lung water content at birth in preterm rabbit pups. Study Design: Rabbit dams (n = 18) with timed pregnancies were injected with 30 µg terbutaline or saline (controls) one day before delivery at 27–29 days of gestation. Pups were killed immediately after delivery. Lung water content and hyaluronan concentrations were determined. Results: Pups exposed antenatally to terbutaline had lower mean lung hyaluronan concentrations than control pups. Lung hyaluronan/dry lung weight was significantly lower in pups delivered at 28 (p = 0.034) or 29 days (p < 0.001), while lung hyaluronan/wet lung weight was significantly lower at all three gestational ages. Conclusion: Antenatal exposure to terbutaline lowers the lung hyaluronan concentration at birth in preterm (27–29 days) rabbit pups without altering the lung water content.

show abstract

“…In addition to bronchodilation, theophylline was recently shown to have immunomodulatory effects [112,113]. Aminophylline was demonstrated to release pulmonary surfactant in foetal rabbits [114]. Another study suggested that aminophylline injected into foetal rabbits leads to increased total phospholipid yield from lung lavage fluids and decreased surface tension as measured by static pressure-volume curves [115].…”

Section: Conventional Antiobstructive Therapymentioning

confidence: 99%

The role of pulmonary surfactant in obstructive airways disease

Hohlfeld

Fabel²,

Hamm³

1997

Eur Respir J

View full text Add to dashboard Cite

Pulmonary surfactant research has an increasing impact on treatment considerations in adult respiratory disorders, above all acute respiratory distress syndrome (ARDS). Obstructive airways diseases have only been sporadically addressed in this respect. In the last decade, direct and circumstantial evidence for surfactant as a contributing factor in the regulation of airway calibre has emerged.Morphologically, a bronchiolar surfactant layer has been demonstrated, whereby the airways are mostly supplied by alveolar surfactant components via the mucociliary escalator. Functionally, prevention of airway film collapse and collapse of the airway walls are important surfactant properties in maintaining airway stability. In addition to its surface activity, airway surfactant improves bronchial clearance and regulates airway liquid balance, thus indirectly modulating airway wall thickness and airway diameter. Surfactant has furthermore been shown to modulate the function of respiratory inflammatory cells. Its immunomodulatory activity includes suppression of cytokine secretion and transcription factor activation. This may be of importance in the inflammatory network of asthma.Thus, dysfunction of surfactant in obstructive lung disease might be one of the mechanisms leading to increased airway resistance, which is commonly thought to be due to narrowing of airways under humoral and nervous control. In animal models of asthma, surfactant dysfunction was demonstrated, which was possibly due to protein inhibition. Furthermore, surfactant therapy seems to be capable of preventing allergen-induced bronchoconstriction. Human studies on surfactant impairment in obstructive airways diseases are still scarce but the data available are consistent with animal studies.Antiobstructive pharmacotherapy, mainly with corticosteroids, might influence and improve airway surfactant balance, but the exact mechanisms and the overall effect of pharmacotherapy on surfactant function in obstructive airways disease has to be further elucidated. Our knowledge about the role of pulmonary surfactant in obstructive airways disease is still limited, but there is convincing evidence that pulmonary surfactant plays a role in keeping the airways open.

show abstract

Pulmonary surfactant release in fetal rabbits as affected by terbutaline and aminophyllin

Cited by 28 publications

References 23 publications

Pulmonary Surfactant Release in Fetal Rabbits as Affected by Enprofylline

Pulmonary Surfactant Release in Fetal Rabbits as Affected by Enprofylline

Antenatal Terbutaline Administration Decreases the Lung Hyaluronan Concentration in Preterm Rabbit Pups

The role of pulmonary surfactant in obstructive airways disease

Contact Info

Product

Resources

About