Techniques for drug delivery to the airways, and the assessment of lung function in animal models

Raeburn, David; Underwood, Stephen L.; Villamil, Maria Elena

doi:10.1016/1056-8719(92)90035-y

Cited by 53 publications

(15 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These practical aspects, while bringing physical comfort for the animal, minimise environmental stresses, which may have detrimental effect on data. Moreover, whole-body chambers can generate relatively uniform and stable aerosol drug concentrations throughout the exposure zone with reduced interexperiment variability [18][19][20]. A disadvantage of wholebody exposure chambers is the considerable loss of inhaled test drugs in the animal fur, eyes and mouth, and in the chamber walls.…”

Section: Discussionmentioning

confidence: 99%

“…Respiratory delivery to mice is technically challenging due to inherent anatomical and physiological animal characteristics, and, particularly, to small animal size [18][19][20]. The nebuliser setup we developed in the present work comprises a wholebody immersion exposure chamber designed for a single mouse.…”

Section: Discussionmentioning

confidence: 99%

“…The nebuliser setup we developed in the present work comprises a wholebody immersion exposure chamber designed for a single mouse. Major advantages of a whole-body inhalation chamber over other methods of inhalation exposure for live animals, including head-only exposures, nose-or mouth-only methods, lung-only exposures, and partial-lung exposures [18][19][20], comprise lack of restraint or anaesthesia during experiment, and a controllable low-stress environment with respect to clean air supply, noise, vibration and lighting exposure. These practical aspects, while bringing physical comfort for the animal, minimise environmental stresses, which may have detrimental effect on data.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Inhaled phosphodiesterase type 5 inhibitors restore chloride transport in cystic fibrosis mice

Lubamba

Lebacq²,

Reychler³

et al. 2010

Eur Respir J

View full text Add to dashboard Cite

Sildenafil and vardenafil, two selective inhibitors of phosphodiesterase type 5 (PDE5) are able, when applied by intraperitoneal injection, to activate chloride transport in cystic fibrosis (CF) mice homozygous for the F508del mutation. Oral treatment with the drugs may be associated with adverse haemodynamic effects. We hypothesised that inhaled PDE5 inhibitors are able to restore ion transport in F508del CF airway epithelium.We developed a restraint-free mouse chamber for inhalation studies. PDE5 inhibitors were nebulised for 15 min at concentrations adjusted from recommended therapeutic oral doses for male erectile dysfunction. We measured in vivo nasal transepithelial potential difference 1 h after a single inhalation of sildenafil, vardenafil or tadalafil in F508del CF and normal homozygous mice.After nebulisation with the drugs in F508del mice, chloride transport, evaluated by perfusing the nasal mucosa with chloride-free buffer containing amiloride followed by forskolin, was normalised; the forskolin response was increased, with the largest values being observed with tadalafil and intermediate values with vardenafil. No detectable effect was observed on sodium conductance.Our results confirm the role of PDE5 inhibitors in restoring chloride transport function of F508del CF transmembrane conductance regulator protein and highlight the potential of inhaled sildenafil, vardenafil and tadalafil as a therapy for CF.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhaled phosphodiesterase type 5 inhibitors restore chloride transport in cystic fibrosis mice

Lubamba

Lebacq²,

Reychler³

et al. 2010

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…The development of animal models of airway hyperreactivity is a common approach to investigate the possible mechanisms involved in the pathogenesis of this phenomenon and additionally, allow the development of novel therapeutic agents which may be of benefit in asthma. Raeburn et al (1992) reviewed a variety of techniques to measure parameters of lung function in small laboratory animals. These include models in which bronchospasm is assessed in anaesthetized, mechanically ventilated animals (Payne & DeNucci, 1987).…”

Section: Introductionmentioning

confidence: 99%

Airway hyper‐ or hyporeactivity to inhaled spasmogens 24 h after ovalbumin challenge of sensitized guinea‐pigs

Lewis

Broadley

1995

British J Pharmacology

View full text Add to dashboard Cite

1 The aim of this study was to determine whether an inhalation of ovalbumin (OA, 10 or 20 mg ml-') by conscious OA-sensitized guinea-pigs leads to airway hyperreactivity to spasmogens 24 h later. In contrast to most previous studies, the spasmogens (5-HT, methacholine (MCh), U-46619 and adenosine) were administered by inhalation and airway function was measured in conscious guinea-pigs. 2 Guinea-pigs were sensitized by i.p. injection of 10 jg OA and 100 mg aluminium hydroxide in 1 ml normal saline; 14-21 days later they were exposed to an inhalation of 5-HT, MCh, U-46619 or adenosine. Specific airway conductance (sGaw) was measured in conscious animals by whole body plethysmography. The spasmogens caused bronchoconstriction, measured as a reduction in sGaw from the pre-inhalation basal values. Dose-related bronchoconstrictions were observed with 5-HT, MCh and U-46619. 3 The effect of an ovalbumin macroshock challenge upon the responses to each spasmogen were examined by giving an inhalation of aerosolized OA at 24 h (or 7 days in the case of adenosine) after an initial spasmogen challenge. Eighteen to twenty-four hours after the OA macroshock, the same guineapigs were exposed to a repeated inhalation of 5-HT, MCh, U-46619 or adenosine. 4 U-46619 was the only spasmogen to demonstrate hyperresponsiveness, the peak change in sGaw being increased from -12.3 + 9.9 to -38.8 + 5.0% by 10 mg ml-' OA challenge. In contrast, the ovalbumin challenge (20 mg ml-') inhibited the bronchoconstrictions to 5-HT (50 jg ml-') and MCh (100 jig ml-'). Adenosine demonstrated bronchoconstriction in sensitized guinea-pigs but no significant change in the response was observed after an OA challenge. 5 All results were compared with a control group of sensitized guinea-pigs receiving a NaCl challenge. The bronchoconstrictor responses to 5-HT, MCh, U-46619 or adenosine did not differ significantly before and after the saline challenge, indicating reproducibility of the responses. 6 In further experiments, guinea-pigs were exposed to inhalation of 5-HT (50 jg ml-') or MCh (300 jg ml-') 24 h before atropine (10 jig, 100 jg or 1 mg ml-') and again at 0.5 to 1.5 h afterwards. Atropine antagonized the 5-HT-and MCh-induced bronchoconstrictions over the same antagonist doserange. This suggests that the bronchoconstriction induced in the conscious guinea-pig by 5-HT is mediated primarily via muscarinic receptors, possibly by a vagal reflex. The inhibition of the responses to 5-HT and MCh by OA challenge would therefore appear to be related to interference with a common cholinergic pathway for these spasmogens. 7 In summary, airway hyperresponsiveness was evident at 24 h after OA challenge as measured by an enhanced bronchoconstrictor response to inhaled U-46619. When 5-HT or MCh were used as the spasmogens, an opposing decrease in responsiveness was observed. This was presumed to be due to an inhibition of cholinergic pathways by the OA challenge. Adenosine caused a bronchoconstriction in the sensitized animals but this was not enhanced by the OA ...

show abstract

“…At this time-point the mice were anaesthetized by intraperitoneal injection of 0.25 ml sodium pentobarbitone (60 mg ml-'). Abdomen (Raeburn et al, 1992). In previous experiments it was established that this time-point was optimal for measuring airway hyperresponsiveness in vivo (Hessel et al, 1996).…”

Section: Airway Responsiveness In Vitromentioning

confidence: 99%

Effect of dexamethasone and endogenous corticosterone on airway hyperresponsiveness and eosinophilia in the mouse

Bie

Hessel

Ark

et al. 1996

British J Pharmacology

View full text Add to dashboard Cite

1 Mice were sensitized by 7 intraperitoneal injections of ovalbumin without adjuvant (10 /tg in 0.5 ml of sterile saline) on alternate days and after 3 weeks exposed to either ovalbumin (2 mg ml1-in sterile saline) or saline aerosol for 5 min on 8 consecutive days. One day before the first challenge, animals were injected intraperitoneally on a daily basis with vehicle (0.25 ml sterile saline), dexamethasone (0.5 mg kg'-) or metyrapone (30 mg kg'-). 2 In vehicle-treated ovalbumin-sensitized animals ovalbumin challenge induced a significant increase of airway responsiveness to metacholine both in vitro (27%, P<0.05) and in vivo (40%, P<0.05) compared to saline-challenged mice. Virtually no eosinophils could be detected after saline challenge, whereas the numbers of eosinophils were significantly increased (P<0.01) at both 3 and 24 h after the last ovalbumin challenge (5.48 + 3.8 x I03 and 9.13 + 1.7 x 103 cells, respectively). Furthermore, a significant increase in ovalbumin-specific immunoglobulin E level (583+103 units ml-', P<0.05) was observed after ovalbumin challenge compared to saline challenge (201 + 38 units ml-1). 4 From these data it can be concluded that exogenously applied corticosteroids can inhibit eosinophil infiltration as well as airway hyperresponsiveness. Vise versa, endogenously produced corticosteroids play a down-regulating role on the induction of both eosinophil infiltration and airway hyperresponsiveness.

show abstract

Techniques for drug delivery to the airways, and the assessment of lung function in animal models

Cited by 53 publications

References 79 publications

Inhaled phosphodiesterase type 5 inhibitors restore chloride transport in cystic fibrosis mice

Inhaled phosphodiesterase type 5 inhibitors restore chloride transport in cystic fibrosis mice

Airway hyper‐ or hyporeactivity to inhaled spasmogens 24 h after ovalbumin challenge of sensitized guinea‐pigs

Effect of dexamethasone and endogenous corticosterone on airway hyperresponsiveness and eosinophilia in the mouse

Contact Info

Product

Resources

About