Intratracheal administration of lidocaine (final concentration, 0.66%) proved to be the most reliable method to reduce frequency and intensity of coughing in horses during BAL.
Healthy horses received aerosolised, intranasal or oral doses of 3 mg of fluticasone propionate evenly divided over morning and evening treatments for seven days. The bioavailability of the drug was determined in terms of the suppression of the endogenous cortisol concentrations in the horses during the period of treatment. The horses which received the aerosolised drug had significantly lower concentrations of endogenous cortisol on days 5 and 8 than the horses which received aerosolised placebo. The horses which received nasal and oral doses of fluticasone propionate showed no significant changes in their endogenous cortisol concentrations.
Beta-agonists have been shown to display anti-inflammatory properties in several experimental models. The aim of this study was to investigate the anti-inflammatory properties of clenbuterol (CB), administered either intravenously or by aerosol, in comparison with fluticasone propionate (FP) in recurrent airway obstruction (RAO)-susceptible horses. Eight horses, of which five were known to be susceptible to RAO, underwent an inhalation challenge with Aspergillus fumigatus (AF) antigen and were treated with CB intravenously, CB by aerosol, or FP by aerosol. Twenty-four hours after the challenge, bronchoalveolar lavage was performed, the total and differential cell counts were assessed, and cytokines were measured in isolated alveolar macrophages. After challenge with AF, RAO-susceptible horses showed an increase in total cell count, based on an increase in macrophages and lymphocytes, which was inhibited by treatment with intravenous CB, aerosolized CB and aerosolized FP. Neutrophil ratios were decreased when treated with aerosolized CB and FP. Expression of interleukin (IL)-1beta and IL -8 was significantly increased after AF challenge . Interleukin -1beta was significantly decreased following treatment with intravenous CB, aerosolized CB and aerosolized FP, whereas only FP decreased the expression of IL-8. These data suggest that the anti-inflammatory property of CB provide new opportunities in the therapeutic intervention of early inflammation in RAO.
This study was undertaken to assess the importance of muscarinic receptor subtypes in equine airway disease. Smooth muscle strips from the mid-cervical portion of the trachea of horses were placed in tissue baths and isometric contractile force was measured. Active force was measured in response to metacholine and the selective muscarinic receptor agonists McN-A-343 (M1-selective) and pilocarpine (M2-selective) in cumulative concentrations (10(-9)M through 10(-3)M), with and without preincubation with three or four concentrations of the selective muscarinic receptor antagonists pirenzepine (M1-selective), methoctramine (M2-selective), and 4-DAMP (M3-selective). The tissues contracted in response to all muscarinic agonists. The maximum responses (mean +/- sem) were 86.7 +/- 6.2 g for metacholine, 27.1 +/- 2.5 g for McN-A-343 and 37.6 +/- 3.5 g for pilocarpine. Preincubation with the selective muscarinic receptor antagonists resulted in dose-dependent rightward shifts of the concentration-effect curves for metacholine. pA2 values (means +/- sem) were 8.88 +/- 0.30 for 4-DAMP, 6.53 +/- 0.38 for methoctramine, and 6.72 +/- 0.31 for pirenzepine. Preincubation with 10(-7) M 4-DAMP resulted in a rightward shift of the concentration-effect curves for McN-A-343 and pilocarpine. These results indicate that the most important muscarinic receptor mediating contraction of equine tracheal smooth muscle is of the M3-type. Therefore relatively low concentrations of a M3-selective muscarinic receptor antagonist will inhibit acetylcholine-induced contraction of equine airway smooth muscle.
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