Topic:Bronchodilation
Bronchodilation refers to the physiological process of widening the air passages in the lungs, facilitated by the relaxation of bronchial smooth muscle. In horses, bronchodilation is significant due to its impact on respiratory efficiency and its relevance in managing equine respiratory conditions such as heaves (recurrent airway obstruction) and inflammatory airway disease. Various pharmacological agents, including beta-agonists and anticholinergics, are employed to induce bronchodilation in horses, aiding in the alleviation of airway obstruction and improvement of airflow. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, therapeutic applications, and effects of bronchodilation in equine respiratory health.
Effect of inhaled beta 2 adrenoceptor agonist, albuterol sulphate, on performance of horses. This study was designed to test the hypothesis that a specific beta 2 adrenergic receptor agonist, albuterol sulphate, when delivered by metered-dose inhaler (MDI) would affect the performance of Thoroughbred horses during incremental exercise testing. Six conditioned Thoroughbred horses were randomly assigned to one of 2 treatment groups: Group 1 horses received placebo and Group 2 received albuterol. Each horse received both treatments in a crossover design with a 3 week interval between trials. Horses inspired albuterol (900 micrograms) or placebo over a 5 min period followed by an incremen...
Equine respiratory pharmacology. Differentiation of diseases of the equine respiratory tract is based on history, clinical signs, auscultation, endoscopy, imaging, and sampling of airway exudate. Upper respiratory therapies include surgical correction of airway obstructions; flushing of localized abscesses (strangles), guttural pouch disease, or sinusitis; and oral or parenteral antibiotic and anti-inflammatory therapy if deemed necessary. Pneumonia usually is treated with antimicrobials, anti-inflammatories, and bronchodilators. Pleural drainage is indicated if significant pleural effusion is present. The most commonly used ...
Monthly, daily, and circadian variations of measurements of pulmonary mechanics in horses with chronic obstructive pulmonary disease. To determine temporal variations of pulmonary function in horses without respiratory tract disease (controls) and horses with chronic obstructive pulmonary disease (COPD) and determine whether reversibility of airway obstruction after environmental control can be predicted by response to atropine administration. Methods: 7 COPD-affected and 5 control horses. Methods: Pulmonary function testing was performed monthly during 3 consecutive months, daily for 5 consecutive days, and at 6-hour intervals for 24 hours before and after administration of atropine (0.02 mg/kg of body weight, i.v.) and aft...
Airway responses to histamine aerosol in clinically normal foods. To describe the spectrum of nonspecific airway reactivity in a group of clinically normal foals. Methods: 12 clinically normal mixed-breed foals, 48 to 92 days old, without history of clinical lung disease. Methods: Nonspecific airway reactivity was determined by measuring the extent of changes in dynamic compliance during nebulization of incrementally increasing concentrations of histamine aerosol. Degree of airway reactivity was expressed as the dose of histamine that evoked a decrease in dynamic compliance (Cdyn) to 65% of the after saline nebulization value (PC65Cdyn) or increase in pulmon...
Pulmonary distribution of aerosolized technetium Tc 99m pentetate after administration of a single dose of aerosolized albuterol sulfate in horses with recurrent airway obstruction. To determine whether pulmonary distribution of aerosolized technetium Tc 99m pentetate is improved after inhalation of a single dose of albuterol sulfate in horses susceptible to recurrent airway obstruction (heaves). Methods: 6 horses with heaves and 4 horses with normal respiratory tract function. Methods: Images were obtained during ventilation of horses at baseline (maximal change in pleural pressure during tidal breathing [deltaPpImax] >15 cm H2O) and after aerosolized albuterol sulfate (360 microg) administration, with a 24-hour washout period between experiments. The deltaPpImax was ...
Aerosolized albuterol sulfate used as a bronchodilator in horses with recurrent airway obstruction. To determine the dose of aerosolized albuterol sulfate required to cause bronchodilation in horses with recurrent airway obstruction (RAO) and duration of this effect. Methods: 19 horses with RAO (10 in experiment 1; 9 in experiment 2). Methods: Horses were moved from pasture to stables, and airway obstruction was induced. Pulmonary function was measured in 10 horses before and 5, 10, and 30 minutes after administration of vehicle or 120, 240, 360, or 720 microg of the drug. Nine horses received vehicle or 360 or 720 microg of albuterol, and pulmonary function was measured at baseline and 5 mi...
Determinants of the maximal change in pleural pressure during tidal breathing in COPD-affected horses. In six COPD-affected horses, we analysed the factors responsible for the changes in pleural pressure (delta Pplmax) that occur during tidal breathing. Four-hundred-and-sixty-eight measurements of each parameter: pulmonary resistance (RL), dynamic elastance (Edyn), air flow rates, and the timing of breathing, were gathered during a trial of the bronchodilator pirbuterol. Data were placed into seven ranks, based on the magnitude of delta Pplmax; rank 1: 5-15; rank 2: 15-25; rank 3: 25-35; rank 4: 35-45; rank 5: 45-55; rank 6: 55-65; and rank 7 > 65 cm H2O. Up to rank 4 (45 cm H2O), the increa...
Comparison of forced oscillation with the conventional method for histamine bronchoprovocation testing in horses. To compare response of horses to histamine bronchoprovocation (HBP), using total respiratory resistance (Rrs) measured by forced oscillatory mechanics (FOM) with dynamic compliance (Cdyn) and pulmonary resistance (RL) measured by the esophageal balloon method. Methods: 10 horses with various degrees of airway reactivity. Methods: The 2 methods for measuring airway responses to HBP were performed on separate days. Endpoints compared were increase of 150 or 200% of baseline Rrs (PC150Rrs, PC200Rrs) and to 150% of baseline RL (PC150RL) or decrease to 65% of baseline Cdyn (PC65Cdyn). Frequency dep...
Effects of inhaled dry powder ipratropium bromide on recovery from exercise of horses with COPD. The present study evaluated ventilatory, cardiovascular and metabolic parameters during recovery from strenuous exercise in horses suffering from a crisis of chronic obstructive pulmonary disease (COPD) and to determine whether ipratropium dry powder inhalation (DPI) before exercise has an effect on these parameters. When 6 saddle horses, affected with COPD, developed airway obstruction, they inhaled placebo and ipratropium (2400 microg/horse), the order being randomly chosen. Pulmonary function tests were then recorded 15 min after inhalation. Following these tests, the horses underwent a str...
A comparison between clenbuterol, salbutamol and terbutaline in relation to receptor binding and in vitro relaxation of equine tracheal muscle. Beta2-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine. We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chambers. The affinities of these drugs to the be...
Pulmonary function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. To determine changes in clinical signs of disease and response to pulmonary function testing in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. Methods: 6 horses with inducible and reversible heaves. Methods: Episodes of heaves were induced by exposure (challenge) to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone dipropionate, parenterally administered dexamethasone, aerosolized propellant [control]), and respiratory frequency and s...
Effect of the 5-lipoxygenase inhibitor, fenleuton, on antigen-induced neutrophil accumulation and lung function changes in horses with chronic obstructive pulmonary disease. The leukotrienes (LT) LTD4 and LTB4 have been shown to cause bronchoconstriction and neutrophil accumulation, respectively, in horse lungs. Such changes are characteristic of the equine allergic respiratory disease, chronic obstructive pulmonary disease (COPD). To further investigate the role of these putative mediators in the pathogenesis of equine COPD the effect of a 5-lipoxygenase inhibitor, fenleuton, on antigen-induced changes in horses with this condition has been examined. Six horses with COPD underwent a series of four antigen challenges, one month apart, with placebo pre-treatment on...
Detection and determination of theobromine and caffeine in urine after administration of chocolate-coated peanuts to horses. The objective of this study was to determine the urinary excretion of methylxanthines in horses following ingestion of chocolate over eight days. The study was performed in response to gas chromatography-mass spectrometry (GC-MS) confirmation of the presence of caffeine in a positive urine test in a racehorse. The trainer of the horse alleged that he often administered chocolate-coated peanuts as treats to his horses, and he believed that the ingestion of chocolate was responsible for the positive urine test. The urinary excretion of theobromine and caffeine after the ingestion of chocolate-co...
Effects of inhaled beclomethasone dipropionate on respiratory function in horses with chronic obstructive pulmonary disease (COPD). The effects of beclomethasone dipropionate on pulmonary function and arterial blood gas values were investigated in horses with chronic obstructive pulmonary disease (COPD). Six mature mares, diagnosed as having COPD based on clinical signs, cytological examination of bronchoalveolar lavage and pulmonary function testing, were used. Beclomethasone dipropionate (3750 microg) was administered b.i.d. for a 2 week period with a metered dose inhaler using a mask. Pulmonary function tests and arterial blood gas analyses were performed at weekly intervals, starting before beclomethasone administratio...
Illegal use of beta-adrenergic agonists: European Community. The use of veterinary medicinal products within the European Community is governed by a series of directives and regulations that describe the requirements for safety, quality, and efficacy of these products. Veterinary therapeutic use of beta-agonists has only been approved in the case of clenbuterol for bronchodilatation in horses and calves and for tocolysis in cows. No beta-agonists have been permitted in the European Community for growth-promoting purposes in farm animals. Surveillance for the presence of residues of veterinary agents in food-producing animals and meat is regulated by the...
Effects of enantiomers of beta 2-agonists on ACh release and smooth muscle contraction in the trachea. The beta 2-agonists currently used as bronchodilators are racemic mixtures of R- and S-enantiomers. In the present study, we examined the effects of enantiomers of the beta 2-agonists albuterol and formoterol on acetylcholine (ACh) release from equine trachealis parasympathetic nerves. ACh release was evoked by electrical field stimulation (20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography coupled with electrochemical detection. We also tested the effects of enantiomers of albuterol and formoterol on equine tracheal smooth muscle (TSM) contraction in response to exog...
Technical validation of a face mask adapted for dry powder inhalation in the equine species. Development of dry powder inhalation (DPI) for horses requires the use of an adapted face mask. In experiment I, 4 masks (A, B, C and D) were tested and factors influencing the delivery of the dry powder were determined. Mask A was one which is commercially available for metered-dose inhalation. Mask B had the same shape as Mask A but an airtight rubber seal was added for the connection between the mask and horse's head. Mask C was a prototype adapted for DPI with connection for the DPI device between the nostrils, airtight expiratory valves in front of each nostril and airtight rubber seal to...
Inhaled medications and bronchodilator usage in the horse. The advantages of aerosol medications include the direct, topical application to the target organ (airways); rapid effect; and low systemic availability. There are now more efficient methods for aerosol delivery that facilitate the use of increasingly sophisticated aerosol drugs. This article reviews the principles of aerosol deposition and the pharmacology of current medications.
Airway response of horses with COPD to dry powder inhalation of ipratropium bromide. To determine the effects of the dry powder inhalation (DPI) of ipratropium bromide (ipratropium) on the airways of health horses and the dose-response curve in horses suffering from chronic obstructive pulmonary disease (COPD) by means of pulmonary function tests, five healthy horses were first studied. Ipratropium (2400 micrograms ipratropium horse-1) was contained in gelatine capsules and administered using a dry powder device connected to an adapted face mask. Pulmonary function tests were recorded before inhalation and 15 and 60 min after inhalation. No modification of pulmonary function w...
Comparative pharmacokinetics of caffeine and three metabolites in clinically normal horses and donkeys. To determine whether clearance of capacity-limited drugs in horses differs from that in donkeys by comparing the serum disposition of caffeine and its metabolites, theophylline, theobromine, and paraxanthine after i.v. administration of caffeine to horses and donkeys. Methods: 4 healthy horses and 5 healthy donkeys. Methods: Blood samples were collected from each animal at time 0 (before) and 5, 10, 15, 20, 30, and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24, 30, 36, 48, 54, 60, 72, and 96 hours after IV administration of a bolus of caffeine. Serum was analyzed in triplicate by high-performance l...
Relaxation of equine tracheal muscle in vitro by different adrenoceptor drugs. Strips of tracheal smooth muscle from 12 horses were contracted by carbachol in tissue baths under isometric conditions. This contraction (approximately 50% of maximum: EC50) was relaxed completely with adrenoceptor drugs. The only exception was clenbuterol, where the degree of relaxation was approximately 90%. In all horses the EC50-value for isoprenaline (mean 1.6 x 10(-8) M) was less than that for adrenaline (mean 9.6 x 10(-8) M) and noradrenaline (mean 1.8 x 10(-6) M). The potency ratio was 1 < 6 < 110 which indicates that the beta 2-subtype dominates among the beta-adrenoceptors of ...
Use of a hand-held, metered-dose aerosol delivery device to administer pirbuterol acetate to horses with ‘heaves’. Aerosol administration of bronchodilators to horses is recommended for treatment of certain airway diseases such as 'heaves'. We have developed a novel, hand-held, metered-dose inhaler and we sought to determine the bronchodilator efficacy of the beta 2 adrenoceptor agonist pirbuterol delivered by this device to horses affected with 'heaves'. To induce airway obstruction, 6 heaves-susceptible horses were stabled, bedded on straw and fed hay. When the maximum change in pleural pressure during tidal breathing (delta Pplmax) was greater than 20 cmH2O on 2 consecutive days, pulmonary function was ...
Potentiation of acetylcholine release from tracheal parasympathetic nerves by cAMP. We tested the hypothesis that increasing intracellular levels of adenosine 3', 5'-cyclic monophosphate (cAMP) increases acetylcholine (ACh) release from airway parasympathetic nerves. Muscle strips from equine trachea were preincubated for 60 min with 10(-7)M atropine, 10(-6)M neostigmine, and 10(-5) M guanethidine. The ACh release was evoked by electrical field stimulation (EFS, 20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography with electrochemical detection. Agents known to increase cAMP, i.e., forskolin (10(-6) - 10(-4) M), 8-bromoadenosine 3', 5'-cyclic monophosp...
Clinical efficacy and safety of clenbuterol HCl when administered to effect in horses with chronic obstructive pulmonary disease (COPD). A field study of 239 horses was conducted to determine the efficacy and safety of clenbuterol HCl, a beta 2-adrenergic bronchodilator, when administered incrementally to effect in the treatment of chronic obstructive pulmonary disease (COPD). The severity of COPD (heaves) and response to treatment was determined by clinical evaluation; an overall 'heaveiness rating' (OHR) was assigned at each observation. The horses were treated orally b.i.d. with clenbuterol (as Ventipulmin Syrup), beginning with the lowest dosage of 0.8 micrograms/kg. On day 10 of treatment at the effective dose (0.8, 1.6, 2...
The rapid and effective administration of a beta 2-agonist to horses with heaves using a compact inhalation device and metered-dose inhalers. The purpose of the study was to administer therapeutic aerosol generated by metered-dose inhalers to horses exhibiting clinical signs of heaves using a compact inhalation device developed for human medicine. It was fitted to a custom face mask in order to study the effect of an inhaled beta 2-agonist, fenoterol. Pulmonary function testing was performed on six horses following an acute exacerbation of heaves, characterized by tachypnea, wheezes, crackles, and spasmodic cough. Horses inhaled fenoterol in 1 mg increments administered as one 200 microgram puff every 5-10 s with the recording of da...
The airway response of horses with recurrent airway obstruction (heaves) to aerosol administration of ipratropium bromide. The airway response to aerosol administration of the anticholinergic agent ipratropium bromide was determined in 8 horses with recurrent airway obstruction (heaves). The reversibility of airway obstruction was confirmed by measuring lung function before and during stabling; and by determining the response to atropine administration (0.02 mg/kg bwt intravenously). The dose-response to ipratropium bromide was determined using a Williams square design experiment in which 25, 50 or 75 micrograms ipratropium bromide/ml (4 ml/100 kg bwt) or the same volume of vehicle was administered to each horse b...
In vitro effects of alpha 2-adrenergic receptor stimulation on cholinergic contractions of equine distal airways. In horses with noninduced, reversible airway obstruction (heaves), pulmonary function is improved after sedation with the alpha 2-adrenergic agonist xylazine. The mechanism of this effect is undetermined. Because the predominant excitatory innervation of equine airways is cholinergic, the influence of alpha 2-adrenergic receptor stimulation on the response of isolated distal airways to cholinergic stimulation was determined. Distal bronchial segments from 22 healthy horses were suspended in isolated organ baths where their mechanical responses to various stimuli could be studied. Each tissue w...
Adrenergic and peptidergic innervation of the trachealis muscle in the normal horse: a preliminary report. The tone of respiratory smooth muscle is largely determined by the input from autonomic nerves. The distribution of adrenergic and selected nonadrenergic, non-cholinergic (NANC) nerves in the normal equine trachealis muscle was investigated using immunohistochemistry. The smooth muscle of the trachealis was found to contain numerous nerves immunoreactive for an enzymatic marker of adrenergic nerves, as well as many nerves immunoreactive for a putative NANC neurotransmitter, peptide histidine isoleucine, a potent bronchodilator. The tissue surrounding the respiratory smooth muscle contained num...
Flunixin meglumine blocks frusemide-induced bronchodilation in horses with chronic obstructive pulmonary disease. Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg ...