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.
Efficacy of Inhaled Levalbuterol Compared to Albuterol in Horses with Recurrent Airway Obstruction. The (R)-enantiomer of racemic albuterol (levalbuterol) has bronchodilatory properties whereas the (S)-enantiomer causes adverse effects in human airways, animal models, and isolated equine bronchi. Levalbuterol is commercially available and improves pulmonary function of asthmatic patients with a longer duration of effect than albuterol. Objective: To determine the dose at which inhaled levalbuterol produces maximal bronchodilatory effect (EDmax) and determine its duration of action in recurrent airway obstruction (RAO)-affected horses in comparison to racemic albuterol. Methods: Nine horses w...
Pharmacokinetics of procaterol in thoroughbred horses. Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, ...
Rhabdomyolysis Secondary to Clenbuterol Use and Exercise. The literature regarding rhabdomyolysis secondary to illicit drug use is sparse. Clenbuterol is a bronchodilator approved for veterinary use, which in high doses can increase protein deposition and lipolysis similarly to anabolic steroids, and is thereby abused for bodybuilding and weight loss effects. Clenbuterol has previously been described in case reports to be cardiotoxic, with patient presentations similar to overdoses of sympathomimetic substances, but reports of rhabdomyolysis are limited to a single case series in horses. Methods: We report the first case of rhabdomyolysis secondary t...
Update on noninfectious inflammatory diseases of the lower airway. Inflammatory airway disease and recurrent airway obstruction are 2 nonseptic diseases of the equine respiratory system with a shared cause of exposure to particulate matter. They appear to occupy 2 ends of a spectrum of disease, but are differentiated by history, clinical signs, and response to treatment. Diagnosis can be made by sampling of respiratory fluids and lung function testing. Treatment consists of environmental modification and pharmacologic treatment with systemic or inhaled corticosteroids and bronchodilators.
Detection and pharmacokinetics of salbutamol in thoroughbred racehorses following inhaled administration. Salbutamol sulphate (Ventolin Evohaler) was administrated via the inhalation route to six horses at a dose of 0.5 mg every 4 h during the day for 2 days (total dose 4 mg). Urine and blood samples were taken up to 92 h postadministration. Hydrolyzed plasma and urine were extracted using solid phase extraction (SPE). A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification (LLOQ) for salbutamol of 10 pg/mL in plasma and urine. The parent drug was identified using UPLC-MS/MS. Most of the determined salbutamol plasma concentrations, post l...
Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways. Overexpression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform could contribute to airway bronchospasm by increasing the velocity of contraction. Whether the (+)insert isoform is present in the small airways and its expression is reversible in asthma are unknown. Objective: To determine the anatomical location and the expression kinetics of the (+)insert SMMHC isoform in airways of horses with heaves and to evaluate its modulation in response to disease status. Methods: We evaluated the (+)insert SMMHC isoform in the airways of horses with heaves during disease exacerbation a...
Technical and physiological determinants of airway smooth muscle mass in endobronchial biopsy samples of asthmatic horses. Morphometric analyses of endobronchial biopsies are commonly performed in asthma research but little is known about the technical and physiological parameters contributing to measurement variability. We investigated factors potentially affecting biopsy size, quality, and airway smooth muscle (ASM) content in heaves, an asthma-like disease of horses. Horses with heaves in clinical exacerbation (n = 6) or remission (n = 6) from the disease and six controls were studied using a crossover design. The effect of disease status, age, bronchodilation, biopsy forceps type, and carina size on total biop...
Use of a novel one-nostril mask-spacer device to evaluate airway hyperresponsiveness (AHR) in horses after chronic administration of albuterol. Inflammatory airway disease (IAD) is very common in stabled horses. Short-acting beta agonist (SABA) drugs are often used to relieve clinical signs, although long-term exposure to these drugs may result in rebound bronchoconstriction. The purpose of this study was twofold: i) to describe the deposition of radiolabeled drugs using a novel one-nostril design mask-spacer combination with a breath-activated inhaler (BAI), and ii) to determine whether treatment for 10 d with inhaled albuterol using this device would impair the ability of albuterol to prevent bronchospasm during a histamine challeng...
Owner-reported coughing and nasal discharge are associated with clinical findings, arterial oxygen tension, mucus score and bronchoprovocation in horses with recurrent airway obstruction in a field setting. In clinical practice, veterinarians often depend on owner-reported signs to assess the clinical course of horses with recurrent airway obstruction (RAO). Objective: To test whether owner-reported information on frequency of coughing and observation of nasal discharge are associated with clinical, cytological and bronchoprovocation findings in RAO-affected horses in nonstandardised field conditions. Methods: Cross-sectional study comparing healthy and RAO-affected horses. Methods: Twenty-eight healthy and 34 RAO-affected Swiss Warmblood horses were grouped according to owner-reported 'coughing ...
N-butylscopolammonium bromide causes fewer side effects than atropine when assessing bronchoconstriction reversibility in horses with heaves. Bronchospasm results in airway obstruction in horses with heaves. Atropine is the most potent bronchodilator drug currently available for horses, but is associated with side effects that limit its use. Like atropine, N-butylscopolammonium bromide (NBB) is an anticholinergic agent with bronchodilatory properties. Objective: To compare the bronchodilating effects and side effects of atropine and NBB in horses with heaves. Methods: Cross-over experiment using horses with heaves. Methods: Eight horses with heaves were administered atropine and NBB, using a cross-over design. Heart rate, pupillary ...
Effect of clenbuterol on tracheal mucociliary transport in horses undergoing simulated long-distance transportation. Pneumonia is observed in horses after long-distance transportation in association with confinement of head position leading to reduction in tracheal mucociliary clearance rate (TMCR). Objective: Clenbuterol, a beta-2 agonist shown to increase TMCR in the horse, will ameliorate the effects of a fixed elevated head position on large airway contamination and inflammation in a model of long-distance transportation model. Methods: Six adult horses. Methods: A cross-over designed prospective study. Horses were maintained with a fixed elevated head position for 48 hours to simulate long-distance tran...
Acid-base indicators in the venous and arterial blood of horses affected by recurrent airway obstruction (RAO). The acid-base equilibrium is closely linked to gas exchange in the lungs, and respiratory exchange ratios are used to evaluate respiratory effectiveness and tissue oxygen levels. Acid-base indicators are determined in both arterial and venous blood samples. This study compares the usefulness of acid-base indicators of venous and arterial blood in monitoring the condition of horses with recurrent airway obstruction. Prior to treatment involving bronchodilating glucocorticoids, expectorant and mucolytic drugs, more pronounced changes were observed in venous blood (pH 7.283, pCO2 61.92 mmHg, pO2 ...
Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse. Glucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO) in horses via systemic as well as local (inhalative) administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equi...
Effects of N-butylscopolammonium bromide on lung function in horses with recurrent airway obstruction. Equine recurrent airway obstruction (RAO) is characterized by airway inflammation, bronchoconstriction, and increased mucus production in the airways. Anticholinergic drugs like atropine induce bronchodilatation and rapid improvement in lung function. N-butylscopolammonium bromide (NBB) is an anticholinergic drug used to relieve spasmodic colic in horses, but its effect on airway smooth muscle is unknown. Objective: To evaluate the effect of NBB on clinical signs and lung function of RAO-affected horses. Methods: Nine horses diagnosed with RAO. Methods: Double-blind, placebo-controlled, random...
Bronchodilator activity of the selective muscarinic antagonist revatropate in horses with heaves. Bronchodilators are frequently used to attenuate airway obstruction in equine heaves (or recurrent airway obstruction). This study evaluated the selective (M(3) and M(1)) muscarinic antagonist revatropate, which offers potential advantages over non-specific antimuscarinic agents such as ipratropium. Protocol 1 assessed the response to inhaled revatropate (1, 2 and 7 mg) using a blinded, negative (inhaled saline) and positive (inhaled ipratropium bromide; 0.3, 0.7 and 2mg) controlled, dose escalation study, with six heaves horses. The lowest doses of revatropate and ipratropium induced a rapid ...
Effect of prolonged administration of clenbuterol on airway reactivity and sweating in horses with inflammatory airway disease. To determine whether prolonged administration of clenbuterol results in tachyphylaxis, specifically regarding its bronchoprotective properties and effect on sweating in horses. Methods: 8 Thoroughbreds with inflammatory airway disease. Methods: In a crossover design, horses received clenbuterol (0.8 μg/kg, p.o., q 12 h) or placebo for 21 days, with a washout period of ≥ 30 days between the 2 treatments. Airway reactivity was evaluated by use of flowmetric plethysmography and histamine broncho-provocation before (day 0; baseline) and every 7 days after the start of treatment. Sweat function ...
Clenbuterol toxicosis in three Quarter Horse racehorses after administration of a compounded product. 3 Quarter Horse racehorses were examined for suspected clenbuterol overdose 12 to 24 hours after administration by mouth of a compounded clenbuterol product. Results: All horses developed sinus tachycardia, muscle tremors, hyperhidrosis, and colic. Abnormalities on serum biochemical analysis included hyperglycemia, azotemia, and high creatine kinase activity. The presence of clenbuterol in the serum of all 3 horses and in the product administered was confirmed and quantified by use of liquid chromatography-electrospray tandem mass spectrometry. Results: Propranolol (0.01 mg/kg [0.005 mg/lb], I...
Comparative efficacy of inhaled albuterol between two hand-held delivery devices in horses with recurrent airway obstruction. Studies investigating the clinical efficacy of albuterol administered with the same propellant and commercially available delivery devices in horses with recurrent airway obstruction (RAO) are not currently available. Objective: To determine the efficacy of aerosolised albuterol administered to horses with RAO by means of 2 commercially available, hand-held delivery devices. Methods: Ten horses with RAO were kept in a dusty environment and fed mouldy hay to induce airway obstruction. Lung mechanics were measured before and after the procedure. ΔP(max) was measured 5 min after administration o...
Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi. Equine obstructive pulmonary disease, also known as heaves or recurrent airway obstruction (RAO) is a common equine pulmonary disease with some similarities to human asthma and COPD, which represents a major cause of morbidity and loss of lung performance. Salbutamol has been widely used for the treatment of human airway diseases and has usually been prepared as the racemic form of the drug. However, recently the R-enantiomer of salbutamol has been introduced into clinical practice in the treatment of asthma in humans and this has been suggested to be an improvement on the racemic form of the ...
Receptor-mediated enhancement of beta adrenergic drug activity by ascorbate in vitro and in vivo. Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. Objective: Extending this work to beta 2 adrenergic systems in vitro and in vivo. Methods: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuter...
Pharmacological studies of bronchial constriction inhibited by parasympatholytics and cilomilast using equine precision-cut lung slices. Equine precision cut lung slices (PCLS) were used to evaluate the ability of several pharmacologic compounds, parasympatholytics atropine, ipratropium, tiotropium and phosphodiesterase (PDE) 4-inhibitor cilomilast, to inhibit methacholine (MCh) induced bronchial constriction. The study war performed using vital lung samples from 20 horses, harvested immediately after euthanasia and lung examination.Tissue samples from the cranial, caudal and accessory lobe were taken for histological examination. Viability in PCLS of 250 +/- 20 microm was confirmed by observation of cilia movement and bronchia...
Plasma and urinary concentrations of trimetoquinol by LC-MS-MS following intravenous and intra-tracheal administration to horses with heaves. Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroS...
Clenbuterol and the horse revisited. Clenbuterol is a beta(2)-agonist and potent selective bronchodilator that is used to treat bronchospasm in the horse. The drug is normally administered to horses orally as a syrup formulation. Once absorbed into the systemic circulation, clenbuterol has the potential to cause many side effects, including a repartitioning effect and major alterations in cardiac and skeletal muscle function. Recent studies have also reported that clenbuterol can affect bone and the immune, endocrine and reproductive systems. A great deal of information has been published on the beneficial effects of short term t...
Equine recurrent airway obstruction and insect bite hypersensitivity: understanding the diseases and uncovering possible new therapeutic approaches. Recurrent airway obstruction (RAO) and insect bite hypersensitivity (IBH) are allergic conditions that are commonly encountered in the horse. Whilst complete allergen avoidance is an effective management strategy for both diseases, this may not be achievable in all cases and treatment options are therefore required. The inflammatory response is the main therapeutic target for glucocorticoids given to horses with RAO and severe cases of IBH, whilst the bronchodilators used in RAO primarily target airway smooth muscle. Such drugs are effective in most but not all individuals and there may be unw...
Trimetoquinol: bronchodilator effects in horses with heaves following aerosolised and oral administration. The bronchodilator effects of trimetoquinol (TMQ) have been studied when administered i.v. or intratracheally, but not in an aerosolised form. Objective: To define the relationship between the therapeutic and adverse responses (therapeutic index) of TMQ when administered as an aerosol or by the oral route. Methods: Increasing doses of TMQ were administered to horses with heaves as an aerosol and by the oral route. Dose ranged 100-1000 microg/horse for aerosolised TMQ and from 6-60 microg/kg bwt for the oral route. Airway and cardiac effects were assessed by measurement of maximal change in ple...
Effect of corticosteroid and bronchodilator therapy on bronchoalveolar lavage cytology following intrapulmonary blood inoculation. Intrapulmonary blood causes an inflammatory response. Modifying this inflammatory response may be useful in the treatment of exercise induced pulmonary haemorrhage (EIPH). Objective: To evaluate the efficacy of 3 treatments, an oral bronchodilator, inhaled steroid and oral steroid in modifying the cellular response to intrapulmonary blood inoculation. Methods: Experimental design was a randomised block divided into 4 experimental segments of 2 weeks. Eight normal horses were randomly assigned to pairs and treatments. Autologous blood was inoculated into the lungs on 4 occasions over an 8 week ...
Plethysmographic comparison of breathing pattern in heaves (recurrent airway obstruction) versus experimental bronchoconstriction or hyperpnea in horses. Horses with recurrent airway obstruction (heaves) are described as exhibiting "increased abdominal effort," but it is unknown whether this translates to an effective contribution to ventilation. Objective: We hypothesized that heaves is characterized by asynchrony between rib cage and abdominal motions, and that the abdominal component is the major contributor to ventilation. Methods: The rib cage versus abdominal motion in naturally occurring heaves (n = 15) was compared to controls at rest (n = 7) and during hyperpnea because of lobeline treatment, and the effects of histamine-induced bronch...