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.
Clenbuterol affects the expression of messenger RNA for interleukin 10 in peripheral leukocytes from horses challenged intrabronchially with lipopolysaccharides. On four occasions, four horses with heaves and four horses with small airway inflammatory diseases inhaled 0.9% saline based aerosol mixtures with or without lipopolysaccharides (LPS). Prior to the first saline and LPS inhalation, horses were untreated, while three and a half days prior to the third and forth inhalation horses had received 0.8 microg/kg clenbuterol intravenously twice daily. The messenger RNA (mRNA) expression of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-4, IL-6, IL-8, IL-10 and interferon- gamma (IFN- gamma) was investigated by RT-PCR, all of which ...
Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with ‘heaves’. Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. Objective: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural...
High throughput screening of sub-ppb levels of basic drugs in equine plasma by liquid chromatography-tandem mass spectrometry. This paper describes a high throughput LC-MS-MS method for the screening of 75 basic drugs in equine plasma at sub-ppb levels. The test scope covers diversified classes of drugs including some alpha- and beta-blockers, alpha- and beta-agonists, antihypotensives, antihypertensives, analgesics, antiarrhythmics, antidepressants, antidiabetics, antipsychotics, antiulcers, anxiolytics, bronchodilators, CNS stimulants, decongestants, sedatives, tranquilizers and vasodilators. A plasma sample was first deproteinated by addition of trichloroacetic acid. Basic drugs were then extracted by solid-phase e...
The effect of aerosolized and intravenously administered clenbuterol and aerosolized fluticasone propionate on horses challenged with Aspergillus fumigatus antigen. 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...
The anti-inflammatory effects of IV administered clenbuterol in horses with recurrent airway obstruction. Cyclic AMP elevating agents have been shown to exhibit anti-inflammatory properties in addition to functions such as bronchodilation. The aim of this study was to investigate this dual action of clenbuterol (CB; Ventipulmin) on horses affected with recurrent airway obstruction (RAO). Seven RAO susceptible horses received inhalation challenges with aerosolised lipopolysaccharide (LPS), hay dust suspension (HDS) and Aspergillus fumigatus antigen (AF) with and without prior treatment with intravenous CB. Data showed that CB exerted significant beneficial effects on lung function, total cell count...
Qualitative and quantitative evaluation of equine respiratory mechanics by impulse oscillometry. The long-established conventional reference technique (CRT) for measuring respiratory mechanics in horses lacks sensitivity and there is a need for further refinement in new technology, such as the impulse oscillometry system (IOS). Objective: To evaluate the potential use of the IOS as a clinical respiratory function test and compare it to the current CRT in horses suffering from common upper and lower airway dysfunctions. Methods: Six healthy horses were tested before and after induction of a unilateral nasal obstruction (UNO) or transient left laryngeal hemiplegia (LLH). Six heaves-affected...
Evaluation of cytokine production by equine alveolar macrophages exposed to lipopolysaccharide, Aspergillus fumigatus, and a suspension of hay dust. To evaluate cytokine production by equine alveolar macrophages after exposure to lipopolysaccharide (LPS), Aspergillus fumigatus, and hay dust, and determine the effect of clenbuterol on the cytokine response. Methods: 6 horses. Methods: Alveolar macrophages were exposed to PBS solution (negative control), LPS, hyphae and conidia of Aspergillus fumigatus (AF), or a suspension of hay dust (HDS) and incubated for 24 hours at 37 degrees C. Concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were measured in the supernatant. The procedure was repeated with cells that wer...
Treatment for a severe reaction to intravenous administration of diatrizoate in an anesthetized horse. A mature horse developed acute signs of bronchoconstriction causing hypoxemia and hypercapnia during anesthesia for computerized tomography of the maxillary sinus after i.v. administration of diatrizoate contrast medium. The horse was treated with aerosolized albuterol, atropine, and oxygen insufflation and recovered uneventfully despite severe hypoxemia and low hemoglobin saturation. The horse's condition continued to improve after treatment, and the horse was discharged with no further complications. Caution is advised with the use of contrast media in anesthetized horses.
Energetic cost of breathing, body composition, and pulmonary function in horses with recurrent airway obstruction. This study was conducted to determine whether horses with naturally occurring, severe chronic recurrent airway obstruction (RAO) 1). have a greater resting energy expenditure (REE) than control horses, 2). suffer body mass depletion, and 3). have significantly decreased REE after bronchodilation and, therefore, also 4). whether increased work of breathing contributes to the cachexia seen in some horses with RAO. Six RAO horses and six control horses underwent indirect calorimetric measures of REE and pulmonary function testing using the esophageal balloon-pneumotachograph method before and aft...
Therapeutic clenbuterol treatment does not alter Ca2+ sensitivity of permeabilized fast muscle fibres from exercise trained or untrained horses. Clenbuterol is a beta2-adrenoceptor agonist primarily used for treating bronchospasm and alleviating the symptoms of chronic obstructive pulmonary disease (COPD) in the horse. In other species (rats, mice, sheep, and cattle), chronic high doses of clenbuterol (typically in the milligram per kilogram body weight range) has been shown to cause a muscle directed protein anabolic response. Clenbuterol can also modify muscle fibre composition and therefore potentially affect muscle function. This has implications for the performance of exercising horses being treated with therapeutic doses of clenb...
Use of the impulse oscillometry system for testing pulmonary function during methacholine bronchoprovocation in horses. To compare sensitivity of the impulse oscillometry system (IOS) with that of the conventional reference technique (CRT; ie, esophageal balloon method) for pulmonary function testing in horses. Methods: 10 horses (4 healthy; 6 with recurrent airway obstruction [heaves] in remission). Methods: Healthy horses (group-A horses) and heaves-affected horses (group-B horses) were housed in a controlled environment. At each step of a methacholine bronchoprovocation test, threshold concentration (TC(2SD); results in a 2-fold increase in SD of a value) and sensitivity index (SI) were determined for respir...
Recurrent airway obstruction–heaves. Heaves, or recurrent airway obstruction (RAO), is a chronic respiratory disease featuring lower airway inflammation, bronchoconstriction, and mucus accumulation. Inhaled organic dusts and T helper 2 type immunologic reactions are involved in the complex pathophysiology of RAO. Clinical signs vary and alternate with remission periods. The diagnosis is often based on history and clinical examination in severe cases, but bronchoalveolar lavage may be useful for the detection of early cases. The most important aspect of treatment is to avoid exposure to allergens. Corticosteroids may be administer...
Effect of aerosolized albuterol sulfate on resting energy expenditure determined by use of open-flow indirect calorimetry in horses with recurrent airway obstruction. To evaluate effects of sedation on stability of resistance of the respiratory system (RRS) and measures of resting energy expenditure (REE) by use of open-flow indirect calorimetry (IC) and treatment with aerosolized albuterol on REE in horses with recurrent airway obstruction (RAO). Methods: 9 clinically normal horses and 8 horses with RAO. Methods: In phase 1, RRS was measured by using forced oscillometry (FOT) in 5 clinically normal horses before and after sedation with xylazine. In phase 2, REE was measured in 4 clinically normal horses between 20 and 25 minutes and again 35 to 40 minutes ...
Equine recurrent airway obstruction: pathogenesis, diagnosis, and patient management. Recurrent airway obstruction is a condition that affects some older horses maintained in confinement. Clinical signs range from exercise intolerance with occasional cough to dyspnea at rest. Bronchoalveolar lavage cytology is characterized by neutrophilic leukocytosis (15%-85%) and is recommended for making the diagnosis in horses with mild to moderate disease. Environmental management combined with periodic bronchodilator and antiinflammatory corticosteroid therapy yields the best prognosis for disease remission.
Innervation of equine airways. Equine obstructive pulmonary disease (COPD), or heaves or recurrent airway obstruction, is a common equine pulmonary disease similar to human asthma and/or CODP. Since bronchospasm and inflammation are the key features in heaves, the purpose of this paper is to review the contribution of neural mechanism that may be relevant to this disease. Equine airway receive cholinergic and adrenergic innervation, as well as observed in many species. It was suggested that the autonomic neural control in asthma might be defective with an imbalance between excitatory and inhibitory pathways, resulting in ex...
Comparison of serum and urinary concentrations of clenbuterol with and without concomitant administration of furosemide in horses. Furosemide is frequently used to control or prevent exercise-induced pulmonary hemorrhage in performance horses. The bronchodilating agent clenbuterol is also commonly used as a treatment for inflammatory airway disease in performance horses. Use of both medications is regulated by many racing authorities. The effects of concomitant administration of furosemide and clenbuterol on the pharmacokinetics of clenbuterol have not been well characterized. A study was designed to evaluate the influence of furosemide on serum and urine concentrations of clenbuterol after oral administration of clenbute...
Apparent ELISA detection times for albuterol after administration with the torpex equine inhaler device. Single doses of one, three, and six actuations (120 micro g albuterol/actuation) and multiple daily doses (six actuations per dose four times daily) for 5 days of aerosol albuterol sulfate were sequentially administered to each of six horses using an equine inhaler device (Torpex, 3M Animal Care Products, St. Paul, MN [corrected] and Boehringer Ingleheim Vetmedica, Inc., St. Joseph, MO [corrected]). A 2-week washout period was allowed between each dose. ELISA testing revealed no evidence of albuterol in urine at 24 hours after any single-dose administration. Results indicated that 48 hours or ...
Quantitative detection of salmeterol after inhalation in equine urine by liquid chromatography/tandem mass spectrometry. A sensitive, accurate and precise liquid chromatography/tandem mass spectrometry (LC/MS(2)) method was developed for the quantification of salmeterol in the urine of horses. The method consists of a liquid-liquid extraction with tert-butylmethyl ether and isopropanol at pH 12 after enzymatic hydrolysis. The extracts are analysed using an LC/MS system equipped with an electrospray ionisation (ESI) probe. Method validation showed excellent linearity, specificity, accuracy, precision and intra-laboratory repeatability and reproducibility. The limit of quantitative detection was 0.25 ng/mL and the...
[Influencing respiratory gas analytical lung function parameters by intravenous injection of clenbuterol in horses with chronic lung diseases]. In a placebo-controlled drug study data were collected about flow, volume and expiratory CO2-concentration in 13 horses with chronic obstructive pulmonary disease before and until 2.5 h after intravenous injection of clenbuterol. An ultrasonic flow measuring unit and an infrared-CO2-analyser (Spiroson Scientific) were used. functional deadspace and expiratory mixed volume were calculated. In addition the effect on the partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) in arterial blood was tested and the alveolo-arterial oxygen difference (AaDO2) determined. The volume of the functio...
Effects of inhaled ipratropium bromide on breathing mechanics and gas exchange in exercising horses with chronic obstructive pulmonary disease. Six Warmblood horses suffering an acute exacerbation of COPD were tested to investigate whether inhalation of ipratropium bromide (IB) dry powder (2,400 microg) 30 min preexercise would improve their exercise capacity. A cross-over protocol with an inert powder placebo (P) was used. Mechanics of breathing and arterial blood gases were determined before treatment, after treatment but pre-exercise, and during an incremental exercise test. Oxygen consumption (VO2) was also measured before and during exercise, and the time to fatigue recorded. Inhalation of IB reduced total pulmonary resistance (R...
Flowmetric comparison of respiratory inductance plethysmography and pneumotachography in horses. Respiratory inductance plethysmographic (RIP) and pneumotachographic (Pn) flows were compared dynamically in horses with bronchoconstriction. On a breath-by-breath basis, RIP was normalized to inspiratory volume from Pn, and peak [peak of subtracted final exhalation waveform (SFE(max))] and selected area [integral of subtracted final waveform during first 25% of exhaled volume (SFE(int))] differences between RIP and Pn flows during early expiration were measured in three settings: 1) healthy horses (n = 8) undergoing histamine bronchoprovocation; 2) horses with naturally occurring lower airway...
Anti-remodelling drugs for the treatment of asthma: requirement for animal models of airway wall remodelling. 1. Airway wall remodelling (AWR), the structural change induced by acute and chronic inflammation in the airways, may be one of the most significant and difficult to reverse components of progressive asthma. 2. The mechanisms underlying the development of AWR are not known. Studies of only the most superficial wall structures of large airways can be conducted in living humans because of the degree of invasiveness required to measure airway structural changes. These studies reveal that currently available agents do not fully prevent or reverse AWR. Thus, animal models of asthma pathology may be...
Efficacy of salmeterol xinafoate in horses with recurrent airway obstruction. To determine the onset, magnitude, and duration of bronchodilation after administration of aerosolized salmeterol xinafoate in horses with recurrent airway obstruction. Methods: Randomized controlled study Methods: 6 horses with recurrent airway obstruction. Procedure Horses received aerosolized salmeterol (210 microg) or no treatment, using a crossover design. Salmeterol was administered, using a mask designed for aerosol delivery in horses. Subjective rating of airway obstruction (RAO), maximal change in pleural pressure (deltaPplmax), and pulmonary resistance (RL) were determined at baselin...
Clenbuterol in the horse: confirmation and quantitation of serum clenbuterol by LC-MS-MS after oral and intratracheal administration. Clenbuterol is a beta2 agonist/antagonist bronchodilator, and its identification in post-race samples may lead to sanctions. The objective of this study was to develop a specific and highly sensitive serum quantitation method for clenbuterol that would allow effective regulatory control of this agent in horses. Therefore, clenbuterol-d9 was synthesized for use as an internal standard, an automated solid-phase extraction method was developed, and both were used in conjunction with a multiple reaction monitoring liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to allow unequivoca...
Effects of inhalation of albuterol sulphate, ipratroprium bromide and frusemide on breathing mechanics and gas exchange in healthy exercising horses. The possibility that pre-exercise inhalation of a bronchodilator by healthy horses could improve their mechanics of breathing and enhance performance was investigated. Ipratropium bromide (0.35 microg/kg bwt; n = 7) was administered by nebulisation 30 min before exercise and frusemide (1 mg/kg bwt; n = 6) was given in the same manner 2 h before exercise. Albuterol sulphate (360 and 720 microg; n = 7) were administered with a metered dose inhaler 2 h before exercise. Each drug was investigated independently of the others using cross-over protocols. Horses completed incremental exercise tests an...
Clenbuterol in the horse: urinary concentrations determined by ELISA and GC/MS after clinical doses. Clenbuterol is a beta2 agonist/antagonist bronchodilator marketed as Ventipulmin and is the only member of this group of drugs approved by the US Food and Drug Administration (FDA) for use in horses. Clenbuterol is a class 3 drug in the Association of Racing Commissioners International (ARCI) classification system; therefore, its identification in postrace samples may lead to sanctions. Recently, the sensitivity of postrace testing for clenbuterol has been substantially increased. The objective of this study was to determine the 'detection times' for clenbuterol after administration of an oral...
Intratracheal clenbuterol in the horse: its pharmacological efficacy and analytical detection. Clenbuterol, a beta2 agonist/antagonist, is the only bronchodilator approved by the US Food and Drug Administration for use in horses. The Association of Racing Commissioners International classifies clenbuterol as a class 3 agent, and, as such, its identification in post-race samples may lead to sanctions. Anecdotal reports suggest that clenbuterol may have been administered by intratracheal (IT) injection to obtain beneficial effects and avoid post-race detection. The objectives of this study were (1) to measure the pharmacological efficacy of IT dose of clenbuterol and (2) to determine the ...
Relationship between clinical signs and lung function in horses with recurrent airway obstruction (heaves) during a bronchodilator trial. During a trial to determine the dose response to the beta2-adrenergic agonist pirbuterol, we judged the severity of airway obstruction by use of a clinical scoring system and compared this to objective data obtained by quantitative measures of lung function. Six horses affected by recurrent airway obstruction were used in this trial. Four hundred and sixty-eight measurements of lung function and clinical scores were obtained from 13 measurement periods when horses received each of 6 doses of pirbuterol. Scores of 1-4 were assigned to degree of nasal flaring and abdominal effort and summed for ...
Pulmonary function and adrenal gland suppression with incremental doses of aerosolized beclomethasone dipropionate in horses with recurrent airway obstruction. To evaluate clinical response, pulmonary function, and adrenal gland response to incremental doses of beclomethasone dipropionate in horses with recurrent airway obstruction. Methods: Crossover trial. Methods: 8 horses with recurrent airway obstruction. Methods: Horses randomly assigned to 4 groups were treated twice daily via aerosol administration of placebo or 500, 1,000, or 1,500 micrograms of beclomethasone dipropionate in a crossover design with a 10-day minimum washout period. Subjective assessment of airway obstruction, serum cortisol concentration, and maximum change in pleural pressu...
A preliminary study of the effect of inhaled nitric oxide on lung mechanics in the standing horse with histamine-induced bronchoconstriction. The effect of inhaled nitric oxide on pulmonary mechanics was studied in normal standing horses with histamine-induced bronchoconstriction. The respiratory health status of 6 normal horses was established on the basis of history, clinical and bronchoalveolar lavage examination. Intrathoracic pressures were estimated using distal oesophageal pressures. Respiratory gas flows were measured using a heated pneumotachograph. Pulmonary mechanics variables were determined from these measurements on a breath by breath basis. Bronchoconstriction was induced by nebulizing a 0.75% w/v solution of histamin...