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Summary Reasons for performing study Particle mapping within stalls has demonstrated a relationship between particulate concentrations and visible accumulations of tracheal mucus. However, measurement of breathing zone particulate concentrations, which is the most accurate way to measure exposure, has not been performed to determine the relationship between exposures and accumulations of tracheal mucus sufficient to affect performance. Objectives To compare breathing zone particulate exposures between horses with tracheal mucus scores (MS) previously demonstrated to affect performance (MS≥2) and those without (MS = 0) visible tracheal mucus. Study design Case–control study. Methods We endoscopically examined 649 Thoroughbred racehorses over 7 months and selected 113 age-matched cases and controls based on the presence (MS≥2) or absence (MS = 0) of tracheal mucus, respectively. Inflammatory cell numbers in tracheal lavage were also determined. Breathing zone monitors recorded particulate exposure during 3 time periods (mid-day, evening and overnight). Total recording time averaged 17.5 h/horse. Results The overall prevalence of MS≥2 in the observed stables was 23%. Breathing zone particular matter (PM10) concentrations were very similar to previously reported ambient concentrations. During the evening and overnight, cases had significantly higher breathing zone PM10 concentrations and neutrophil counts than controls. Inflammatory cell counts were associated with average PM10 concentrations throughout the day. Conclusions Breathing zone particulate concentrations are associated with MS≥2 and inflammatory cell numbers. If breathing zone particulate exposures are predominantly influenced by ambient PM concentrations, racing stable management practices to reduce particle exposures should greatly reduce the prevalence of tracheal mucus.

Summary Reasons for performing study Current diagnosis of recurrent laryngeal neuropathy (RLN) depends upon disease recognition in the clinically affected horse. Biopsy of the intrinsic laryngeal muscles may provide a method to identify the changes in fibre-type composition that occur in RLN before clinical signs become apparent. Objective To develop an ultrasound-guided biopsy technique of the left cricoarytenoideus lateralis muscle (CALM) and evaluate its efficacy and safety in vivo. Study design A longitudinal descriptive study. Methods Six standing horses underwent ultrasound-guided biopsy of the left CALM. Frozen muscle cores were obtained with a breast biopsy tool. Serial endoscopic, ultrasonographic and physical examinations before and for 8 weeks after the biopsy were assessed for iatrogenic trauma. Histologies of representative muscle core cross-sections were analysed for the total number of muscle fibres obtained with each biopsy. Results There were no immediate complications of the procedure and the left CALM was harvested in all instances. Biopsy samples had an average weight of 0.043 g (range = 0.023–0.077 g) and contained 3418 fibres in cross-section (range = 711–7143). Laryngeal endoscopic grade did not change significantly between prebiopsy and the end of the 8 week follow-up. The left CALM had significantly greater echogenicity than the right throughout the study (P

Summary Reason for performing study: Accumulations of tracheal mucus assessed by endoscopic examination are associated with poor performance in racehorses. The air quality in horses' stalls may contribute to this visible tracheal mucus. Objectives: To determine whether the concentration and number of airborne particulates in stalls are associated with visible accumulations of tracheal mucus and with the number of inflammatory cells in tracheal aspirates. Methods: We studied 107 racehorses from 3 stables, in 3 different months, and measured airborne particulate matter 3 times daily in each of the stalls. On each monthly visit, horse airways were examined endoscopically and assigned a mucus score, and tracheal lavage was performed. Bivariate procedures, general estimating equations and linear mixed models were applied to estimate the association between PM and the presence of accumulations of mucus and number of inflammatory cells. Results: Stable, stall, month and PM were all significantly associated with the presence of accumulations of tracheal mucus, which had an overall prevalence of 67%. The odds of horses having visible accumulation of mucus were increased when horses occupied enclosed stables or stalls with higher particulate concentrations, and when concentrations of larger particles (≤10 µm in diameter) were elevated. Sixty-eight percent of tracheal wash samples contained more than 20% neutrophils. Increased numbers of neutrophils were associated with the concentration of smaller particles (≤2.5 µm in diameter). Potential relevance: Careful consideration of stable construction and management practices focused on maintaining the lowest possible dust concentrations throughout the day should reduce the prevalence of visible accumulations of tracheal mucus, potentially improving racing performance.

Summary Although glucocorticoids have been used successfully for the treatment of noninfectious inflammatory diseases of horses for more than 35 years, their use has been attended by a fear of the induction of laminitis. This paper reviews the evidence for this fear and the possible mechanisms whereby glucocorticoids could participate in laminitis induction. Although the association of laminitis with elevated serum cortisol in pituitary pars intermedia dysfunction suggests that chronic exposure to glucocorticoids may be part of laminitis pathogenesis, review of published reports and databases suggests that glucocorticoid-induced laminitis is a relatively rare occurrence. However, several of the actions of glucocorticoids are similar to those known to be involved in laminitis pathogenesis. Glucocorticoid administration can induce insulin resistance, lead to vascular dysfunction that potentiates vasoconstriction, and interfere with keratinocyte proliferation and differentiation as well as matrix integrity, all mechanisms that could possibly induce laminitis. Drug formulation, dose and route of administration, and the systemic and hoof disease history of the horse must all be considered when assessing laminitis risk during glucocorticoid treatment. Generally, local glucocorticoid administration presents little risk as does systemic treatment of recurrent airway obstruction without concurrent disease. Caution should be used however in horses that are overweight and/or insulin resistant, or have had a recent bout of acute laminitis of alimentary or endotoxic origin. Overall, however, the risk of laminitis after glucocorticoid treatment, especially local use, is acceptable compared to the many benefits of these drugs.

REASONS FOR PERFORMING STUDY: Efficacy of medications for recurrent airway obstruction is typically tested using clinical, cytological and lung function examinations of severely affected animals. These trials are technically challenging and may not adequately reflect the spectrum of disease and owner complaints encountered in clinical practice. OBJECTIVE: To determine if owners of horses with chronic airway disease are better able to detect drug efficacy than a veterinarian who clinically examines horses infrequently. METHOD: In a double-blinded randomised controlled trial, owners and a veterinarian compared the efficacy of dexamethasone (0.1 mg/kg bwt per os, q. 24 h, for 3 weeks; n = 9) to placebo (n = 8) in horses with chronic airway disease. Before and after treatment, owners scored performance, breathing effort, coughing and nasal discharge using a visual analogue scale (VAS). The clinician recorded vital parameters, respiratory distress, auscultation findings, cough and nasal discharge, airway mucus score, bronchoalveolar lavage fluid (BALF) cytology and arterial blood gases. RESULTS: The VAS score improved significantly in dexamethasone- but not placebo-treated horses. In contrast, the clinician failed to differentiate between dexamethasone- and placebo-treated animals based on clinical observations, BALF cytology or endoscopic mucus score. Respiratory rate (RR) and arterial oxygen pressure (PaO(2)) improved with dexamethasone but not placebo. CONCLUSIONS AND CLINICAL RELEVANCE: In the design of clinical trials of airway disease treatments, more emphasis should be placed on owner-assessed VAS than on clinical, cytological and endoscopic observations made during brief examinations by a veterinarian. Quantifiable indicators reflecting lung function such as RR and PaO(2) provide a good assessment of drug efficacy.

Summary Reasons for performing the study: Exercise-induced pulmonary haemorrhage (EIPH) occurs in nearly all strenuously exercising horses. Recent studies have attempted to identify the role of free blood within the airspaces, in the lung fibrosis that develops within the lungs of EIPH horses. Hypothesis: Repeated exposure of the equine lung to autologous blood results in lung fibrosis similar to that observed in spontaneous EIPH. Methods: Forty ml of autologous blood from the jugular vein was instilled into preselected lung regions of 6 horses one, 2, 3, 4 or 5 times at 2 week intervals, with 40 ml of saline instilled into the contralateral lung serving as a control. The time interval between instillation of the first blood and euthanasia ranged from 2–10 weeks. The lung from each instillation site was harvested, and the histopathology was scored from each region based upon the presence and abundance of blood, haemosiderin and interstitial collagen. Consequently, at the time of euthanasia, the time since instillation of the first blood ranged from 2–10 weeks. Results: Beyond retention of blood, and the accumulation of haemosiderin, there was no visible increase in perivascular and interstitial collagen within the blood-instilled lung sites. In a small number of regions, there were foci of bronchiolitis obliterans organising pneumonia with collagen accumulation within these foci, but no collagen accumulation with the characteristic perivascular and interstitial histological distribution seen in EIPH. Conclusions: Free blood within the airways of horses does not result in a qualitative increase in the amount of interstitial collagen within 8–10 weeks, and is therefore an unlikely aetiological factor in the lung collagen accumulation that occurs in EIPH. Potential relevance: This study emphasises the efficiency of the equine lung in clearing blood from the airspaces. Further, it suggests that the aetiopathogenesis of EIPH is not driven by events within the airspace lumen, but rather emanates from within the vasculature and lung interstitium.

Summary We determined the effects of exercise induced concentrations of epinephrine (E) and norepinephrine (NE) on acetylcholine (ACh) release and smooth muscle contraction. To determine ACh release, trachealis strip bundles were suspended in 2 ml tissue baths in the presence of neostigmine (10−6M), guanethidine (10−5M) and atropine (10−7M), and stimulated by electrical field stimulation (EFS; 20 V, 0.5 ms, 0.5 Hz, for 15 min). EFS-induced ACh release was measured by high-performance liquid chromatography coupled with electrochemical detection. Concentration responses to E and NE (10−8 to 10−5M) were determined. In time-control tissues, ACh release averaged 8.2 ± 0.9 pmol/g/min. Epinephrine caused significant inhibition of ACh release at concentrations of 10−7M or greater and NE at 10−6M or greater. E- and NE-induced inhibition of ACh release was attenuated by the α2-adrenoceptor antagonist idazoxan (10−6 M) but not by the α2-antagonist prazosin (10−6M) nor the β-antagonist propranolol (10−6M). We determined if E and NE had inhibitory actions on smooth muscle by examining their effect on the ACh concentration-response curve of trachealis. E (10−6M) inhibited contraction only at 10−7M ACh, i.e. when muscle tension was low. NE had no effect. Exercise induced concentrations of E inhibit cholinergically mediated bronchospasm primarily by α2-mediated prejunctional inhibition of ACh release and, to a lesser degree, by a post junctional effect on airway smooth muscle. NE only inhibits ACh release but not significantly at the concentrations achieved during exercise.

Summary Exercise induced pulmonary haemorrhage (EIPH) is thought to result from capillary stress failure associated with high pulmonary vascular pressures during heavy exercise. One possible mechanism for the caudodorsal distribution of haemorrhage is preferential distribution of blood flow to affected regions due to regional differences in pulmonary vascular regulation. Endothelial cells (EC) are known controllers of vascular smooth muscle tone and could play a role in regional distribution of blood flow. The present study investigated relaxation responses to the endothelium-dependent and independent vasodilators, methacholine (MCh) and nitroglycerin (NTG) in pulmonary arteries from the caudodorsal (top) and cranioventral (bottom) regions of the lung. Pulmonary arteries (7 mm diameter) from 6 horses were isolated from top and bottom regions of the lung and vessels with and without endothelium were mounted in 15 ml tissue baths. Vessels were pre-contracted with norepinephrine (10−6 M) and changes in isometric tension in response to MCh (10−6 M) and NTG (10−6 M) were compared. MCh consistently relaxed, and never contracted, endothelium-intact top vessels. In top vessels, relaxation was abolished by removal of EC, suggesting an obligatory role of EC in MCh relaxation. However, in bottom vessels, a small transient relaxation was followed by a profound contraction, enhanced by EC removal. Relaxation to NTG was similar in all vessels. Therefore, in response to MCh, top vessels relax in an endothelium-dependent manner, while bottom vessels contract. Similar regional differences in endothelium dependent flow mediated vasodilation may result in higher blood flow to the caudodorsal regions of the lung and hence be responsible in part for the location of EIPH.

Summary Reasons for performing study: Although subclinical airway inflammation is thought to be common in horses, there is little information on its prevalence and none on risk factors. Objective: To determine the prevalence and risk factors for an increased number of inflammatory cells and for mucus accumulation in the trachea of pleasure horses. Methods: Horses (n = 266) in stables (n = 21) in Michigan were examined endoscopically, once in winter and once in summer 2004. Visible tracheal mucoid secretions were graded 0–5 and inflammatory cell numbers counted in a tracheal lavage sample. Information collected about each horse included age, gender, presence of cough, percent time indoors and source of roughage. The repeated measures were analysed by generalised estimating equations and linear mixed models. Results: Horses eating hay, especially from round bales, had the most neutrophils, whereas horses feeding from pasture had the fewest. Being female and being outdoors in winter were associated with increased numbers of inflammatory cells. Older horses had fewer macrophages than young horses. More than 70% of horses had >20% neutrophils in tracheal lavage. Twenty percent of horses had a mucus accumulation score >1; 17% had both a mucus score >1 and >20% neutrophils. The significant risk factors for mucus accumulation >1 were age >15 years, feeding on hay as compared to pasture, and being outdoors for more than 80% time in winter. Even though mucus accumulation score >1 was a risk factor for cough, only half of such horses coughed. Cough and mucus accumulation were associated with increased number of neutrophils. Conclusions: In comparison to pasture feeding, hay feeding, particularly from round bales, was associated with an increased number of neutrophils in the airway. Being outdoors in winter was associated with increased numbers of inflammatory cells and with mucus accumulation. Because 70% of horses have >20% neutrophils, this value should not be used as the sole indicator of airway inflammation. Potential relevance: The study reinforces the importance of hay feeding and older age as risk factors for inflammatory airway disease. Horses that do not have ‘heaves’ may be best kept indoors when winters are cold.

Summary Six normal, healthy horses age 3–10 years underwent left and right thoracoscopic examination using a rigid telescope. A minimum of 30 days was allowed between procedures. Horses were restrained in stocks and sedated with a continuous detomidine infusion. After surgical preparation of the hemithorax elected for surgery, and administration of local or regional anaesthesia of the surgery sites, thoracoscopy was completed during two 15 min pneumothorax periods. During the procedures, the thoracic structures were viewed using a 57 cm, 10 mm diameter, 30° rigid telescope connected to a digital camcorder to allow computer capture of digital images. The telescope was inserted into the thoracic cavity via 3 different intercostal spaces. The 8th, 10th and 12th intercostal spaces were randomly selected and used among horses. The exploration of each hemithorax started from the dorsal-caudal quadrant continued toward the cranial thorax and was completed by observing the diaphragmatic and caudal pulmonary region. Collapsed lung, aorta, oesophagus and diaphragm were viewed readily in either hemithorax. On exploration of the right hemithorax, the azygos vein, thoracic duct and pulmonary veins were also identified. Horses tolerated thoracoscopy well. Signs of discomfort, such as increased respiratory rate, coughing and decreased level of sedation, were associated with lung collapse in one horse, with pneumothorax on 2 occasions, and when the thorax was approached through the 8th intercostal space. Surgery performed via the 8th intercostal space was hindered by the rigidity of the 8th and 9th ribs, and by the presence of a greater musculature, which did not allow easy cranial and caudal movements of the telescope.

Summary Reasons for performing study: Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. Objectives: To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. Methods: Protocol 1 used 8 RAO-affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary function over 4 h. Protocol 2 used 6 similar horses to compare, in a crossover design, the effects of dexamethasone i.v. (0.1 mg/kg bwt), dexamethasone per os (0.164 mg/kg bwt) with and without prior fasting, and dexamethasone per os (0.082 mg/kg) with fasting. Results: Dexamethasone i.v. caused significant improvement in lung function within 2 h with a peak effect at 4–6 h. Dexamethasone per os was effective within 6 h with peak effect at 24 h at a dose of 0.164 mg/kg bwt prior to feeding. The duration of effect was, for all dexamethasone treatments, statistically significant for 30 h when compared to saline and tended to have a longer duration of effect when used orally. Dexamethasone per os at a dose of 0.164 mg/kg bwt to fed horses had mean effects comparable to dexamethasone at a dose of 0.082 mg/kg bwt per os given to fasted horses, indicating that feeding decreases bioavailability. Conclusions: Dexamethasone administered i.v. has a rapid onset of action in RAO-affected horses. Oral administration of a bioequivalent dose of the same solution to fasted horses is as effective as i.v. administration and tends to have longer duration of action. Fasting horses before oral administration of dexamethasone improves the efficacy of treatment. Potential relevance: Oral administration to fasted horses of a dexamethasone solution intended for i.v. use provides an effective treatment for RAO-affected animals.

Summary Reason for performing study: Accumulations of mucus within the trachea are often found during endoscopic examinations of the airways of poorly performing racehorses, but the clinical importance of this finding is unknown. Objectives: To determine the effect of tracheal mucus, pharyngeal lymphoid hyperplasia (PLH) and cytological indices of tracheal aspirate on racing performance in Thoroughbred horses assessed by race place and whether the horse was raced. Methods: Endoscopic examination of the nasopharynx, larynx and trachea was performed, and a tracheal aspirate obtained monthly at Thistledown racetrack from April to December, 2002 and 2003. Horses received a score of 0–4 for the degree of PLH and 0–4 for the amount of mucus visible in the trachea. The tracheal aspirate was assessed for turbidity, and total and differential cell counts. Generalised estimating equations models were used as repeated measures models for each risk factor and the level of association assessed through the risk factor's P value in the model. Results: Moderate to severe tracheal mucus (2–4) was a risk factor for poor racing performance. There was no association between degree of PLH, cell counts or turbidity of tracheal wash fluid and racing performance. However, horses that raced had higher total neutrophil counts in tracheal wash aspirates than horses that did not race. Conclusions: Grades 2–4 tracheal mucus should be considered a potential cause of poor racing performance in Thoroughbred horses. Clinical relevance: Because moderate to severe tracheal mucus accumulation, and not increased tracheal neutrophils, was a risk factor for poor racing performance, functionally significant airway inflammation may best be confirmed by the presence of mucus rather than increased number of neutrophils in the trachea.

Summary The goal of this study was to compare the rheological properties of mucus from horses with recurrent airway obstruction (RAO) to that from healthy controls during environmental challenge by stabling in stalls with straw as bedding and hay as feed. We determined viscoelasticity (log G*dyn/cm2, at 10 radian/s) and calculated mucociliary clearability index (MCI) and cough clearability index (CCI), which are derivative parameters of G*and the ratio of viscosity and elasticity measured at 1 and 100 radian/s, respectively. We also investigated the solids content of mucus, and cytology of bronchoalveolar lavage fluid (BALF). Samples were obtained before (0 h) and 6, 24 and 48 h after environmental challenge. The central findings were rheological changes in airway mucus, which occurred over time in RAO-affected animals, but not in controls. Mucus rheology was similar in both groups at 0 and 6 h. In RAO-affected horses, mucus viscoelasticity, as measured by log G*, increased from 2.49 ± 0.18 dyn/cm2(mean ± s.e.) at 0 h to 3.05 ± 0.13 dyn/cm2at 24 h after environmental challenge, and was accompanied by significant decreases in MCI and CCI. Percent solids of mucus did not differ significantly between the 2 groups, nor over time. Rheological values did not correlate with BALF cytology. We conclude that viscoelastic properties of tracheal mucus samples from RAO horses in remission do not differ from those of normal horses. However, environmental challenge causes clinical signs of small airway disease and a concurrent increase in mucus viscoelasticity only in RAO horses. Therefore, we infer that unfavourable changes in mucus rheology may contribute to stasis and accumulation of mucus in RAO horses in exacerbation, but not in clinical remission.

Summary Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function.

Summary Reasons for performing study: Laryngoplasty is the technique of choice for treatment of laryngeal hemiplegia, with the aim of improving airway function and/or eliminating respiratory noise. However, there are no quantitative data in the literature describing the effect of laryngoplasty on upper airway noise or its relationship to upper airway mechanics in horses with laryngeal hemiplegia. Objectives: To determine whether laryngoplasty reduces respiratory noise in exercising horses with laryngeal hemiplegia; and to establish whether the degree of upper airway obstruction can be predicted by upper airway noise, or the degree of arytenoid abduction correlated with airway obstruction and noise production. Methods: Six Standardbred horses with normal upper airways during maximal exercise were used. Respiratory sounds and inspiratory transupper airway pressure (Pui) were measured in all horses before and after induction of laryngeal hemiplegia and 30, 60 and 90 days after laryngoplasty. Inspiratory sound level (SL) and the sound intensity of the 3 inspiratory formants (F1, F2 and F3, respectively) were measured using a computer-based sound analysis programme. The degree of abduction was graded by endoscopic visualisation 1, 30, 60 and 90 days post operatively. Linear regression analysis was used to determine correlations between Pui, sound indices and grades of arytenoid abduction. Results: In laryngeal hemiplegia-affected horses, Pui, inspiratory SL and the sound intensity of F1, F2 and F3 were significantly increased. At 30 days following laryngoplasty, the sound intensity of F1 and Pui returned to baseline values. The sound intensities of F2, F3 and SL were significantly improved from laryngeal hemiplegia values at 30 days post operatively, but did not return to baseline at any measurement period. Sound level, F2 and F3 were significantly correlated with Pui (P

Summary Reasons for performing study: Acupuncture may be recommended for horses with ‘heaves’ because it is being increasingly applied to treat human asthma. Therefore, its efficacy was investigated in horses with this asthmalike disease. Objective: To evaluate the efficacy of a single acupuncture treatment for the relief of airway obstruction in heaves-affected horses. Methods: The efficacy of a single acupuncture treatment was tested in 10 heaves-affected horses, and the effect of removal from the dusty stall environment in 5 heaves-affected horses. Before treatment, horses were stabled to induce airway obstruction and, apart from trips to the laboratory for pulmonary function measurements, they remained stabled for the duration of each treatment. The severity of airway obstruction was quantified by measurement of lung function before treatment (baseline), and at 20, 60, 120 and 240 mins and 24 h after the following treatments administered in random order: halter restraint and patting, a single acupuncture treatment by an experienced acupuncturist, and a single acupuncture treatment using predetermined points (recipe) by a veterinarian with no acupuncture training. In a second study, horses were untreated and remained either in their stall or in a paddock for all measurements of lung function, after baseline readings were made. Results: In the first study, after all treatments, there was a temporal improvement in maximal change in pleural pressure, pulmonary resistance, dynamic compliance, respiratory rate, and tidal volume that lasted less than 24 h. There was no specific effect of acupuncture treatment. In the second study, removal from the dusty environment did not produce an improvement in lung function in the first 6 h. We conclude that most of the improvements in lung function observed in the study were due to handling. Conclusions: Assessed objectively, a single acupuncture treatment during an attack of heaves causes no more improvement in lung function than does handling the horse. Potential relevance: Acupuncture should not replace conventional medical treatments for heaves.

Summary Reasons for performing study: Guidelines for administration of oxygen to standing horses are unavailable because previous investigations of the efficacy of oxygen administration to increase arterial oxygenation in standing horses have produced equivocal results. Objective: To determine the eff ect of nasal oxygen supplementation on inspired and arterial blood gas tensions in control horses and those with moderate to severe recurrent airway obstruction (RAO). Methods: Normal horses (n = 6) and horses during an attack of RAO induced by stabling (n = 6) were studied. Oxygen was administered through either one or 2 cannulae, passed via the nares into the nasopharynx to the level of the medial canthus of each eye. Intratracheal inspired oxygen and carbon dioxide concentration and arterial blood gas tensions were measured at baseline and during delivery of 5, 10, 15, 20 and 30 l/min oxygen. Results: Nasal can nulae and all but the highest oxy gen flow rates were well tolerated. Fractional inspired oxygen concentration (FIO2) increased with flow but was significantly lower at all flow rates in horses with RAO compared with controls. Arterial oxygen tension (PaO2) was significantly increased (P

Background: Efficacy of inhaled fluticasone propionate (FP) for management of recurrent airway obstruction (RAO) has only been evaluated after several weeks' treatment. Objectives: To compare efficacy of (1) 3-day treatments with FP to dexamethasone (DEX) for management of RAO; and (2) FP and DEX to no treatment in prevention of acute RAO exacerbations. Animals: Nine RAO affected horses. Methods: Crossover studies in RAO-affected horses compared (a) 3-day treatment of RAO exacerbation with FP (3 and 6 mg q12h) and DEX (0.1 mg/kg q24h) and (b) FP (6 mg q12h) and DEX (0.1 mg/kg q24h) to no treatment for prevention of acute exacerbations of RAO. Treatment efficacy and unwanted effects were judged from maximal change in pleural pressure (ΔPplmax), serum cortisol (COR), bronchoalveolar lavage (BAL) cytology, and subjective scores for respiratory distress and lameness. Results: In treatment trial, DEX and FP (6 mg) significantly decreased ΔPplmax by 48 and 72 hours, respectively; FP (3 mg) had no significant effect. DEX decreased COR more than did FP. In prevention trial, both DEX and FP (6 mg) prevented the increase in ΔPplmax that occurred in untreated horses. Both treatments decreased COR to the same degree. FP and DEX had no effects on bronchoalveolar lavage fluid (BALF) cytology and there was no evidence of laminitis. Conclusions and Clinical Importance: FP (6 mg q12h) is as effective as DEX for prevention of acute exacerbations of RAO and lower doses should be evaluated. High-dose FP is not as effective as DEX for treatment of RAO exacerbations.

Summary Reasons for performing study: Exercise-induced pulmonary haemorrhage (EIPH) occurs in the majority of horses performing strenuous exercise. Associated pulmonary lesions include alveolar and airway wall fibrosis, which may enhance the severity of EIPH. Further work is required to understand the pulmonary response to blood in the equine airways. Objectives: To confirm that a single instillation of autologous blood into horse airways is associated with alveolar wall fibrosis, and to determine if blood in the airways is also associated with peribronchiolar fibrosis. Methods: Paired regions of each lung were inoculated with blood or saline at 14 and 7 days, and 48, 24 and 6 h before euthanasia. Resulting lesions were described histologically and alveolar and airway wall collagen was quantified. Results: The main lesion observed on histology was hypertrophy and hyperplasia of type II pneumocytes at 7 days after blood instillation. This lesion was no longer present at 14 days. There were no significant effects of lung region, treatment (saline or autologous blood instillation), nor significant treatment-time interactions in the amount of collagen in the interstitium or in the peribronchial regions. Conclusion: A single instillation of autologous blood in lung regions is not associated with pulmonary fibrosis. Potential relevance: Pulmonary fibrosis and lung remodelling, characteristic of EIPH, are important because these lesions may enhance the severity of bleeding during exercise. A single instillation of autologous blood in the airspaces of the lung is not associated with pulmonary fibrosis. Therefore the pulmonary fibrosis described in EIPH must have other causes, such as repetitive bleeds, or the presence of blood in the pulmonary interstitium in addition to the airspaces. Prevention of pulmonary fibrosis through therapeutic intervention requires a better understanding of these mechanisms.

REASONS FOR PERFORMING STUDY: Although endoscopic scoring of the tracheal septum thickness is used as a diagnostic tool for evaluation of lower airway disease, its clinical relevance and reliability have never been critically assessed in the horse. OBJECTIVES: To investigate if septum thickness scores (STS) are reliable and serve as a clinically useful indicator of lower airway disease status and/or inflammation. METHODS: The variance of STS attributable to the horse, observer and changes over time was determined. The distribution of STS in a population of clinically normal horses and correlations of STS with age, gender, as well as mucus accumulation and cell differentials of tracheobronchial secretions and bronchoalveolar lavage fluid were investigated. Effects of altered pulmonary ventilation, induced by different drugs, on STS were assessed. Finally, STS of horses affected with recurrent airway obstruction (RAO) were compared to those of clinically normal horses. RESULTS: Recorded STS showed excellent intra- and satisfactory interobserver agreement Established clinical, endoscopic and cytological measures of lower airway inflammation, i.e. mucus accumulation scores and airway neutrophilia, did not correlate with STS. In horses age > or = 10 years, septum scores were significantly higher (P = 0.022) than in younger horses. Septum thickness scores did not differ significantly between clinically normal and RAO-affected horses both in exacerbation and in remission. Horses with markedly increased breathing effort (i.e. with metacholine- or lobeline hydrochloride-challenge), often differed markedly (up to 1.9 scores), but the average of end-inspiratory and end-expiratory STS did not differ from baseline STS. CONCLUSIONS AND CLINICAL RELEVANCE: Endoscopic STS are a reproducible measure, but STS did not correlate with clinical, endoscopic and cytological findings indicative of RAO or inflammatory airway disease.

Summary Reasons for performing study: Recent studies have evaluated surgical techniques aimed at reducing noise and improving airway function in horses with recurrent laryngeal neuropathy (RLN). These techniques require general anaesthesia and are invasive. A minimally invasive transnasal surgical technique for treatment of RLN that may be employed in the standing, sedated horse would be advantageous. Objective: To determine whether unilateral laser-assisted ventriculocordectomy (LVC) improves upper airway function and reduces noise during inhalation in exercising horses with laryngeal hemiplegia (LH). Methods: Six Standardbred horses were used; respiratory sound and inspiratory transupper airway pressure (Pui) measured before and after induction of LH, and 60, 90 and 120 days after LVC. Inspiratory sound level (SL) and the sound intensities of formants 1, 2 and 3 (F1, F2 and F3, respectively), were measured using computer-based sound analysis programmes. In addition, upper airway endoscopy was performed at each time interval, at rest and during treadmill exercise. Results: In LH-affected horses, Pui, SL and the sound intensity of F2 and F3 were increased significantly from baseline values. At 60 days after LVC, Pui and SL had returned to baseline, and F2 and F3 values had improved partially compared to LH values. At 90 and 120 days, however, SL increased again to LH levels. Conclusions: LVC decreases LH-associated airway obstruction by 60 days after surgery, and reduces inspiratory noise but not as effectively as bilateral ventriculocordectomy. Potential relevance: LVC may be recommended as a treatment of LH, where reduction of upper airway obstruction and respiratory noise is desired and the owner wishes to avoid risks associated with a laryngotomy incision or general anaesthesia.

Recurrent airway obstruction (RAO) is a common condition in stabled horses characterised by small airway inflammation and obstruction following exposure of susceptible horses to mouldy hay and straw. The aim of the present study was to investigate whether lung tissue from horses with RAO contains higher numbers of IgE-protein positive (+) cells and mast cells compared to controls after mouldy hay challenge. Furthermore, mast cell subtypes in lung tissue were investigated. IgE+ cells were detected in most lung tissue samples but no significant differences between RAO-affected and control horses were found. In the wall of the bronchi and bronchioli of both RAO-affected and control horses, mainly chymase+ mast cells (MC C ) were present (85% in the bronchial wall and 77% in the wall of the bronchioli), while 73% of the mast cells (MC) around blood vessels were tryptase+ mast cells (MC T ). No double stained MCs were detected. RAO-affected horses had significantly more MC C than controls in the wall of the bronchi (median = 7.6 and 1.7 cell/mm 2 , respectively, P ≤ 0.05). They also showed a tendency for more MC C in the wall of the bronchioli than controls (median = 21 and 2.9 cells/mm 2 , respectively, P = 0.07) but there were no differences in MC T numbers. The data suggest an involvement of MC C in the pathogenesis of RAO. Independently of the clinical diagnosis, there was a significant relationship between high MC C numbers in the bronchial wall and lung fibrosis, suggesting that these MC C may be involved in tissue remodelling. Furthermore, high MC C numbers were also associated with increased infiltration with lymphocytes and neutrophils.

Summary Reasons for performing study In many inflammatory diseases plasma cortisol concentration (CORT) increases at the onset of acute inflammation, but the situation in recurrent airway obstruction (RAO) of horses is unknown. Study design Split-plot repeated measures design with one grouping factor (disease) and two repeated factors (day and 3-hour intervals). Objective To test the hypothesis that CORT increases as acute exacerbations of RAO develop. Methods Four RAO-susceptible and 4 control horses were placed in a low dust environment (LDEnv) for 2 days followed by 2 days in a high dust environment (HDEnv). Exacerbations of RAO were indicated by increases in maximal change in pleural pressure (ΔPplmax) and decreases in breathing frequency variability (BFV), which was continuously measured by respiratory inductance plethysmography. Plasma samples for determination of CORT were collected every 6 h. Results In control horses, ΔPplmax and BFV were unaffected by the HDEnv, whereas in RAO-affected horses ΔPplmax increased and BFV decreased significantly. In the LDEnv, there was a circadian variation in CORT in both control and RAO-affected horses. In HDEnv, CORT was unaffected in control horses, but increased significantly in RAO-affected horses between 6 and 12 h after entering the HDEnv. Conclusions Plasma cortisol concentration increases concurrently with the development of acute exacerbations of RAO.

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 unequivocal identification and quantitation of clenbuterol in 2 mL of serum at concentrations as low as 10 pg/mL. Five horses were dosed with oral clenbuterol (0.8 microg/kg, BID) for 10 days, and serum was collected for 14 days thereafter. Serum clenbuterol showed mean trough concentrations of approximately 150 pg/mL. After the last dose on day 10, serum clenbuterol reached a peak of approximately 500 pg/mL and then declined with a half-life of approximately 7 h. Serum clenbuterol declined to 30 and 10 pg/mL at 48 and 72 h after dosing, respectively. By 96 h after dosing, the concentration was below 4 pg/mL, the limit of detection for this method. Compared with previous results obtained in parallel urinary experiments, the serum-based approach was more reliable and satisfactory for regulation of the use of clenbuterol. Clenbuterol (90 microg) was also administered intratracheally to five horses. Peak serum concentrations of approximately 230 pg/mL were detected 10 min after administration, dropping to approximately 50 pg/mL within 30 min and declining much more slowly thereafter. These observations suggest that intratracheal administration of clenbuterol shortly before race time can be detected with this serum test. Traditionally, equine drug testing has been dependent on urine testing because of the small volume of serum samples and the low concentrations of drugs found therein. Using LC-MS-MS testing, it is now possible to unequivocally identify and quantitate low concentrations (10 pg/mL) of drugs in serum. Based on the utility of this approach, the speed with which new tests can be developed, and the confidence with which the findings can be applied in the forensic situation, this approach offers considerable scientific and regulatory advantages over more traditional urine testing approaches.

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 analytical findings in urine in the presence and absence of furosemide. When administered intratracheally (90 microg/horse) to horses suffering from chronic obstructive pulmonary disease (COPD), clenbuterol had effects that were not significantly different from those of saline. In parallel experiments using a behavior chamber, no significant effects of IT clenbuterol on heart rate or spontaneous locomotor activity were observed. Clenbuterol concentrations in the urine were also measured after IT dose in the presence and absence of furosemide. Four horses were administered i.v. furosemide (5 mg/kg), and four horses were administered saline (5 mL). Two hours later, all horses were administrated clenbuterol (IT, 90 microg), and the furosemide-treated horses received a second dose of furosemide (2.5 mg/kg, i.v.). Three hours after clenbuterol dose (1 h after hypothetical 'post-time'), the mean specific gravity of urine samples from furosemide-treated horses was 1.024, well above the 1.010 concentration at which furosemide is considered to interfere with drug detection. There was no interference by furosemide with 'enhanced' ELISA screening of clenbuterol equivalents in extracted and concentrated samples. Similarly, furosemide had no effect on mass spectral identification or quantification of clenbuterol in these samples. These results suggest that the IT dose of clenbuterol (90 microg) is, in pharmacological terms, indistinguishable from the dose of saline, and that, using extracted samples, clenbuterol dose is readily detectable at 3 h after dosing. Furthermore, concomitant dose of furosemide does not interfere with detection or confirmation of clenbuterol.

Six healthy, awake, and pharmacologically restrained mature horses were studied in order to define the changes in cardiopulmonary function during and after exploratory thoracoscopy and to determine the presence of postoperative complications occurring 48 hours after thoracoscopy. In a randomised 3 x 3 latin square design with 2 replications, 18 procedures were performed: 6 right (RTH) and 6 left thoracoscopies (LTH) and 6 sham procedures (STH). Prior to each procedure a physical examination and a bronchoalveolar lavage fluid analysis were performed. During thoracoscopy and sham protocols, horses were sedated with a continual drip of detomidine HCl and data were collected at 6 time intervals: T1 (baseline), T2 (10 min detomidine administration), T3 (first 15 min pneumothorax), T4 (5 min recovery from pneumothorax), T5 (second 15 min pneumothorax), and T6 (10 min recovery from the second pneumothorax and detomidine). An endoscopic thoracic examination was conducted during the 2 pneumothorax periods. An identical protocol was followed for sham procedures without surgery or pneumothorax. Data were analysed by ANOVA with time and surgical procedure as main factors. Physical examinations, thoracic radiography and ultrasound, CBC and bronchoalveolar lavage fluid analysis were performed 48 h after thoracoscopy. Heart rate, respiratory rate, and cardiac output decreased following detomidine administration. There was a trend for cardiac output to be lower during thoracoscopy. Mild systemic hypertension was associated with thoracoscopy although there was no effect on pulmonary arterial pressure. Total and pulmonary vascular resistances were increased following detomidine administration. Thoracoscopy caused a further increase in systemic and pulmonary vascular resistances especially during the second pneumothorax. Arterial O2 tension decreased following detomidine administration and was further decreased during the second pneumothorax period. PaO2 values were lower when thoracoscopy was performed on the left rather than the right hemithorax. No significant complications were found during the 48 h follow-up evaluation. A subclinical postoperative pneumothorax occurred in 2 horses, one of which had sustained a lung laceration by the trocar. Thoracoscopy performed in healthy, awake, and pharmacologically restrained horses did not have detrimental cardiopulmonary effects and did not cause postoperative complications within the first 48 h period.

Summary Autoradiography with [125I]-Bolton Hunter substance P ([I]-BHSP) was used to detect substance P binding sites in the equine lung. Specific [I]-BHSP binding sites were very dense over small bronchial vessels, tracheobronchial glands and airway epithelium in large and small airways. The density of [I]-BHSP binding sites over airway smooth muscle was much lower than in the preceding tissues. Competition with an excess of either a specific neurokinin 1 receptor agonist, or a specific neurokinin 2 receptor agonist indicated that most specific [I]-BHSP binding sites in the equine lung represent neurokinin 1 receptors. The receptor-mediated effects of substance P in the equine lung are most likely to involve regulation of vascular tone and airway secretions based upon the density of specific [I]-BHSP binding sites in these tissues. Activation of intrapulmonary afferent nerves containing Substance P by noxious stimuli such as inhaled allergens or irritants may lead to increased mucus secretion and decreased airway diameter due to vascular congestion.

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 increase in delta Pplmax was due to increases in RL, Edyn, and inspiratory and expiratory air flow rates. Further increases in delta Pplmax were due to continuing increases in Edyn and flow rates with little change in resistance. The increase in inspiratory flow rates was the result of a decrease in inspiratory time. The large increase in peak expiratory flow could not be explained by the small decrease in expiratory time and must therefore be due to a change in breathing strategy as delta Pplmax increased. Changes in air flow rates as well as changes in RL and Edyn must be considered as reasons for a change in delta Pplmax when evaluating horses with COPD.

To investigate the effects of changes in intracellular cAMP on α2-adrenoceptor (AR)-induced inhibition of airway acetylcholine (ACh) release, we examined the effects of the α2-AR agonist clonidine on electrical field stimulation-evoked ACh release from equine tracheal parasympathetic nerves before and after treatment with 8-bromo-cAMP or forskolin. We also tested whether charybdotoxin (ChTX)- or iberiotoxin (IBTX)-sensitive Ca2+-activated K+ channels mediate α2-AR-induced inhibition by examining the effect of clonidine in the absence and presence of ChTX or IBTX on ACh release. The amount of released ACh was measured by HPLC coupled with electrochemical detection. Clonidine (10−7 to 10−5 M) dose dependently inhibited ACh release before and after treatment with 8-bromo-cAMP (10−3 M) or forskolin (3 × 10−5M). ChTX and IBTX, both at the concentration of 5 × 10−7 M, significantly increased ACh release; however, they did not alter the magnitude of clonidine-induced inhibition. These results indicated that in equine tracheal parasympathetic nerves, α2-AR-induced inhibition of ACh release is via an intracellular cAMP-independent pathway. Activation of both ChTX- and IBTX-sensitive Ca2+-activated K+ channels inhibits the electrical field stimulation-evoked ACh release, but these channels are not involved in the α2-AR-induced inhibition of ACh release.

Tachykinins, of which substance P (SP) is the prototype, are neuropeptides which are widely distributed in the nervous systems. In the equine gut, SP is present in enteric nerves and is a powerful constrictor of enteric muscle; in other species, SP is also known to have potent vasodilatory and pro-inflammatory effects. The specific effects of SP are determined by the subtype of receptor present in the target tissue. There are 3 known subtypes of tachykinin receptors, distinguished by their relative affinities for SP and other tachykinins. The distribution of SP binding sites in the equine pelvic flexure was determined using 125I-Bolton Hunter SP (I-BHSP) autoradiography. Most I-BHSP binding sites were determined to be saturable and specific, therefore presumably representing tachykinin receptors. The greatest degree of I-BHSP binding occurred over very small vessels, and over the muscularis mucosae; I-BHSP binding was also intense over the circular muscle of the muscularis externa and mucosa, and present, although less intense, over the longitudinal muscle of the muscularis externa. Competition of I-BHSP with specific receptor agonists for binding sites in the equine pelvic flexure were used to determine the subtypes of tachykinin receptors present. The neurokinin-1 receptor subtype predominated in the equine pelvic flexure, followed by the neurokinin-3 receptor subtype.

Arachidonic acid (AA) metabolism was assessed in cultured alveolar macrophages (AM) obtained from newborn (9- and 23-day-old) and adult (2- and 6-yr-old) cattle. The AM were prelabeled in [3H]AA-containing medium and, thereafter, stimulated with either A-23187 or zymosan. The released radiolabeled AA metabolites were measured by high-performance liquid chromatography with on-line radiodetection. The results showed that, among different-aged cattle, the synthesis of total 5-lipoxygenase (5-LO) metabolites [leukotrienes (LT) B4, LTC4, LTD4, and 5-hydroxyeicosatetraenoic acid (5-HETE)] increased with age in spite of similar levels of phospholipase-catalyzed AA release. In response to A-23187 and zymosan, 5-LO metabolic capacity of adult cattle AM was approximately 4- and approximately 10-fold that of 9-day-old cattle AM, respectively. As 5-LO metabolic capacity increased, the release of prostaglandins and thromboxane tended to decrease. Immunoblot analysis showed that the steady-state expression of 5-LO and 5-lipoxygenase-activating protein (FLAP) also increased in an age-dependent manner. In newborn calves, AM do not produce great amounts of LTB4; this factor might contribute to insufficient polymorphonuclear leukocyte recruitment into the alveolar space and the high susceptibility to neonatal lung infection.

The role of emergency surgery for spinal cord or cauda equina compression secondary to extradural metastases is assessed in terms of functional outcome in 84 cases. The records of patients with proven malignant extradural spinal compression were reviewed retrospectively to determine the influence of emergency versus elective decompressive surgery on functional outcome. A greater proportion undergoing emergency surgery, rather than electively (within 24 h) on the next list showed functional improvement, with recovered mobility (61.5% vs 25%). Overall, 70% of patients were mobile postoperatively. The findings suggest that despite initial delays in referral, and even if the patient is incontinent and immobile, emergency spinal decompression is justified.

We determined the effects of isoproterenol (Iso) on parasympathetic neurotransmission in isolated equine trachealis strips by comparing the effects of Iso on the contractile response to electrical field stimulation (EFS) and acetylcholine (ACh), as well as by measuring EFS-induced ACh release. The interaction of Iso with muscarinic receptors and endogenous nitric oxide was also investigated. ACh release was measured by high-performance liquid chromatography with electrochemical detection. Iso (10(-7) M or greater) caused significantly more inhibition of EFS- than of ACh-induced contraction, an observation usually interpreted as evidence of prejunctional inhibition of ACh release. However, the latter conclusion was not supported by measurement of ACh release. Iso concentration dependently augmented ACh release, which was reversed by the beta 2-adrenoceptor antagonist ICI-118,551 but not by the beta 1-adrenoceptor antagonist CGP-20,712A. Our results indicate that activation of beta 2-adrenoceptors augments ACh release. Moreover, the comparison of inhibitory effects on EFS- and ACh-induced contraction does not provide correct information about the prejunctional actions of beta-agonists. ACh release was increased more by atropine (10(-7) M) than by Iso (10(-6) M), indicating the predominance of prejunctional inhibitory muscarinic autoreceptors over excitatory beta 2-adrenoceptors. Additionally, we found that inhibition of nitric oxide synthase by NG-nitro-L-arginine did not affect either the cholinergic contractile response or ACh release in both the absence and presence of Iso.

Four mechanisms that modulate airway smooth muscle function in normal horses were studied in the bronchi of horses affected by the airway obstructive disease heaves. Results were compared with data from historical controls studied by the same personnel in the same laboratory. Rings from the left cranial lobar bronchus (LB1) and small bronchi (5 mm OD) were suspended in muscle baths, and the isometric tension were measured. The inhibitory nonadrenergic noncholinergic (iNANC) function was studied in LB1. After the LB1 segments were pretreated with atropine and contracted with histamine, electrical field stimulation (EFS) induced little or no relaxation, indicating iNANC dysfunction in horses with heaves. Bronchi from animals with heaves were hyporesponsive to EFS and acetylcholine. Epithelial removal augmented the contractile response of small bronchi to acetylcholine more in animals with heaves than in control animals, indicating an enhanced function of epithelial-derived relaxing factor. In contrast, cyclooxygenase inhibition with meclofenamate (10(-6) M) increased the EFS-induced contraction of small bronchi less in affected horses than in control horses, suggesting a change in prostaglandin production in favor of excitatory prostanoids. We conclude that in the bronchi of horses with heaves; the iNANC function is defective, the response of smooth muscle to cholinergic activation is diminished, the production of epithelial-derived relaxing factor is enhanced, and the inhibitory function of prostanoids is reduced.

The efficacy of partial arytenoidectomy was assessed in 6 Standardbred horses, with surgically induced laryngeal hemiplegia, at rest (Period A) and during exercise at speeds corresponding to maximum heart rate (Period C) and 75% of maximum heart rate (Period B). Peak expiratory and inspiratory airflow rate (PEF and PIF), and expiratory and inspiratory transupper airway pressure (PUE and PUI) were measured and expiratory and inspiratory impedance (ZE and ZI) were calculated. Simultaneously, tidal breathing flow-volume loops (TBFVL) were acquired using a respiratory function computer. Indices derived from TBFVL included airflow rates at 50 and 25% of tidal volume (EF50, IF50, EF25, and IF25) and the ratios of expiratory to inspiratory flows. Measurements were made before left recurrent laryngeal neurectomy (baseline), 2 weeks after left recurrent laryngeal neurectomy (LRLN) and 16 weeks after left partial arytenoidectomy coupled with bilateral ventriculectomy (ARYT). After LRLN, during exercise Periods B and C, Z1 and the ratio of EF50/IF50 significantly increased and PIF, IF50 and IF25 significantly decreased from baseline values. At 16 weeks after ARYT, Z1 returned to baseline values during Periods B and C. Although PIF, IF50, IF25, PEF/PIF, and EF50/IF50 returned to baseline values during Period B, these indices remained significantly different from baseline measurements during Period C. After ARYT, TBFVL shapes from horses during Period C approached that seen at the baseline evaluation. Partial arytenoidectomy improved upper airway function in exercising horses with surgically induced left laryngeal hemiplegia, although qualitative and quantitative evaluation of TBFVLs suggested that some flow limitation remains at near maximal airflow rates. These results indicate that, although the procedure does not completely restore the upper airway to normal, partial arytenoidectomy is a viable treatment option for failed laryngoplasty and arytenoid chondropathy in the horse.

The distribution of inhibitory nerves and the mediator of the inhibitory nonadrenergic noncholinergic (iN-ANC) nervous system were investigated in smooth muscle preparations from seven regions of equine airways. In tissues incubated with atropine and precontracted with histamine, electrical field stimulation produced frequency-dependent relaxation, and the magnitude of the relaxation decreased from trachea to central bronchi and was absent in peripheral airways. The degree of relaxation in bronchi was not simply a function of bronchial size or generation. Propranolol inhibited part of the relaxation only in the cranial trachealis. After propranolol, NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, eliminated the remaining relaxation in all preparations. This effect was reversed by L-arginine, the NO precursor, but not by D-arginine. Exogenous NO concentration dependently relaxed trachealis. These results indicate that: 1) adrenergic innervation is limited to cranial trachealis, 2) iNANC nerves supply the trachea and central bronchi, and 3) NO mediates iNANC function.

To determine the presence and function of alpha 2-adrenoceptors on cholinergic nerves innervating horse airway smooth muscle, the effects of some alpha 2-adrenoceptor agents on contractions of and acetylcholine (ACh) release from equine airway smooth muscle preparations were studied. Muscle contractions were elicited by either electrical field stimulation (EFS) or exogenous ACh. ACh release was induced by EFS and measured by high-pressure liquid chromatography and electrochemical detection. The alpha 2-adrenoceptor agonists clonidine (10(-7) to 10(-5) M) and UK-14,304 (10(-8) to 10(-6) M) concentration dependently inhibited ACh release and the contractile response to EFS but not the response to exogenous ACh. This inhibition was attenuated by the alpha 2-adrenoceptor antagonists yohimbine and idazoxan but not by the alpha 1-adrenoceptor antagonist prazosin. These results indicate that alpha 2-adrenoceptors exist on cholinergic nerves innervating equine airway smooth muscle, and activation of these receptors inhibits cholinergic neurotransmission. The observation that yohimbine alone had little effect on the contractile response to EFS suggests that, under these experimental conditions, endogenous norepinephrine had no influence on tracheal cholinergic neurotransmission via prejunctional alpha 2-adrenoceptors.

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 by nebulisation. Lung function was measured before and 1 and 4 h after nebulisation. Vehicle had no effect on lung function. Ipratropium decreased the maximal change in pleural pressure during tidal breathing (delta Pplmax) and pulmonary resistance (RL) and increased dynamic compliance (Cdyn). At the 1 h measurement period, the effect on RL and Cdyn was dose-dependent. A separate experiment demonstrated that the duration of action of ipratropium was between 4 and 6 h.

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 tissues surrounding the respiratory smooth muscle contained numerous nerves immunoreactive for the neuropeptides substance P and calcitonin gene-related peptide, which can cause marked vasodilation and bronchoconstriction. The complex innervation of the equine trachea should be kept in mind when interpreting the results of physiological experiments.

Summary Airborne dust concentration (ADC) was measured in 2 different horse management systems using an Andersen cascade impactor in the box-stall, and a personal Marple cascade impactor attached to the halter to measure ADC in the breathing zone. The levels of aeroallergens implicated in chronic obstructive pulmonary disease were measured by radioallergosorbent-inhibition immunoassay. A conventional management system (System C) utilising hay feed and straw bedding, and a recommended environment (System R) utilising wood shaving bedding and a complete pelleted diet were studied. In the stall, total and respirable ADC (geometric mean) were significantly higher in System C (2.55 mg/m3; 0.44 mg/m3, respectively) than in System R (0.70 mg/m3; 0.20 mg/m3, respectively). In System C, the total and respirable ADC in the breathing zone (17.51 mg/m3; 9.28 mg/m3) were much higher than in the stall, but values in both regions were similar in System R (0.52 mg/m3; 0.30 mg/m3). Major aeroallergens were significantly higher in System C than in System R: Micropolyspora faeni (1423 ng/m3 and 705 ng/m3), Aspergillus fumigatus (1823 ng/m3 and 748 ng/m3), and mite allergens (1420 ng/m3 and 761 ng/m3). Measurement of ADC with personal samplers indicates that the very high inhalation challenge in the breathing zone is not reflected in measurements of stall air quality. When compared with System C, System R produced only 3% of the respirable dust burden in the breathing zone and a decreased aeroallergen challenge.