Endoscopic anatomy of the cervical vertebral canal in the horse: a cadaver study.

REASON FOR PERFORMING STUDY: Localisation of spinal cord compression in horses with cervical vertebral stenotic myelopathy is inexact. Vertebral canal endoscopy has been used in man to localise spinal cord lesions and has the potential to become a useful diagnostic technique in horses. OBJECTIVE: To establish a surgical approach via the atlanto-occipital space to the cervical vertebral canal in equine cadavers and describe the endoscopic anatomy of the cervical epidural and subarachnoid spaces. METHODS: The cadavers of 25 mature horses were used to assess 3 surgical methods to approach the cervical vertebral canal, including 2 minimally invasive and one open technique. Once the approach had been made, a flexible videoendoscope was inserted into the epidural space (epiduroscopy) or the subarachnoid space (myeloscopy) and advanced caudally until the intervertebral space between C7 and T1 was reached. RESULTS: The epidural and subarachnoid spaces could not be accessed reliably using the minimally invasive techniques. Furthermore, damage to the nervous tissues was a frequent complication with these procedures. The open approach allowed successful insertion of the videoendoscope into the epidural and subarachnoid spaces in all horses and no inadvertent damage was observed. Anatomical structures that could be seen in the epidural space included the dura mater, nerve roots, fat and the ventral internal vertebral venous plexus. In the subarachnoid space, the spinal cord, nerve roots, blood vessels, denticulate ligaments and external branch of the accessory nerve were seen. CONCLUSIONS: Using the open approach, epiduroscopy and myeloscopy over the entire length of the cervical vertebral canal are possible in the mature horse. POTENTIAL RELEVANCE: Cervical vertebral canal endoscopy may become a valuable tool to localise the site of spinal cord injury in horses with cervical vertebral stenotic myelopathy and could aid in the diagnosis of other diseases of the cervical spinal cord.

Repeated blood instillation into the airway of the horse does not cause pulmonary fibrosis.

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.

Effect of ventriculectomy versus ventriculocordectomy on upper airway noise in draught horses with recurrent laryngeal neuropathy.

REASONS FOR PERFORMING STUDY: Little is known about the efficacy of bilateral ventriculectomy (VE) or bilateral ventriculocordectomy (VCE) in draught horses. OBJECTIVES: To compare the effect of VE and VCE on upper airway noise in draught horses with recurrent laryngeal neuropathy (RLN) by use of quantitative sound analysis techniques. HYPOTHESIS: In competitive draught horses with grade 4 RLN, VE and VCE reduce upper airway noise during exercise, but VCE is more effective. METHODS: Thirty competitive hitch or pulling draught horses with grade 4 RLN were evaluated for upper airway sound during exercise. Respiratory rate (RR), inspiratory (Ti) and expiratory time (Te), the ratio between Ti and Te (Ti/Te), inspiratory (Sli) and expiratory sound levels (Sle), the ratio between Sli and Sle (Sli/Sle), and peak sound intensity of the second formant (F2) were calculated. Eleven horses were treated with VE and 19 with VCE. After 90 days of voice and physical rest and 30 days of work, the horses returned for post operative upper airway sound evaluation and resting videoendoscopy. RESULTS: VE significantly reduced Ti/Te, Sli, Sli/Sle and the sound intensity of F2. Respiratory rate, Ti, Te and Sle were unaffected by VE. VCE significantly reduced Ti/Te, Ti, Te, Sli, Sli/Sle and the sound intensity of F2, while RR and Sle were unaffected. The reduction in sound intensity of F2 following VCE was significantly greater than following VE. After VE and VCE, 7/11 (64%) and 15/18 (83%) owners, respectively, concluded that the surgery improved upper airway sound in their horses sufficiently for successful competition. CONCLUSIONS: VE and VCE significantly reduce upper airway noise and indices of airway obstruction in draught horses with RLN, but VCE is more effective than VE. The procedures have few post operative complications. POTENTIAL RELEVANCE: VCE is recommended as the preferred treatment for RLN in draught horses. Further studies are required to evaluate the longevity of the procedure's results.

Expression of toll-like receptor 2 mRNA in bronchial epithelial cells is not induced in RAO-affected horses.

REASONS FOR PERFORMING STUDY: Airway inflammation in recurrent airway obstruction (RAO) is triggered by housing affected horses in stables.It has been suggested that RAO is an allergic condition, but innate immune mechanisms are also involved. Fungal products activate innate immune mechanisms through toll-like receptor 2 (TLR2). In human airway epithelium, TLR2 activation leads to interleukin (IL)-8 production. This pathway is negatively regulated by the zinc finger protein A20. This study was performed to enhance understanding of innate immune mechanisms in RAO. HYPOTHESIS: TLR2 and IL-8 mRNA are elevated in RAO during stabling compared with controls. A20 mRNA is negatively associated with the numbers of airway inflammatory cells. OBJECTIVES: To determine TLR2, IL-8 and A20 mRNA expression in lungs of stabled and pastured RAO-affected and control horses. METHODS: Airway obstruction and inflammatory cell counts in bronchoalveolar lavage were measured, and TLR2, IL-8 and A20 mRNA expression quantified by qRT-PCR in 6 RAO-affected and 6 control horses, during and after exposure to hay and straw. RESULTS: Airway obstruction and neutrophils were increased in RAO-affected horses during stabling. While stabling increased IL-8, TLR2 and A20 mRNA were unaffected. TLR2 and A20 were significantly correlated (r = 0.83) and A20 mRNA was negatively associated with inflammatory cells. POTENTIAL RELEVANCE: Stabling does not lead to an increase in TLR2 expression. Other molecules or processes in the TLR2 cascade might be important in fungal-induced airway inflammation. Equine epithelial-derived A20 may be involved in modulation of airway inflammation.

Regional distribution of collagen and haemosiderin in the lungs of horses with exercise-induced pulmonary haemorrhage.

REASONS FOR PERFORMING STUDY: Regional veno-occlusive remodelling of pulmonary veins in EIPH-affected horses, suggests that pulmonary veins may be central to pathogenesis. The current study quantified site-specific changes in vein walls, collagen and haemosiderin accumulation, and pleural vascular profiles in the lungs of horses suffering EIPH. HYPOTHESIS: In the caudodorsal lung regions of EIPH-affected horses, there is veno-occlusive remodelling with haemosiderosis, angiogenesis and fibrosis of the interstitium, interlobular septa and pleura. METHODS: Morphometric methods were used to analyse the distribution and accumulation of pulmonary collagen and haemosiderin, and to count pleural vascular profiles in the lungs of 5 EIPH-affected and 2 control horses. RESULTS: Vein wall thickness was greatest in the dorsocaudal lung and significantly correlated with haemosiderin accumulation. Increased venous, interstitial, pleural and septal collagen; lung haemosiderin; and pleural vascular profiles occurred together and changes were most pronounced in the dorsocaudal lung. Further, haemosiderin accumulation colocalised with decreased pulmonary vein lumen size. Vein wall thickening, haemosiderin accumulation and histological score were highly correlated and these changes occurred only in the caudodorsal part of the lung. CONCLUSION: The colocalisation of these changes suggests that regional (caudodorsal) venous remodelling plays an important role in the pathogenesis of EIPH. POTENTIAL RELEVANCE: The results support the hypothesis that repeated bouts of venous hypertension during strenuous exercise cause regional vein wall remodelling and collagen accumulation, venous occlusion and pulmonary capillary hypertension. Subjected to these high pressures, there is capillary stress failure, bleeding, haemosiderin accumulation and, subsequently, lung fibrosis.

Effect of magnitude and direction of force on laryngeal abduction: implications for the nerve-muscle pedicle graft technique.

REASONS FOR PERFORMING STUDY: The nerve-muscle pedicle graft technique is a treatment for recurrent laryngeal neuropathy (RLN), but the optimal placement of the pedicles within the cricoarytenoideus dorsalis (CAD) muscle is unknown. HYPOTHESIS: The magnitude and direction of force placed on the muscular process of the left arytenoid cartilage affects the magnitude of laryngeal abduction. METHODS: Five larynges were harvested from cadavers. Using increments of 0.98 N, a dead-weight force generator applied a force of 0-14.7 N for 1 min each to the left muscular process at 0, 10, 20, 30, 40, 50, 60 and 70 degrees angles. The rima glottis was photographed digitally 1 min after each force had been applied. Distances between biomarkers (Lines 1-4) and right to left angle quotient (RLQ) were used to assess the degree of left arytenoid abduction. RESULTS: Increasing force from 0-14.7 N progressively and significantly increased the length of all lines and RLQ, indicating abduction. Furthermore, there was a significant interaction between force and angles. Applying forces of 7.84 N or greater (Lines 2-4 and RLQ) or 11.76 N or greater (Line 1) at angles 0, 10, 20 and 30 degrees resulted in significantly greater abduction than applying the same forces at 40, 50, 60 and 70 degrees. Angles of 0-30 degrees correspond with the direction of pull exerted by the lateral compartment of the CAD muscle. CONCLUSION: In RLN, nerve-muscle pedicle grafts should be placed preferentially in the lateral rather than in the medial compartment of the CAD muscle. POTENTIAL RELEVANCE: The information presented can be used to assist surgeons in the planning and application of the nerve-muscle pedicle graft procedure.

Fluticasone propionate aerosol is more effective for prevention than treatment of recurrent airway obstruction.

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 (DeltaPpl(max)), 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 DeltaPpl(max) 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 DeltaPpl(max) 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.

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 (ElectroSpray Ionization, positive mode - Liquid Chromatography - Mass Spectrometry - Mass Spectrometry); with a Limit of Detection (LOD) estimated at 1 pg/mL. Following IV administration, TMQ plasma levels peaked at 1 min at 707 pg/mL, and at 9 min at 306 pg/mL following IT administration. Our results show that TMQ plasma concentrations decline rapidly following IV administration, which is consistent with the fast onset and short duration of TMQ effect that was observed in our previous studies. On the other hand, IT administration showed a very unique plasma concentration pattern. From a regulatory standpoint, the current available TMQ ELISA kit was also used in an attempt to detect TMQ from the plasma and urine samples. We report that the ELISA kit was unable to detect TMQ from any of the samples generated in these studies.

Electromyographic activity of the palatinus and palatopharyngeus muscles in exercising horses.

REASONS FOR PERFORMING STUDY: Determining the respiratory related activity of the palatinus and palatopharyngeus muscles in exercising horses is relevant because dysfunction of these muscles has been implicated in the pathogenesis of dorsal displacement of the soft palate. OBJECTIVE: To determine if the palatinus and palatopharyngeus muscles have respiratory activity that increases with intensity in exercising horses. METHODS: Electromyographic activity was measured in the palatinus and palatopharyngeus muscles using bipolar fine-wire electrodes while the horses completed an incremental exercise treadmill protocol. RESULTS: Both muscles displayed synchronous expiratory activity that increased significantly (P < 0.05) with exercise intensity. Phasic expiratory activity of the palatinus increased 390 +/- 98%, whereas phasic expiratory activity of the palatopharyngeus increased by 198 +/- 30% as the treadmill speed increased from 6 to 12 m/s. CONCLUSIONS: The palatinus and palatopharyngeus muscles may be important respiratory muscles, functioning to stabilise the position of the soft palate during intense exercise. CLINICAL RELEVANCE: The predominant expiratory activity of these muscles may be associated with specific muscle function related to exercise or distinct upper airway phenomena of an obligate nasal breather, such as the horse.

Histological evaluation of the equine larynx after unilateral laser-assisted ventriculocordectomy.

REASONS FOR PERFORMING STUDY: Trans-endoscopic laser surgery, such as unilateral laser-assisted ventriculocordectomy (LVC), has gained popularity in the treatment of RLN because a laryngotomy incision or general anaesthesia are not required. However, removal of the vocal fold and ventricle takes considerable laser energy and could cause collateral tissue damage, including injury to the adjacent laryngeal cartilages. OBJECTIVES: To document the histological effects of laser surgery on laryngeal tissues in horses that have undergone LVC for the treatment of laryngeal hemiplegia (LH). METHODS: Six horses were used: 4 with experimentally induced LH that had subsequently undergone LVC 6 months prior to euthanasia; and, 2 horses were used as controls. One of the control horses with naturally occurring LH was used to study the effect of neuropathy alone, whereas the other was subjected to euthanasia immediately following LVC to evaluate the acute effect of laser surgery. Using a band saw, each larynx was sectioned transversely at 5 mm intervals and evaluated histologically. RESULTS: Acutely, LVC caused thermal damage to adjacent soft tissues but did not affect the histology of the laryngeal cartilages. Six months after LVC, laryngeal cartilages were histologically normal and there was squamous metaplasia of the repaired laryngeal mucosa, resulting in restitution of the mucosal integrity. CONCLUSIONS: Using a diode laser in contact fashion at 20 W, LVC can be used to remove the laryngeal vocal fold and ventricle without causing laryngeal cartilage damage. POTENTIAL RELEVANCE: Laryngeal chondritis is an unlikely consequence of LVC.

Trimetoquinol: bronchodilator effects in horses with heaves following aerosolised and oral administration.

REASON FOR PERFORMING STUDY: The bronchodilator effects of trimetoquinol (TMQ) have been studied when administered i.v. or intratracheally, but not in an aerosolised form. OBJECTIVES: 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 pleural pressure (deltaPplmax) and heart rate (HR), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action of aerosolised (1000 pg/horse) and oral (6-60 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Aerosol administration of TMQ caused dose-dependent bronchodilation but did not change HR or cause other observable side effects. When 1000 microg/horse was administered via aerosol, TMQ produced a 2-phase bronchodilation; an immediate effect lasting up to 30 min and a second phase between 2 and 4 h. Oral TMQ was therapeutically ineffective. CONCLUSION: Aerosol administration of TMQ is a safe and effective method of producing bronchodilation in horses.

Pulmonary response to airway instillation of autologous blood in horses.

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.

Thermographic study of in vivo modulation of vascular responses to phenylephrine and endothelin-1 by dexamethasone in the horse.

REASONS FOR PERFORMING STUDY: In vitro, glucocorticoids potentiate vasoconstriction of equine digital vessels to catecholamines and this has been implicated as a mechanism of glucocorticoid-induced laminitis. This observation has never been confirmed in vivo. OBJECTIVES: To study the effects of glucocorticoid therapy on vasoconstrictor responsiveness in the horse in vivo. METHODS: In a blinded, randomised cross-over experiment, 9 horses were treated with either dexamethasone (0.1 mg/kg bwt i.v. q. 24 h) or saline i.v. for 6 days. The changes in local average skin temperature before (baseline) and after intradermal injections of the alpha1-adrenoceptor agonist phenylephrine (PHE; 10(-4), 10(-5), 10(-6), 10(-7) and 10(-8) mol/l), endothelin-1 (ET-1; 10(-5), 10(-6), 10(-7), 10(-8) and 10(-9) mol/l) or ET-1 plus a blocker (BQ-123 10(-6) mol/l; RES-701 10(-6) mol/l; and L-NAME 10(-4) mol/l) were investigated with a thermograph. RESULTS: Dexamethasone (DEX) decreased baseline skin temperatures, suggesting reduced blood flow as a consequence of an increase in vasomotor tone. This was accompanied by potentiation of the response to PHE as demonstrated by a left shift in the dose-response curve and a decrease in the EC50. Dexamethasone did not potentiate ET-1, but the interplay with the lower baseline temperature resulted in a significantly lower skin temperature for this vasoconstrictor after DEX. The different ET-1 blockers had no effect on ET-1 modulated skin temperatures. CONCLUSIONS: Dexamethasone decreases skin perfusion. This is accompanied by a potentiated alpha1-adrenoceptor agonist response and a greater response to ET-1. POTENTIAL RELEVANCE: Glucocorticoid therapy probably decreases perfusion of the equine hoof. During disease states that already are characterised by hypoperfusion and/or increased levels of circulating catecholamines, glucocorticoid therapy could, according to the vascular model of laminitis, tilt the balance in favour of laminitis.

Effects of unilateral laser-assisted ventriculocordectomy in horses with laryngeal hemiplegia.

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 (Fl, 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.

Airway inflammation in Michigan pleasure horses: prevalence and risk factors.

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.

Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with 'heaves'.

REASON FOR PERFORMING STUDY: 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'. OBJECTIVES: 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 pressure (deltaPplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 microg/kg bwt) and i.t. (2 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 microg/kg bwt, and was still increasing after administration of highest dose, 0.2 microg/kg bwt. Airway bronchodilation, measured as a decrease in deltaPplmax, also commenced at 0.01 microg/kg bwt. By the i.t. route, TMQ was 50-100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. CONCLUSION: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with 'heaves'. Further studies of TMQ by oral and aerosol routes are necessary. POTENTIAL RELEVANCE: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of 'heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other beta-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of 'heaves'.

Effect of tracheal mucus and tracheal cytology on racing performance in Thoroughbred racehorses.

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.

Electromyographic activity of the stylopharyngeus muscle in exercising horses.

REASONS FOR PERFORMING STUDY: There is a need to understand the process which leads to failure of recruitment of the stylopharyngeus muscle in clinical cases of nasopharygeal collapse. We therefore studied the timing and intensity of stylopharyngeus muscle activity during exercise in horses. OBJECTIVE: To measure the electromyographic (EMG) activity of the stylopharyngeus muscle in exercising horses and correlate it with the breathing pattern. METHODS: Five horses were equipped with a bipolar fine wire electrode placed on the stylopharyngeus muscle and a pharyngeal catheter. The horses exercised on a treadmill at speeds corresponding to 50 (HRmax50), 75 and 100% of maximum heart rate, and EMG activity of the stylopharyngeus muscle and upper airway pressures were recorded. The EMG activity of the stylopharyngeus muscle was then correlated to the breathing pattern and the activity quantified and reported as a percentage of the baseline activity measured at HRmax50. RESULTS: There was ongoing activity of the stylopharyngeus muscle throughout the breathing cycle; however, activity increased towards the end of expiration and peaked early during inspiration. Tonic activity was present during expiration. Peak, mean electrical and tonic EMG activity increased significantly (P<0.05) with exercise intensity. CONCLUSION: The stylopharyngeus muscle has inspiratory-related activity and tonic activity that increases with speed. POTENTIAL RELEVANCE: The stylopharyngeus muscle is one of a group of upper airway muscles that function to support and maintain the patency of the nasopharynx during inspiration. Failure of recruitment of the stylopharyngeus muscle during exercise is a potential explanation for clinical cases of dorsal pharyngeal collapse, but further work investigating the activity of the stylopharyngeus muscle in horses affected by this disease is needed.

Airborne particulates (PM10) and tracheal mucus: A case-control study at an American Thoroughbred racetrack.

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.

Regional differences in endothelial function in horse lungs: possible role in blood flow distribution?

We investigated regional differences of in vitro responses of pulmonary arteries (6-mm OD) from the dorsocaudal (top) and cranioventral (bottom) lung regions to endothelium-dependent vasodilators (methacholine, bradykinin, and calcium ionophore A-23187). Methacholine relaxed endothelium-intact top vessels; however, in bottom vessels, a small relaxation preceded a profound contraction. In top vessels, removal of endothelial cells converted relaxation to contraction, and in bottom vessels it abolished relaxation and enhanced contraction. Bradykinin and A-23187 were more potent and caused greater endothelium-mediated relaxation in top than in bottom arteries. The endothelium-independent vasodilator sodium nitroprusside caused similar relaxations in all rings. Nomega-nitro-L-arginine and NG-monomethyl-L-arginine and methylene blue abolished relaxation of top and bottom arteries to methacholine; meclofenamate had little effect. We conclude that regional differences in endothelium-mediated relaxation are caused by differences in the magnitude of the endothelial release of nitric oxide. Similar differences in endothelium-dependent flow-mediated vasodilation and endothelial nitric oxide release may result in preferential perfusion of caudodorsal lung regions.