Efficacy of thermal cautery for intermittent dorsal displacement of the soft palate as compared to conservatively treated horses: results from 78 treadmill diagnosed horses.

REASONS FOR PERFORMING STUDY: Previously, objective comparisons of surgical procedures to relieve dorsal displacement of the soft palate (DDSP) have been limited by the presumptive basis of the diagnostic measures applied. OBJECTIVES: To assess and compare the efficacy of thermal cautery surgery to conservatively treated controls in racehorses definitively diagnosed with idiopathic intermittent DDSP. HYPOTHESIS: Both conservative and surgical treatments have a beneficial result on racing performance in racehorses affected with DDSP. METHODS: Race records were obtained for Thoroughbred racehorses definitively diagnosed with DDSP using high-speed treadmill endoscopy. Racing performance was assessed based on prize money won. RESULTS: Forty-eight horses that underwent thermal cautery and 30 conservatively treated controls were included. Pretreatment earnings significantly decreased in the race immediately prior to diagnosis. A high proportion of previously raced horses returned to racing after both treatments (90-96%). Intrahorse comparison of earnings in 3 races pre- vs. post treatment showed that 53% of conservatively treated horses and 36% of the thermal cautery group had improved performance. Although the difference between these 2 groups may be interpreted as being clinically significant, it was not statistically significant. CONCLUSIONS AND POTENTIAL RELEVANCE: A higher percentage of conservatively treated controls had improved individual performance compared to horses treated with thermal cautery. Thermal cautery appears less effective than other previously published surgical treatments for DDSP. Comparison of the 2 treatment methods should be interpreted cautiously because treatments were not randomised, resulting in baseline variability between groups.

Organic dust exposure increases mast cell tryptase in bronchoalveolar lavage fluid and airway epithelium of heaves horses.

BACKGROUND: Mast cell degranulation is believed to act as a key event in initiating and maintaining airway response to allergen challenge in human asthma. It is hypothesized that the mast cell may play a similar role in equine heaves, which shares many similarities with occupational dust-induced asthma. OBJECTIVE: The aim of this study was to quantify the mast cell proteinase tryptase in bronchoalveolar lavage fluid (BALF) from control and heaves-susceptible horses and to investigate tryptase mRNA and protein expression in pulmonary mast cells. METHODS: Equine BALF tryptase concentrations were determined by ELISA from control and heaves-susceptible horses pre and post 24 h hay/straw challenge (HSC). Tryptase mRNA and protein expression were investigated by quantitative PCR and immunohistochemistry in bronchial and bronchiolar tissue samples of control and heaves-susceptible horses. RESULTS: Both control and heaves-susceptible horses had significantly increased BALF tryptase concentrations following HSC (P=0.003 and 0.034, respectively). Increased numbers of tryptase-expressing intra-epithelial mast cells were demonstrated in heaves horses, but not controls, following challenge (P=0.02). Bronchiolar tissue from heaves horses removed from challenge contained significantly lower tryptase transcripts than that from control horses (P=0.02). CONCLUSION: Mast cell degranulation and tryptase release into the airways occur following HSC of control and heaves-susceptible horses. The greater number of mast cells available in the bronchiolar epithelium of heaves horses may be clinically significant in the pulmonary inflammatory response of heaves.

Comparison of the antioxidant status in tracheal and bronchoalveolar epithelial lining fluids in recurrent airway obstruction.

REASONS FOR PERFORMING STUDY: Following a period of airway inflammation the clearance of inflammatory cells along the mucociliary escalator may impose a considerable oxidant load on the trachea. OBJECTIVES: To determine the degree of oxidative stress in tracheal epithelial lining fluid (ELF) in comparison to that present in peripheral airways after an acute exposure to organic dust. METHODS: Tracheal wash fluid and bronchoalveolar lavage fluid (BALF) were collected for cytology and antioxidant analyses from 6 recurrent airway obstruction (RAO)-affected horses and 6 healthy control horses before and after stabling on straw bedding for 24 h. RESULTS: In RAO-affected horses, organic dust exposure resulted in a significant decrease in ascorbic acid concentration in tracheal ELF (P<0.0001), which was greater than the decrease in bronchoalveolar ELF (P = 0.0003). The percentage decrease in tracheal ELF ascorbic acid correlated with the percentage decrease in bronchoalveolar ELF ascorbic acid (r = 0.76; P = 0.004) following exposure. CONCLUSIONS: Acute organic dust exposure results in significant antioxidant depletion in the trachea, which may reflect inflammation and oxidative processes in peripheral airways. POTENTIAL RELEVANCE: Further work is required to evaluate the role of ascorbic acid depletion in the pathogenesis of RAO.

Recording of ECG signals on a portable MiniDisc recorder for time and frequency domain heart rate variability analysis.

Analysis of heart rate variability (HRV) is a non-invasive technique useful for investigating autonomic function in both humans and animals. It has been used for research into both behaviour and physiology. Commercial systems for human HRV analysis are expensive and may not have sufficient flexibility for appropriate analysis in animals. Some heart rate monitors have the facility to provide inter-beat interval (IBI), but verification following collection is not possible as only IBIs are recorded, and not the raw electrocardiogram (ECG) signal. Computer-based data acquisition and analysis systems such as Po-Ne-Mah and Biopac offer greater flexibility and control but have limited portability. Many laboratories and veterinary surgeons have access to ECG machines but do not have equipment to record ECG signals for further analysis. The aim of the present study was to determine whether suitable HRV data could be obtained from ECG signals recorded onto a MiniDisc (MD) and subsequently digitised and analysed using a commercial data acquisition and analysis package. ECG signals were obtained from six Thoroughbred horses by telemetry. A split BNC connecter was used to allow simultaneous digitisation of analogue output from the ECG receiver unit by a computerised data acquisition system (Po-Ne-Mah) and MiniDisc player (MZ-N710, Sony). Following recording, data were played back from the MiniDisc into the same input channel of the data acquisition system as previously used to record the direct ECG. All data were digitised at a sampling rate of 500 Hz. IBI data were analysed in both time and frequency domains and comparisons between direct recorded and MiniDisc data were made using Bland-Altman analysis. Despite some changes in ECG morphology due to loss of low frequency content (primarily below 5 Hz) following MiniDisc recording, there was minimal difference in IBI or time or frequency domain analysis between the two recording methods. The MiniDisc offers a cost-effective approach to intermediate recording of ECG signals for subsequent HRV analysis and also provides greater flexibility than use of human Holter systems.

Risk factors for epistaxis on British racecourses: evidence for locomotory impact-induced trauma contributing to the aetiology of exercise-induced pulmonary haemorrhage.

REASONS FOR PERFORMING STUDY: The proposed biological mechanisms for exercise-induced pulmonary haemorrhage (EIPH) are many and varied. Better knowledge of risk factors should lead to achievable measures to reduce the incidence. OBJECTIVES: To identify risk factors associated with epistaxis following racing in UK Thoroughbreds, to gain possible insights into the pathogenesis of the condition and to investigate the association between epistaxis and race finishing position. METHODS: The association of epistaxis occurring on UK racecourses between 1996 and 1998 with a wide range of race-, horse- and start-level variables was examined in multivariable mixed effect logistic regression analyses. Four multivariable analyses were conducted, one for all race types considered collectively and one each for flat, hurdle and steeplechase race types considered separately. RESULTS: Risk of epistaxis was significantly increased for hurdle and steeplechase race types compared to both flat and National Hunt flat races. In 3 of the 4 final models, there was a significant biological trend for increasing risk of epistaxis with increasing ground hardness ('going') and accumulated years spent racing. However, in flat races epistaxis was such a rare outcome (0.33 cases per 1000 starts) that this subset analysis had insufficient power to measure the detectable effect of 'going' as statistically significant. Horses with epistaxis were significantly more likely to have a poorer finishing position than those without blood at the nostrils. CONCLUSIONS: Findings were consistent with the theory that locomotory impact-induced trauma contributes to exercise-induced epistaxis. Further validation of this hypothesis through application of similar methods to endoscopically visible EIPH and through biomechanical studies is warranted. POTENTIAL RELEVANCE: Knowledge of significant risk factors should allow formulation of practical measures, such as track watering, to reduce the risks of EIPH and epistaxis in racehorses.

Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone.

REASONS FOR PERFORMING STUDY: Inhaled ozone can induce oxidative injury and airway inflammation. Horses affected by recurrent airway obstruction (RAO) have a decreased pulmonary antioxidant capacity, which may render them more susceptible to oxidative challenge. It is currently unknown whether RAO-affected horses are more susceptible to oxidative stress than those unaffected by RAO. OBJECTIVES: To determine whether ozone exposure induces greater oxidative stress and airway inflammation in RAO-affected horses in remission than in healthy horses. METHODS: Seven healthy control horses and 7 RAO-affected horses were exposed to 0.8 ppm ozone for 2 h at rest. RESULTS: At baseline, bronchoalveolar lavage fluid (BALF) ascorbic acid concentrations were lower in RAO-affected horses than healthy controls. Ozone appeared to preferentially oxidise glutathione rather than ascorbic acid 6 h after exposure. Individual healthy and RAO-affected horses demonstrated oxidation of BALF glutathione after ozone exposure. Overall, RAO-affected horses did not demonstrate increased oxidative stress following ozone exposure, compared with healthy horses. Ozone did not induce significant airway inflammation in either group. CONCLUSIONS: RAO-affected horses in remission are not more sensitive to ozone despite a decreased pulmonary antioxidant capacity. Sensitivity to ozone appears to be independent of initial pulmonary antioxidant status. POTENTIAL RELEVANCE: Horses with high susceptibility to oxidative stress may benefit from antioxidant supplementation.

Effects of nitric oxide inhibition on thermoregulation during exercise in the horse.

We investigated the role of NO in the control of thermoregulation. We measured sweating rate and body temperatures (core, rectal and skin) in five thoroughbred horses during exercise of variable intensity on a high-speed treadmill. A standard exercise test (SET) consisting of three canters (8 m s-1), with walking and trotting between each canter, was performed twice, in random order, by each horse and N omega-nitro-L-arginine methyl ester (L-NAME; 20 mg ml-1), a competitive inhibitor of nitric oxide synthase (NOS), was infused into the central circulation after the first canter in the test SET only. L-Arginine (200 mg ml-1), a substrate of NOS, was injected after the second canter in both control and test SETs. L-NAME significantly (p < 0.05) reduced the sweating rate measured on the neck (31.6 +/- 6.4 versus 9.7 +/- 4.2 g/min/m2) and rump (14.7 +/- 5.2 versus 4.8 +/- 1.6 g/min/m2) while raising the core temperature (39.7 +/- 0.2 versus 40.6 +/- 0.7 degrees C, p < 0.05) during the second canter. In the third canter, sweating rate had increased after giving L-arginine during the test SET, but had not returned to levels measured at similar times during the control SET. Core, rectal and skin temperatures continued to rise and were significantly higher than control levels, despite giving L-arginine. The results show that inhibition of NO production reduces sweating rate in the horse during exercise thereby inducing a rise in body temperatures.

Metabolic response to maximal exercise of 800 and 2,000 m in the thoroughbred horse.

To define the metabolic response to maximal exercise in the thoroughbred horse under field conditions, muscle biopsies and venous blood samples were taken from five horses after a single 800-m gallop and from four horses after a single 2,000-m gallop. Muscle and blood samples were also collected during 60 min of recovery. After exercise muscle ATP contents were decreased by 30 +/- 7 (SD) and 47 +/- 3% after the 800- and 2,000-m gallops, respectively. As indicators of purine catabolism, ammonia and uric acid increased in plasma, the accumulation being greater after the 2,000-m gallop. Blood ammonia peaked immediately after exercise and uric acid after 40-60 min of recovery. Muscle glycogen utilization over the 800- and 2,000-m gallops averaged 2.68 +/- 0.90 and 1.06 +/- 0.12 mmol glucosyl units.kg dry muscle-1.s-1, respectively, and the total used amounted to 27.3 +/- 6.6 and 32.5 +/- 8.8% of the initial store. Muscle lactate accumulation averaged 123.5 +/- 49.7 and 167.3 +/- 20.7 mmol/kg dry muscle, respectively, and declined during recovery with half times of 22.9 +/- 4.2 and 18.9 +/- 6.6 min. Blood lactate peaked 5-10 min after exercise. Exercise resulted in only a small increase in muscle glycerol content, but this continued to rise during recovery reaching 9-12 mmol/kg dry muscle after 20 min. During this time the increase in muscle glycerol content exactly matched the decline in glycerol 3-phosphate.

Nitric oxide and thermoregulation during exercise in the horse.

The effect of inhibition of nitric oxide production on sweating rate (SR) and on core, rectal, and tail skin temperatures was measured in five Thoroughbred horses during exercise of variable intensity on a high-speed treadmill. A standard exercise test consisting of three canters [approximately 55% maximum O2 uptake (VO2max)], with walking (approximately 9% VO2max) and trotting (approximately 22% VO2max) between each canter, was performed twice (control or test), in random order, by each horse. N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg), a competitive inhibitor of nitric oxide synthase, was infused into the central circulation and induced a significant reduction in the SR measured on the neck (31.6 +/- 6.4 vs. 9.7 +/- 4.2 g x min(1) x m(-2); 69%) and rump (14.7 +/- 5.2 vs. 4.8 +/- 1.6 g x min(-1) x m(-2); 67%) of the horses during canter (P < 0.05). Significant increases in core, rectal, and tail skin temperatures were also measured (P < 0.05). L-Arginine (200 mg/kg iv) partially reversed the inhibitory effects of L-NAME on SR, but core, rectal, and tail skin temperatures continued to increase (P < 0.05), suggesting a cumulation of body heat. The results support the contention that nitric oxide synthase inhibition diminishes SR, resulting in elevated core and peripheral temperatures leading to deranged thermoregulation during exercise. The inhibition of sweating by L-NAME may be related to peripheral vasoconstriction but may also involve the neurogenic control of sweating.

NO inhalation reduces pulmonary arterial pressure but not hemorrhage in maximally exercising horses.

In horses, the exercise-induced elevation of pulmonary arterial pressure (Ppa) is thought to play a deterministic role in exercise-induced pulmonary hemorrhage (EIPH), and thus treatment designed to lower Ppa might reasonably be expected to reduce EIPH. Five Thoroughbred horses were run on a treadmill to volitional fatigue (incremental step test) under nitric oxide (NO; inhaled 80 ppm) and control (N(2), same flow rate as per NO run) conditions (2 wk between trials; order randomized) to test the hypothesis that NO inhalation would reduce maximal Ppa but that this reduction may not necessarily reduce EIPH. Before each investigation, a microtipped pressure transducer was placed in the pulmonary artery 8 cm past the pulmonic valve to monitor Ppa. EIPH severity was assessed via bronchoalveolar lavage (BAL) 30 min postrun. Exercise time did not differ between the two trials (P > 0.05). NO administration resulted in a small but consistent and significant reduction in peak Ppa (N(2), 102.3 +/- 4.4; NO, 98.6 +/- 4.3 mmHg, P < 0.05). In the face of lowered Ppa, EIPH severity was significantly higher in the NO trial (N(2), 22.4 +/- 6.8; NO, 42.6 +/- 15.4 x 10(6) red blood cells/ml BAL fluid, P < 0.05). These findings support the notion that extremely high Ppa may reflect, in part, an arteriolar vasoconstriction that serves to protect the capillary bed from the extraordinarily high Ppa evoked during maximal exercise in the Thoroughbred horse. Furthermore, these data suggest that exogenous NO treatment during exercise in horses may not only be poor prophylaxis but may actually exacerbate the severity of EIPH.

Validation of a cardiac monitor for measuring heart rate variability in adult female pigs: accuracy, artefacts and editing.

Autonomic regulation of cardiac activity during stress has not been clearly defined in farm animals. In part, this is due to the limited availability of affordable ambulatory cardiac monitors capable of accurately monitoring and storing large amounts of data that meet the criteria necessary for heart rate variability analysis. Our objectives were to measure the accuracy of a 24-h Polar RR monitor using gold standard ECG, to examine and categorise any occurring anomalies and to ascertain their impact on the outcome of heart rate variability analysis. Five 1-year-old female pigs (gilts) were socially isolated from their pen mates and cardiac activity was simultaneously measured using two systems, a 24-h Polar RR Recorder and a Telemetric ECG system. The Polar data were manually assessed both against and in isolation of the ECG data to identify anomalous beats, which were then assigned to one of five identified error categories. The anomalies in the Polar data were corrected and statistical comparisons were performed among the three data sets to evaluate the effects of anomalies on heart rate variability analysis. Bland-Altman analysis was used to measure the level of agreement among the ECG, Uncorrected Polar and Corrected Polar data. No anomalies or ectopies were found in the ECG data but 46 anomalies (0.81% of total interbeat intervals [IBI]) were found in the Polar Uncorrected data. Manual identification and editing procedures reduced this error to 0.018%. Most mean heart rate and IBI parameters were unaffected by error (P>.05). Standard deviation (S.D.) and root mean square of successive differences (RMSSD) were 45% and 50% higher when anomalies were present in the data. Artefacts affected the magnitude of the frequency domain indices and overestimated total and parasympathetic activity and underestimated sympathetic activity. The mean difference between ECG and Uncorrected Polar data was 1.36 ms (limits of agreement -69.03 to 71.74 ms). This was greatly improved to 0.36 ms (limits of agreement -5.37 to 6.10 ms) after editing. Overall, even a small proportion of error biased the outcome of heart rate variability analysis. This bias was greatly reduced by correcting the anomalous beats. Bland-Altman analysis demonstrated that when there was error present in the Polar data, it could not be used interchangeably with the ECG data. However, if there were no anomalies present in the data or if they were classified and corrected using the approach in this study, then the two systems could be used interchangeably.

Comparison of the performance of linear resistance and ultrasonic pneumotachometers at rest and during lobeline-induced hyperpnoea.

The performance of a Fleisch No. 5 pneumotachometer (F), and two commercial ultrasonic pneumotachometers, the BRDL (B) and the Spiroson (S) systems were compared in respect to their use for determination of ventilatory parameters at rest and during lobeline-induced hyperpnoea. Five clinically healthy Thoroughbred horses were tested with the three pneumotachometers in random order. Respiratory airflow, respired gas concentrations, oesophageal pressures, pressures within the mask systems and arterial blood gases were determined before and during lobeline-induced hyperpnoea. Because measured peak expiratory airflow rates exceeded the stated linear range of the Fleisch pneumotachometer ( approximately +/- 25 l s(-1)) differential pressure-flow curves were determined in vitro over the range of flows recorded in vivo. Expired flows greater than the linear range were corrected according to the derived regression equation. No differences in any of the measured variables among the three systems were present at rest. At peak ventilation of lobeline-induced hyperpnoea mask pressures [Delta P(mask)(mean (SEM)): F: 9.6 (2.8) cm H(2)O, B: 0.8 (0.4) cm H(2)O, S: 1.4 (0.8) cm H(2)O] and end tidal carbon dioxide [ ET CO(2)(mean (SEM)): F: 2. 6 (0.1)%, B: 2.1 (0.2)%, S: 2.1 (0.1)%] were significantly higher in system F. Despite a tendency for respiratory frequency and peak inspired and expired flows, to be lower with system F, no significant differences in the measurements of ventilatory mechanics were detected. In conclusion, the ultrasonic flowmeters pose significantly lower resistive loads onto the respiratory system during ventilation above resting levels than Fleisch No 5 pneumotachometers. However, at the flowrates achieved during lobeline-induced hyperpnoea an in vitro calibration of the differential pressure-flow relationship allows correction for expiratory alinearity in system F. In addition, the performance of the Spiroson flowmeter is accurate in determining ventilatory mechanics at rest and during lobeline-induced hyperpnoea.

Metabolic effects of nitric oxide synthase inhibition during exercise in the horse.

The effect of nitric oxide synthase (NOS) inhibition during exercise on lactate production was investigated in five Thoroughbred horses. A standard exercise test (SET), consisting of three canters (approximately 55 per cent VO2max), with walking and trotting between each canter, was performed twice (control and test, in random order) by each horse. Nphi-nitro-L-arginine methyl ester (L-NAME; 20 mg kg-1), a competitive inhibitor of NOS, induced a significant increase (P < 0.05) in plasma lactate [5.7 (2.9) vs 11.8 (3.8) mmol L-1], which continued to increase despite administration of L-arginine, the substrate for NOS. There were no differences in cardiac output (Q) or the total body oxygen consumption (VO) between each SET. The results show that non-specific inhibition of NOS isoforms during exercise in the horse increases plasma lactate concentration, although the mechanism/s remain uncertain.

Cardiovascular demands of competition on low-goal (non-elite) polo ponies.

Knowledge of the competitive demands of different sports or activities is important for designing appropriate training programmes to ensure that animals reach a sufficient level of fitness to reduce the risk of overexertion and injury or illness and to achieve the best possible performance in relation to an individual's genetic potential. Whilst the physiological demands of many equestrian sports have been described, to the best of our knowledge the cardiovascular demands of polo have not. The aims of the present study were therefore to record heart rate during and after competitive polo games in a group of low-goal (non-elite) polo ponies in order to describe the absolute heart rates during play, the relationship of these heart rates to maximal heart rate and the characteristics of a typical chukka in terms of effort. Six low-goal polo ponies were studied during a total of 59 chukkas. Heart rate was monitored continuously before, during and after competition using a commercial heart rate monitor. Maximal heart rate was determined with field and treadmill incremental exercise tests and used to express work intensity in terms of time during play that each ponies heart rate was less than 75% HRmax, between 75 and 90% HRmax and greater than 90% HRmax. Mean maximum heart rate was not different during play or during field and treadmill exercise tests; 215+/-7 (mean +/- s.d.), 211+/-7 and 213+/-2 beats/min, respectively (P>0.05). Mean heart rate for all ponies over all chukkas was 166+/-6 beats/min with a mean chukka duration of 611+/-18 s. Of this time, 44+/-7% of the time was spent below 75% HRmax, 39+/-8% between 75 and 90% HRmax and 17+/-8% of time above 90% HRmax. When only one chukka had been played, there was a good correlation between mean heart rate during play and 3 min recovery heart rate (r = 0.63, P<0.001). Based on these observations, it is proposed that low-goal polo places moderate to high stress on the cardiovascular system.

Titrimetric determination of muscle buffering capacity (beta mtitr) in biopsy samples.

In vitro titration of muscle homogenates has been used to assess muscle buffering capacity (beta mtitr) in a variety of species. In the present study, factors likely to affect the estimation of beta mtitr were investigated. Also, values of beta mtitr from normal Thoroughbred horses are presented. A non-linear titration curve was obtained with addition of HCl to muscle homogenates. As a result, beta mtitr is expressed as the mumol H+ required to change the pH of 1g of dry muscle or wet muscle from 7.1 to 6.5. An effect of dilution on the initial pH was found below 40 mg wet muscle per ml homogenising reagent (10 mg dry muscle per ml) and on beta mtitr below 10 mg wet muscle. As a result, 40 mg wet muscle or 10 mg dry muscle per ml was chosen as the minimum concentration for determination of beta mtitr. Incubation of homogenates up to 60 mins did not affect beta mtitr significantly. As a mean, beta mtitr in wet muscle was approximately 25 per cent higher compared to dry muscle. The beta mtitr of dry muscle was increased by approximately 18 per cent when HCO3- was added in an amount equivalent to the calculated HCO3- content of wet muscle at rest. The homogenisation process resulted in complete loss of adenosine triphosphate and phosphocreatine with only small changes in adenosine diphosphate and adenosine monophosphate. It was concluded that the estimates of beta mtitr did not include any contribution from 'dynamic' buffering via rephosphorylation of adenosine diphosphate by phosphocreatine, and in dry muscle it was accounted for mainly through physico-chemical buffering by phosphates, proteins and dipeptides. beta mtitr determined in biopsy samples of muscle from 20 Thoroughbred horses ranged from 100.8 to 131.8 mumol H+/g dry muscle pH 7.1 to 6.5 (mean 121.2, sd +/- 7.4).

Equine pulmonary and systemic haemodynamic responses to endothelin-1 and a selective ET(A) receptor antagonist.

Based on previous in vitro studies, we hypothesised that endothelin (ET) would induce vasoconstriction in the pulmonary circululation of the horse and that this action would be mediated via ET(A) receptors. Pulmonary and systemic haemodynamic responses to endothelin-1 (ET-1), a potent vasoactive endogenous peptide, were investigated in 6 conscious, nonsedated horses at rest. Bolus i.v. injections of exogenous ET-1 (0.1, 0.2 and 0.4 microg/kg bwt) caused significant increases in pulmonary (PAP) and carotid (CAP) artery pressures, with peak increases of 79% and 51% for mean PAP and CAP, respectively. The effect of ET-1 on PAP and CAP was rapid and transient for PAP (-10 min) but prolonged for CAP (up to 60 min). ET-1 significantly decreased cardiac output by up to 35% and significantly increased systemic vascular resistance (SVR) by up to 104%. Pulmonary vascular resistance (PVR) showed a trend (P>0.05) to increase with 0.2 and 0.4 microg/kg bwt ET-1. Infusion of a selective ET(A) receptor antagonist (TBC11251) completely inhibited the responses to a subsequent bolus of 0.2 microg/kg bwt ET-1. We conclude that exogenous ET-1 exerts a potent vasoconstrictive action on the pulmonary and systemic circulations of the horse. These effects appear to be mediated largely through ET(A) receptors in both circulations. Endothelin may play a role in hypertensive conditions in the horse.

Endothelin in the equine hypoxic pulmonary vasoconstrictive response to acute hypoxia.

Elevated concentrations of endothelin (ET), a potent endothelium-derived vasoactive peptide, have been reported in a number of pathophysiological conditions associated with pulmonary hypertension, both in the horse and other species. We have previously shown, both in vitro and in vivo, that the pulmonary and systemic vascular response to exogenous ET is mediated predominantly via ET(A) receptors. Our hypothesis in the present study was that ET is involved in the equine hypoxic pulmonary vasoconstrictive response to acute hypoxia. In this study, we investigated the effects of a selective ET(A) receptor antagonist on hypoxic pulmonary hypertension in the mature horse. Horses were exposed to a 10 min period of hypoxia (F(I)O2 approximately 0.11) on 2 occasions, with and without pretreatment with the selective ET(A) receptor antagonist TBC11251 (10 mg/kg bwt i.v.). Hypoxia increased mean pulmonary artery pressure (PAP) from 18.3+/-0.9 (mean +/- s.e. normoxia) to 28.0+/-0.8 mmHg (hypoxia) in the session without ET(A) receptor antagonism. Carotid arterial pressure (CAP) also increased progressively throughout the period of hypoxic challenge and at the end was 153+/-5 mmHg (hypoxia) compared to during normoxia (140+/-5 mmHg). There was no significant overall effect of ET(A) receptor antagonism on the haemodynamic or ventilatory responses to acute hypoxia. However, between 5 and 10 min of hypoxia there was a trend for the mean PAP to diverge in the 2 treatments, which just failed to reach significance at 10 min of hypoxia (P = 0.053). In conclusion, this study describes the haemodynamic and ventilatory changes in response to a period of acute hypoxia in the adult horse. The results do not support a role for ET as a mediator of acute HPV in the horse, but suggest that it may be involved as a modulator or in the slower (>10 min) phase of HPV.

Plasma aspartate aminotransferase and creatine kinase activities in thoroughbred racehorses in relation to age, sex, exercise and training.

In order to investigate the effect of age, sex and month on the response of plasma aspartate aminotransferase (AST) and creatine kinase (CK) to exercise, blood samples were collected once a month between March and September from a group of 40 2- and 3-year-old (2yo and 3yo) thoroughbred racehorses (kept under the same managemental regimen) at rest before exercise (PRE) and at 2 (2H) and 24 h (24H) post-exercise. The absolute change in activities between the 2H and PRE samples (2H delta) and the 24H and PRE samples (24H delta) was also calculated. Age had a significant effect on all measured and calculated parameters for colts (C), apart from 24H delta CK but showed no effect in the fillies (F). Sex only had a significant effect in the 3yo in the 2H delta CK. In the 2yo, significant effects of sex were found for both CK and AST in the PRE, 2H and 24H samples. The effect of month varied according to the classification group with only the 2yoC not showing any significant effect on any parameter. Fillies were, in general, more likely than colts to show greater than a twofold increase in CK activity at 2H post-exercise and the number of animals showing such an increase decreased as the season progressed. Very little change in AST activities occurred with exercise.

Exercise-induced pulmonary haemorrhage (EIPH) in horses results from locomotory impact induced trauma--a novel, unifying concept.

Exercise-induced pulmonary haemorrhage (EIPH) in horses, although of major welfare and economic importance worldwide, is of uncertain cause. It is accepted that the dorsocaudal region of the lung is particularly prone to the condition, but present theories of causation cannot satisfactorily explain the mechanism or pattern of occurrence. We propose that EIPH results from locomotory impact induced trauma; the mechanism being similar to that producing lung tissue damage following thoracic impact injury. In impact injury, the localised impulsive load on the chest wall is transmitted by pressure waves through the lung at a slower speed than in the chest wall. The waves are subsequently reflected from the distal chest wall and other structures, producing a complex pattern of wave motion; waves travelling from regions of large cross-section to narrower ones are amplified in magnitude, consequently these regions can experience very high local stresses. Compression/dilation and shear waves are produced within the parenchyma and the latter particularly have been implicated as the cause of parenchymal damage and rupture with oedema and haemorrhage. This form of soft tissue damage has been shown to occur at remarkably low loads with an impact velocity greater than about 11 m/s and pressure exceeding approximately 14 kPa. In the horse, the lung is subjected to comparable levels of locomotory derived impulsive force during moderate to high speed exercise and this is the basis of the mechanism causing EIPH. During locomotion, the force following ground-strike of the front legs is transmitted, with some attenuation, through the forelimbs to the scapulae. The anatomical arrangement of the scapula, coupled with the direction of the force at the shoulder (scapulo humeral joint) produces an impulsive force on the rib cage, approximately just below mid height of the frontal aspect of the chest approximately over the fourth rib. As a result, pressure waves are transmitted through the lung parenchyma towards the dorsal and caudal regions; these waves are subsequently reflected at the distal chest wall, spine and diaphragm causing a complex pattern of wave interaction. The observed locations of EIPH are at the sites where wave intensity is expected to be greatest due to changes in cross section and reflection. Based on available information, it is estimated that impulsive forces of more than 100 kPa, lasting approximately 10 ms, would be applied to the chest wall by each scapula in a 500 kg horse when galloping; this level of force would be sufficient to cause oedema and haemorrhage as observed in impact induced injury.

Quantification of the response of equine apocrine sweat glands to beta2-adrenergic stimulation.

The aim of the present study was to characterise the quantitative sweating response of the horse to beta2-adrenergic stimulation. The sweating responses of 6 horses to the randomised infusion of 8 different adrenaline concentrations (0.025, 0.05, 0.075, 0.1, 0.2, 0.4, 1.0 or 2.0 microg/kg bwt/min), was investigated. Sweating rate (SR) and skin temperature (TSK) on the neck (N) and gluteal region (G), and plasma adrenaline and noradrenaline concentrations were measured. Peak SR was approximately 15 (N) and approximately 9 g/m2/min (G) during infusion of both 1.0 and 2.0 microg/kg bwt/min adrenaline. Sweat produced per nmol/l plasma adrenaline peaked during the infusion of 0.075 microg/kg bwt/min adrenaline. Higher adrenaline infusion concentrations resulted in a progressive decrease in the amount of sweat produced per nmol/l plasma adrenaline and a plateau of 6 g/m2/(nmol/l) plasma adrenaline was reached for infusions between 1.0 and 2.0 microg/kg bwt/min. Peak SR were far lower than we have previously reported during exercise. There was no evidence of sweat gland fatigue or vasoconstriction during infusion, suggesting saturation of sweat gland beta2 receptors. We conclude that sweating in the horse is under dual control from a combination of hormonal and neural mechanisms.