Interobserver Variation in the Diagnosis of Neurologic Abnormalities in the Horse.

BACKGROUND: The diagnosis of equine protozoal myeloencephalitis (EPM) relies heavily on the clinical examination. The accurate identification of neurologic signs during a clinical examination is critical to the interpretation of laboratory results. OBJECTIVE: To investigate the level of agreement between board-certified veterinary internists when performing neurologic examinations in horses. ANIMALS: Ninety-seven horses admitted to the Veterinary Teaching Hospital at The Ohio State University from December 1997 to June 1998. METHODS: A prospective epidemiologic research design was used. Horses enrolled in the study were examined by the internist responsible for care of the horse, and later by an internist who was not aware of the presenting complaint or other patient history. Data were analyzed by descriptive statistics, and kappa (K) statistics were calculated to assess interobserver agreement. RESULTS: Ninety-seven horses were enrolled in the study. Overall, examiners, also referred to as observers, agreed that 60/97 (61.9%) were clinically abnormal, 21/97 (21.6%) were clinically normal, and the status of 16/97 (16.5%) of horses was contested. There was complete agreement among the examiners with regard to cranial nerve signs and involuntary movements. Disagreement involving severity of clinical signs occurred in 31 horses, and 25 of those horses (80.6%) were considered either normal or mildly affected by the primary observer. When examining the results of all paired clinical examinations for 11 different categories, there was wide variability in the results. When examiners rated the presence or absence of any neurologic abnormalities, lameness, or ataxia, the agreement among observers was either good or excellent for 80% of horses. When assessing truncal sway, the agreement among observers was good or excellent for 60% of the horses. When examining the horses for asymmetry of deficits, agreement was either good or excellent for 40% of the horses. Agreement among observers was excellent or good for only 20% of the horses when assessing muscle atrophy, spasticity (hypermetria), and overall assessment of the severity of neurologic abnormalities. CONCLUSIONS AND CLINICAL IMPORTANCE: This study underscores the subjectivity of the neurologic examination and demonstrates a reasonable level of agreement that may be achieved when different clinicians examine the same horse.

Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia.

Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required.

Exercise induced pulmonary hemorrhage in horses: American College of Veterinary Internal Medicine consensus statement.

BACKGROUND: Published studies of exercise-induced pulmonary hemorrhage (EIPH), when assessed individually, often provide equivocal or conflicting results. Systematic reviews aggregate evidence from individual studies to provide a global assessment of the quality of evidence and to inform recommendations. OBJECTIVES: Evaluate evidence to determine: if EIPH adversely affects the health, welfare or both of horses; if EIPH affects the athletic capacity of horses; the efficacy of prophylactic interventions for EIPH; and if furosemide affects the athletic capacity of horses. ANIMALS: None. MATERIALS AND METHODS: Systematic review. A panel of 7 experts was formed to assess evidence in the peer reviewed literature addressing each of the 4 objectives. Methodology followed that of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Publications were assessed for quality of evidence by working groups of the panel, and a summary of findings was presented in tables. Recommendations were based on quality of evidence and were determined by a vote of the panel. RESULTS: Much of the evidence was of low to very low quality. Experimental studies frequently lacked adequate statistical power. There was moderate to high quality evidence that EIPH is progressive, is associated with lung lesions, that it adversely affects racing performance, that severe EIPH (Grade 4) is associated with a shorter career duration, that furosemide is efficacious in decreasing the incidence and severity of EIPH, and that administration of furosemide is associated with superior race performance. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Strong recommendation that EIPH be considered a disease and a weak recommendation for use of furosemide in management of racehorses with EIPH.

A systematic review and meta-analysis of the efficacy of furosemide for exercise-induced pulmonary haemorrhage in Thoroughbred and Standardbred racehorses.

REASONS FOR PERFORMING STUDY: Furosemide is the most commonly used medication for exercise-induced pulmonary haemorrhage (EIPH); however, critical evaluation of the strength of evidence for efficacy of furosemide is lacking and is warranted so that evidence-based treatment decisions can be made. OBJECTIVES: To evaluate the efficacy of furosemide to reduce the severity or frequency of detection of EIPH in Thoroughbred and Standardbred racehorses. STUDY DESIGN: Systematic review with meta-analyses. METHODS: Primary studies were identified via searches of electronic databases, relevant texts and reference lists of published articles. Studies were not restricted by date or publication status. Only studies published in English were eligible for inclusion. Searches were performed using a predetermined search string. Randomised controlled trials, nonrandomised trials and observational studies were included. Three authors independently assessed each study using the Cochrane collaboration guidelines and Grading of Recommendations Assessment, Development and Evaluation recommendations for rating quality of evidence. Meta-analysis of studies was performed with pooled data to determine whether furosemide reduced the frequency of detection of EIPH (yes or no) as evaluated by tracheobronchoscopy or bronchoalveolar lavage fluid red blood cell number, or if furosemide reduced the severity of EIPH by at least one tracheobronchoscopic grade. RESULTS: Seventeen studies fulfilled the inclusion criteria. The relative risk of detecting any EIPH by tracheobronchoscopy after administration of furosemide was 0.88 (pooled data from 11 studies, n = 5780; 95% confidence interval 0.79-0.97, P = 0.01). When data from only high-quality randomised controlled trials (2 studies, n = 405) were used, the relative risk of detecting endoscopically evident EIPH was 0.68 (95% confidence interval 0.58-0.79, P<0.001). The proportion of horses previously diagnosed with EIPH having a reduction of at least one EIPH grade after furosemide was 68% (2 studies, n = 405; 95% confidence interval 61-78%). CONCLUSIONS: There is high-quality evidence, albeit limited, that administration of furosemide reduces the incidence and severity of EIPH in Thoroughbred or Standardbred racehorses.

Exercise-induced pulmonary haemorrhage impairs racing performance in Thoroughbred racehorses.

REASONS FOR PERFORMING STUDY: Exercise-induced pulmonary haemorrhage (EIPH) occurs commonly in Thoroughbred racehorses worldwide. While EIPH is believed to be an important cause of impaired performance in these horses, there is limited evidence from sufficiently powered studies to evaluate this association. OBJECTIVES: To evaluate whether EIPH is associated with finishing position, distance finished behind race winners and differences in race earning among Thoroughbred horses racing in South Africa. STUDY DESIGN: Prospective cross-sectional study. METHODS: One thousand Thoroughbred horses racing in South Africa were enrolled prior to a single race and underwent tracheobronchoscopic examination within 2 h of racing. Three observers, blinded to the horses' identity and race performance, independently evaluated EIPH occurrence and severity using video recordings of the examination. Data were analysed using multivariable logistic and linear regression while controlling for important horse and race factors as potential confounding variables. RESULTS: Overall, 68% of horses had evidence of EIPH (grade ≥1). Horses without evidence of EIPH (severity grade 0), when compared with horses with any evidence of EIPH (grade ≥1), were >2 times more likely to win races (odds ratio = 2.3; 95% confidence interval 1.4-3.7; P = 0.001), finished an average of one length ahead of horses with EIPH (P = 0.03), and were 2.5 times more likely to be in the highest decile in race earnings (odds ratio = 2.5, 95% CI 1.5-4.1, P<0.001). However, no association was identified regarding finishing in the top 3 positions or earning money when analysed as a continuous variable or analysed as any winnings vs. none. CONCLUSIONS: Exercise-induced pulmonary haemorrhage was associated with impaired performance in Thoroughbred racehorses not medicated with furosemide and not using nasal dilator strips. These findings provide strong corroboration of previous research indicating that the occurrence of EIPH has a major impact on the ability of Thoroughbred racehorses to compete successfully as elite athletes.

Prospective study of the association between exercise-induced pulmonary haemorrhage and long-term performance in Thoroughbred racehorses.

REASONS FOR PERFORMING STUDY: Exercise-induced pulmonary haemorrhage (EIPH) is associated with impaired short-term race performance but consequences to long-term race performance of Thoroughbred racehorses are unknown. Knowledge of effects of EIPH on performance over a prolonged time would inform the need for management and treatment of this disorder. OBJECTIVES: To determine the relationship between EIPH detected on a single occasion and long-term athletic performance in Thoroughbred racehorses. STUDY DESIGN: Prospective, longitudinal, observational epidemiological study conducted from 2003 to 2012. METHODS: Seven hundred and forty-four Thoroughbred racehorses underwent a single tracheobronchoscopic examination to determine presence and severity of EIPH in 2003. Following retirement of all the horses from racing, career after examination and lifetime performance data (including career duration, earnings, starts, wins and placings) were abstracted from a commercial database. The association between presence and severity of EIPH and individual performance variables were analysed using survival analysis, linear regression and negative binomial regression. RESULTS: No association was detected between the presence of any EIPH (grade ≥1) and all measures of long-term performance examined except that horses with EIPH (grade ≥2) had fewer earnings after endoscopic examination than did horses with mild EIPH or no EIPH (grades ≤1). Multiple associations were detected between the most severe form of EIPH (grade 4) and measures of long-term performance suggesting that the severity of EIPH commonly associated with epistaxis adversely affects either the horse's opportunity to race or physiologic capacity to race. CONCLUSIONS: We conclude that there is no association between EIPH grades 0, 1, 2 and 3 and long-term racing performance of Thoroughbred racehorses. These results are based on a single endoscopic evaluation of EIPH grade made during a horse's career. Further studies are required to determine the reasons for an association of severe (grade 4) EIPH with impaired long-term race performance.

Effect of body position on electrocardiographic recordings in dogs.

OBJECTIVE: To determine whether body position (standing vs right lateral recumbency) altered the quality of the electrocardiogram (ECG) and value of ECG variables in dogs when the ECG was recorded using American Heart Association guidelines for frequency response. DESIGN: Crossover study using a convenience sample. METHODS: ECGs were recorded twice in 65 sled dogs in random order with each dog standing or placed in right lateral recumbency. Lead II and three semi-orthogonal leads (I, aVF, and V10 ) were recorded and muscle tremor artefact was assessed. RESULTS: Lead II ECGs obtained from dogs in right lateral recumbency had less muscle tremor artefact and consequently a shorter QRS duration than ECGs obtained with the dogs standing. The P, Q, R and S wave amplitudes differed in selected leads and the mean electrical axis was shifted 20° to the right when dogs were in right lateral recumbency. CONCLUSIONS: Right lateral recumbency improves the quality of ECG recording in dogs by decreasing muscle tremor artefact, alters the amplitude of P, R and S waves in specific leads and results in a rightward shift in the mean electrical axis, relative to standing.

Serum cardiac troponin I concentrations in horses with cardiac disease.

OBJECTIVES: To measure the cardiac troponin I (cTnI) concentration in horses and determine whether it could be used in the diagnosis of myocardial disease, as well as determining the association between cTnI and survival. DESIGN: Prospective, observational study. PROCEDURE: Physical examination, echocardiography, telemetric electrocardiography and postmortem were used to diagnose cardiac disease. Diagnoses were grouped as myocardial disease, structural heart disease or lone arrhythmia. Blood samples were collected at admission for cTnI analysis and the results were compared with those for 18 healthy horses. RESULTS: In total, 49 horses were admitted with cardiac disease. Elevated cTnI concentration (>0.03 ng/mL) was observed in a greater proportion of horses with myocardial disease (7/7), compared with healthy horses (0/18; P < 0.0001), horses with structural heart disease (7/25; P = 0.001), and horses with a lone arrhythmia (2/17; P = 0.0001). The median cTnI concentration for horses with myocardial disease was 17.5 ng/mL (range 0.78-49.87 ng/mL), which was higher than in the healthy horses (0.01 ng/mL, range 0.01-0.03 ng/mL; P < 0.0001). Of the 49 horses with cardiac disease, the median cTnI concentration for non-survivors (0.28 ng/mL, range 0.01-49.87 ng/mL) was higher than for survivors (0.01 ng/mL, range 0.01-30.31 ng/mL; P = 0.0035). However, the proportion of surviving horses with an elevated cTnI (10/39, 26%) was not significantly different from the proportion of non-surviving horses with an elevated cTnI (6/10, 60%; P = 0.060). CONCLUSIONS: cTnI is elevated in horses with myocardial disease and elevated to a lesser degree in some horses with structural heart disease or lone arrhythmias. The association between cTnI concentration and survival was not clear.

Risk factors for exercise-induced pulmonary haemorrhage in Thoroughbred racehorses.

REASONS FOR PERFORMING STUDY: Risk factors for occult exercise-induced pulmonary haemorrhage (EIPH) are poorly defined or quantified. OBJECTIVES: To investigate the importance of putative risk factors for EIPH amongst Thoroughbred racehorses in Australia. METHODS: Tracheobronchoscopy was used to determine EIPH status of 744 Thoroughbred racehorses after flat racing in Melbourne, Australia. Horses were identified for study before racing, and over 50% of horses racing during the study period were examined. Statistical analysis included use of bivariate and multivariate logistic regression analysis to account for simultaneous effects of a large number of variables. RESULTS: The only risk factor identified as associated with both EIPH ≥ 1 or ≥ 2 was ambient temperature, with horses racing at temperatures <20 °C being at ∼ 2 times risk of occult EIPH. There was no association of EIPH with age, sex, weight carried, track hardness, speed of racing, or air quality. CONCLUSIONS: There do not appear to be individual risk factors, amongst those examined in this study, that are strongly associated with EIPH. POTENTIAL RELEVANCE: The risk of developing EIPH cannot be readily determined from a combination of age, race speed, race distance, track hardness or air quality. This study does not provide support for the hypotheses that racing on hard surfaces or in polluted air contributes to the development of EIPH.

Proinflammatory cytokine and chemokine gene expression profiles in subcutaneous and visceral adipose tissue depots of insulin-resistant and insulin-sensitive light breed horses.

BACKGROUND: Insulin resistance has been associated with risk of laminitis in horses. Genes coding for proinflammatory cytokines and chemokines are expressed more in visceral adipose tissue than in subcutaneous adipose tissue of insulin-resistant (IR) humans and rodents. HYPOTHESIS/OBJECTIVES: To investigate adipose depot-specific cytokine and chemokine gene expression in horses and its relationship to insulin sensitivity (SI). ANIMALS: Eleven light breed mares. METHODS: Animals were classified as IR (SI=0.58+/-0.31x10(-4) L/min/mU; n=5) or insulin sensitive (IS; SI=2.59+/-1.21x10(-4) L/min/mU; n=6) based on results of a frequently sampled intravenous glucose tolerance test. Omental, retroperitoneal, and mesocolonic fat was collected by ventral midline celiotomy; incisional nuchal ligament and tail head adipose tissue biopsy specimens were collected concurrently. The expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, plasminogen activator inhibitor-1 (PAI-1), and monocyte chemoattractant protein-1 (MCP-1) in each depot was measured by real-time quantitative polymerase chain reaction. Data were analyzed by 2-way analysis of variance for repeated measures (P<.05). RESULTS: No differences in TNF-alpha, IL-1beta, IL-6, PAI-1, or MCP-1 mRNA concentrations were noted between IR and IS groups for each depot. Concentrations of mRNA coding for IL-1beta (P=.0005) and IL-6 (P=.004) were significantly higher in nuchal ligament adipose tissue than in other depots. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that the nuchal ligament depot has unique biological behavior in the horse and is more likely to adopt an inflammatory phenotype than other depots examined. Visceral fat may not contribute to the pathogenesis of obesity-related disorders in the horse as in other species.

Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise.

REASON FOR PERFORMING STUDY: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. OBJECTIVES: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. METHODS: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatography-mass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. RESULTS: Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. CONCLUSIONS AND POTENTIAL RELEVANCE: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.

Effects of oral electrolyte supplementation on endurance horses competing in 80 km rides.

REASONS FOR PERFORMING STUDY: There is no evidence that use of oral electrolyte pastes enhances performance in competing endurance horses. OBJECTIVE: To ascertain whether oral administration of a high dose (HD) of sodium chloride (NaCl) and potassium chloride (KCl) to endurance horses would differentially increase water intake, attenuate bodyweight (bwt) loss and improve performance when compared to a low dose (LD). METHODS: A randomised, blinded, crossover study was conducted on 8 horses participating in two 80 km rides (same course, 28 days apart). Thirty minutes before and at 40 km of the first ride 4, horses received orally 02 g NaCl/kg bwt and 0.07 g KCl/kg bwt. The other 4 received 0.07 g NaCl/kg bwt and 0.02 g KCl/kg bwt. Horses received the alternate treatment in the second ride. Data were analysed with 2-way ANOVA for repeated measures (P<0.05). RESULTS: Estimated water intake was significantly greater with HD both at the 40 km mark and as total water intake; however, differences in bwt loss and speed between HD and LD were not found. Treatment significantly affected serum Na+, Cl-, HCO3, pH and water intake, but not serum K+ or bwt. Serum Na+ and Cl- were significantly higher at 80 km when horses received HD, but no differences were found in early recovery. Venous HCO3- and pH were significantly lower throughout the ride and in early recovery when horses received HD. CONCLUSIONS AND POTENTIAL RELEVANCE: Other than enhancing water intake, supplementing endurance horses with high doses of NaCI and KCl did not provide any detectable competitive advantage in 80 km rides. Further, the elevated serum electrolyte concentrations induced with HD might not be appropriate for endurance horses.

Effects of dietary glycaemic response after exercise on blood concentrations of substrates used indirectly for muscle glycogenesis.

REASONS FOR PERFORMING STUDY: Exercise depletes muscle glycogen stores, which could subsequently impair performance. Muscle glycogen replenishment is determined by substrate availability. OBJECTIVES: To study the effects of feeding meals of varying glycaemic responses on blood concentrations of substrates used for glycogenesis in horses with exercise-induced glycogen depletion. METHODS: In a 3-way crossover study, 7 horses received each of 3 isocaloric diets for 72 h after undergoing glycogen-depleting exercise: 1) a high soluble-carbohydrate diet, which induced a high-glycaemic (HGI) response; 2 and 3) a low soluble-carbohydrate or a mixed soluble-carbohydrate diet (control group), which both induced a similar low-to-moderate glycaemic (LGI) response. Muscle biopsies and venous samples were collected before and up to 72 h after exercise. RESULTS: Feeding HGI diet resulted in a higher (P<0.001) rate of muscle glycogenesis over 72 h compared to LGI diets. Plasma glycerol, triglyceride, lactate, serum NEFA and total protein concentrations, and haematocrit were significantly (P<0.001) higher after compared to before exercise. Whereas no significant overall dietary effect was observed on these metabolites over 72 h, there was a tendency for glycerol, NEFA and triglyceride concentrations to be lower for LGI compared to HGI diets over 6 h after exercise (P<0.05; 1, 6 and 4-6 h after exercise, respectively). CONCLUSIONS: These data suggest that horses fed LGI meals after exercise had limited lipid utilisation without any significant shift of substrate utilisation toward gluconeogenesis, which could have contributed to the slower rate of muscle glycogenesis compared to horses fed HGI diets.