Evaluation of a novel ambulatory electrocardiogram monitor (the Carnation Ambulatory Monitor) for use in horses.

INTRODUCTION: Short-term electrocardiogram (ECG) examinations of horses may not detect paroxysmal arrhythmias. Twenty-four hour Holter equipment can be unwieldy and inconvenient for long-term use. This study evaluated a novel long-term ECG patch recorder, the Carnation Ambulatory Monitor (CAM) in horses, determining ideal placement, practicality, durability and performance. ANIMALS: Twenty-one adult mixed-breed horses. METHODS: Prospective observational study. Three horses had ECG patches fitted at selected sites (phase 1); the two most promising sites were used for further wear testing (phase 2) and the best site was chosen for a trial in 18 horses (phase 3), 16 of which had presented for evaluation of cardiac disease. In phase 1, the CAM was compared with a standard telemetric ECG. The CAM ECGs were analysed using proprietary software. RESULTS: The most promising sites for CAM placement were the ventral midline caudal to the xiphisternum and left thorax caudal to the girth. The ventral midline was chosen for further evaluation. The CAM provided reliable and generally excellent ECG quality at rest (median quality score 4.5/5, range 3-5), over extended periods, allowing detection of arrhythmias. The ECG quality was poor during exercise (median quality score 1, range 1-5), except in three horses. In 15/17 placements in the standing horse, greater than 85% of the potential recording time was achieved. CONCLUSIONS: The CAM is a convenient and well-tolerated device for evaluating equine cardiac rhythm at rest over long periods. Further evaluation of the ideal placement site during exercise may increase its diagnostic utility.

Adipose tissue dysfunction in obese horses with equine metabolic syndrome.

BACKGROUND: Obesity is a common feature of equine metabolic syndrome (EMS). In other species, obese adipose tissue shows pathological features such as adipocyte hypertrophy, fibrosis, inflammation and impaired insulin signalling all of which contribute to whole body insulin dysregulation. Such adipose tissue dysfunction has not been investigated in horses. OBJECTIVES: To determine if obese horses with EMS have adipose tissue dysfunction characterised by adipocyte hypertrophy, fibrosis, inflammation and altered insulin signalling. STUDY DESIGN: Cross-sectional post-mortem study. METHODS: Samples of peri-renal (visceral) and retroperitoneal adipose tissue were obtained at post-mortem from healthy horses (n = 9) and horses with EMS (n = 6). Samples were analysed to determine average adipocyte size, fibrotic content and expression of inflammatory and insulin signalling genes. RESULTS: Horses with metabolic syndrome showed marked adipocyte hypertrophy and increased expression of adipokines (leptin) and inflammatory cytokines (TNFα, IL1ß and CCL2) in both adipose tissue depots compared to healthy horses. There were no differences in fibrosis or expression of genes relating to insulin signalling between the groups. MAIN LIMITATIONS: Cases used in this study had advanced EMS and may represent the end stage of the condition; the design of the study is such that we were unable to relate the identified adipose tissue dysfunction to whole body insulin dysregulation. CONCLUSIONS: Horses with obesity and EMS have significant dysfunction of the peri-renal and retroperitoneal adipose tissue that may contribute to whole body insulin dysregulation.

Neurodegeneration in equine grass sickness is not attributable to niacin deficiency.

BACKGROUND: The aetiology of equine grass sickness (EGS) is currently unknown. We hypothesised that an acute deficiency of niacin (vitamin B3), which plays a key role in neural homeostasis, may contribute to neurodegeneration in EGS. Niacin deficiency can potentially result from ingestion of niacin antagonists produced by pasture mycotoxigenic fungi. OBJECTIVES: To compare the niacin status of EGS and control grazing horses. A secondary objective was to compare blood concentrations of vitamins B1, B2 and B6 in EGS and control grazing horses to determine if the status of these vitamins was altered in EGS. STUDY DESIGN: Case-control study. METHODS: Indices of niacin status, namely the erythrocyte nicotinamide adenine dinucleotide:nicotinamide adenine dinucleotide phosphate ratio (NAD:NADP ratio) and erythrocyte concentrations of NAD and NADP, were compared in blood collected from EGS and healthy control grazing horses. Blood concentrations of vitamins B1, B2 and B6 were also compared. RESULTS: There was no significant intergroup difference in the NAD:NADP ratio, the main index of functional niacin status (control group: median 2.1, interquartile range [IQR] 1.8-2.6; EGS group: median 2.1, IQR 1.9-2.6). EGS horses had significantly higher (median value increased by 25%) concentrations of NADP. There were no intergroup differences in blood concentrations of vitamins B1, B2 and B6. MAIN LIMITATIONS: The interpretation of data was limited by the lack of previously defined equine reference ranges for many of the analytes. Sample size was low. CONCLUSIONS: Niacin deficiency does not contribute to EGS neurodegeneration.

Treatment of equine metabolic syndrome: A clinical case series.

REASONS FOR PERFORMING STUDY: Treatment of equine metabolic syndrome (EMS) is essential to improve insulin sensitivity and reduce the risk of laminitis. Calorie restriction and increased exercise are the mainstays of treatment but there is potential for poor owner compliance. OBJECTIVES: To determine whether significant weight loss accompanied by improvements in measures of insulin sensitivity can be achieved in horses and ponies with EMS managed by their owners in their normal environment under veterinary guidance. STUDY DESIGN: Retrospective clinical case series. METHODS: Horses and ponies attending 2 university hospitals for investigation and treatment of suspected EMS were eligible for inclusion in the study. Animals underwent a clinical examination, basal and dynamic endocrine testing; those with pituitary pars intermedia dysfunction (PPID) were excluded. Owners were given individually tailored diet and exercise programmes to follow for between 3 and 6 months. After the treatment period, clinical examination and endocrine tests were repeated and results compared to the initial assessment. RESULTS: Nineteen animals were recruited to the study, 17 with a history of laminitis. All animals showed a reduction in body condition score (P<0.001) and 18/19 had a reduction in bodyweight (P<0.001) between assessments. There were significant (P<0.05) reductions in basal insulin, insulin at 45 min during a combined glucose insulin tolerance test (CGIT), time for blood glucose concentration to return to baseline during a CGIT and mean area under the glucose curve. CONCLUSIONS: A diet and exercise programme tailored to the needs of the individual animal and implemented by the owner results in weight loss accompanied by improvements in insulin sensitivity.

Role of mechanical ventilation in the airborne transmission of infectious agents in buildings.

Infectious disease outbreaks and epidemics such as those due to SARS, influenza, measles, tuberculosis, and Middle East respiratory syndrome coronavirus have raised concern about the airborne transmission of pathogens in indoor environments. Significant gaps in knowledge still exist regarding the role of mechanical ventilation in airborne pathogen transmission. This review, prepared by a multidisciplinary group of researchers, focuses on summarizing the strengths and limitations of epidemiologic studies that specifically addressed the association of at least one heating, ventilating and/or air-conditioning (HVAC) system-related parameter with airborne disease transmission in buildings. The purpose of this literature review was to assess the quality and quantity of available data and to identify research needs. This review suggests that there is a need for well-designed observational and intervention studies in buildings with better HVAC system characterization and measurements of both airborne exposures and disease outcomes. Studies should also be designed so that they may be used in future quantitative meta-analyses.

Bodyweight change aids prediction of survival in chronic equine grass sickness.

REASONS FOR PERFORMING STUDY: Objective criteria for predicting survival of chronic grass sickness cases are currently lacking. OBJECTIVES: To determine whether the rate and/or magnitude of bodyweight change during hospitalisation of chronic grass sickness cases can provide an objective predictor of survival to discharge from hospital. Clinicians' recorded indication(s) for euthanasia were also reviewed. STUDY DESIGN: Single centre retrospective observational study. METHODS: Case records of all horses admitted for management of chronic grass sickness to The Dick Vet Equine Hospital between 1998 and 2013 were analysed. Case background, survival to hospital discharge, indication(s) for euthanasia, disease duration at admission and bodyweight changes during the hospitalisation period were analysed, and data for survivors and nonsurvivors compared. Percentage weight change was calculated for 7 day intervals up to 28 days (0-7, 7-14, 14-21, 21-28 days) and for entire periods from the first weight recorded (0-7, 0-14, 0-21, 0-28 days). These results were used to estimate survival probability conditional on weight change. RESULTS: The study sample comprised 213 horses, with 114 survivors (53.5%) and 99 (46.5%) nonsurvivors. Compared with nonsurvivors, survivors had significantly lower median maximum bodyweight loss as a percentage of first weight (survivors 5.9%, interquartile range 1.8-13.5; nonsurvivors 12.7%, 6.4-17.3). Throughout all time periods analysed, survivors had significantly lower median bodyweight loss than nonsurvivors, but no specific time period was more predictive of survival. Highest percentages of total bodyweight loss for individual horses were comparable for survivors (36%) and nonsurvivors (37%). Survival prediction curves reporting percentage survival rates for all time periods analysed provided data to aid prediction of chronic grass sickness survival. CONCLUSIONS: Overall, nonsurvivors had greater bodyweight loss than survivors. Rapidity and magnitude of bodyweight loss were equally predictive of outcome. Percentage survival prediction curves provide objective data to aid discussion of prognosis, but greater predictive specificity with associated sensitivity is required for clinical decision making in individual cases.

Short-term incubation of equine laminar veins with cortisol and insulin alters contractility in vitro: possible implications for the pathogenesis of equine laminitis.

This study investigated the effects of cortisol and insulin, hormones that affect both glycaemic status and vascular function, on the in vitro contractility of isolated healthy equine small laminar veins. Small veins (150-500 µm) draining the digital laminae from healthy horses or ponies were investigated by wire myography. Concentration response curves were constructed for noradrenaline (NA), phenylephrine (PE), endothelin-1 (ET-1) and 5-hydroxytryptamine (5-HT) in the presence of either cortisol (10(-6 ) m) or insulin (1000 µIU/mL). Cortisol significantly increased the maximum contractility of laminar veins to the vasoconstrictors NA and 5-HT but decreased the maximal contraction to ET-1. Insulin decreased the contractility of vessels to PE and ET-1. It is possible that short-term cortisol excess could enhance venoconstrictor responses to 5-HT and NA in laminar veins in vivo, thereby predisposing to laminitis. Additionally, a reduction in the ability of insulin to counteract alpha-adrenoreceptor and ET-1-mediated contraction, likely to occur in subjects with insulin resistance, may further exacerbate venoconstriction in animals prone to laminitis. These mechanisms may also predispose horses with disorders such as equine Cushing's disease and equine metabolic syndrome to laminitis.

European outbreaks of atypical myopathy in grazing horses (2006-2009): determination of indicators for risk and prognostic factors.

REASONS FOR PERFORMING STUDY: Appropriate management of atypical myopathy (AM) requires the establishment of an accurate diagnosis and prognosis. Furthermore, preventive measures to avoid AM need to be refined. OBJECTIVES: The aims of the study were as follows: 1) to improve the diagnosis of AM; 2) to identify prognostic predictors; and 3) to refine recommended preventive measures based on indicators of risk factors. METHODS: An exploratory analysis of cases in Europe between 2006 and 2009 reported to the Atypical Myopathy Alert Group was conducted. Based on clinical data, reported cases were allocated into 2 groups: confirmed or highly probable AM (AM group; further divided into survivors and nonsurvivors); and cases with a low probability of having AM or with another final diagnosis (non-AM group). Using Welch's test and odds ratios corrected for multiple comparisons, the AM vs. non-AM groups were compared to identify indicators for diagnosis and risk factors, and survivors vs. nonsurvivors in the AM group were compared to identify prognostic factors. Sensitivity, specificity and positive and negative predictive values were calculated for specific clinical signs related to final diagnosis and outcome. RESULTS: From 600 reported cases, 354 AM cases (survival rate of 26%) and 69 non-AM cases were identified, while there were insufficient data to categorise the remainder. Variables valuable for diagnosing AM compared with similar diseases were as follows: presence of dead leaves and wood and/or trees on pastures; sloping pastures; full-time pasture access; no food supplementation; normal body condition; pigmenturia; normothermia; and congested mucous membranes. Nonsurvival was associated with recumbency, sweating, anorexia, dyspnoea, tachypnoea and/or tachycardia. Survival was associated with remaining standing most of the time, normothermia, normal mucous membranes, defaecation and vitamin and antioxidant therapy. CONCLUSIONS AND POTENTIAL RELEVANCE: This study refines the list of risk factors for AM. Clinical signs valuable for diagnosis and prognosis have been identified, enabling clinicians to improve management of AM cases.

European outbreaks of atypical myopathy in grazing equids (2006-2009): spatiotemporal distribution, history and clinical features.

REASONS FOR PERFORMING STUDY: Improved understanding of the epidemiology of atypical myopathy (AM) will help to define the environmental factors that permit or support the causal agent(s) to exert toxicity. OBJECTIVES: This European survey of AM aimed to describe spatiotemporal distribution, survival, clinical signs, circumstances in which AM develops and its different expressions between countries and over time. METHODS: The spatiotemporal distribution, history and clinical features of AM cases reported to the Atypical Myopathy Alert Group from 2006 to 2009 were described. Comparisons of data from the most severely affected countries and from the large outbreaks were made with Fisher's exact and Welch's tests with Bonferroni correction. RESULTS: Of 600 suspected cases, 354 met the diagnostic criteria for confirmed or highly probable AM. The largest outbreaks occurred during the autumns of 2006 and 2009 in Belgium, France and Germany. For the first time, donkeys, zebras and old horses were affected, and clinical signs such as gastrointestinal impaction, diarrhoea, penile prolapse, buccal ulceration and renal dysfunction were observed. Affected horses spent >6 h/day on pastures that almost always contained or were surrounded by trees. The latency period was estimated at up to 4 days. Overall survival rate was 26%. Although differences between countries in affected breeds, body condition, horse management and pasture characteristics were recognised, the common presenting clinical signs and mortality were similar between countries. CONCLUSIONS AND POTENTIAL RELEVANCE: This study describes new data on case details, history and clinical course of AM that is of preventive, diagnostic and therapeutic value. However, the true impact of the findings of this study on the development of or severity of AM should be tested with case-control studies.

Retrospective evaluation of episodic collapse in the horse in a referred population: 25 cases (1995-2009).

BACKGROUND: Episodic collapse in horses has equine welfare and human safety implications. There are, however, no published case series describing this syndrome. OBJECTIVES: To characterize the cause and outcomes for horses referred for investigation of episodic collapse. ANIMALS: Twenty-five horses referred for investigation of single or multiple episodes of collapse. METHODS: Retrospective study. Clinical records from the Dick Vet Equine Hospital, University of Edinburgh from November 1995 to July 2009 were searched using the following keywords: collapse, collapsing, fall, syncope. Collapse was defined as an incident in which the horse lost postural tone with or without progression to recumbency and with or without loss of consciousness. Long-term follow-up information was obtained by telephone conversation with the owner. RESULTS: A final diagnosis was reached in 11 cases, namely cardiac arrhythmia (4), right-sided heart failure (1), hypoglycemia (2), generalized seizures (2), and sleep disorder (2). A presumptive diagnosis was reached in 8 cases, namely neurocardiogenic syncope (5), exercise-induced pulmonary hemorrhage (2), and generalized seizures (1). No diagnosis was reached in 6 cases despite comprehensive investigations. Three horses were euthanized at presentation. Treatment was attempted in 9 horses with 6 cases having successful outcome before discharge. Follow-up information was available for 14 of 19 horses discharged from the hospital. Only 1 of these horses was observed to collapse after discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Definitive diagnosis was more likely to be reached in cases with multiple episodes of collapse. Horses in which 1 episode of collapse occurred did not necessarily collapse again.

Study of the short- and long-term outcomes of 65 horses with peritonitis.

The records of 65 horses with peritonitis examined at two UK referral centres over a period of 12 years were reviewed. Peritonitis was defined in terms of the horse's peritoneal fluid containing more than 5 x 10(9) nucleated cells/l. Horses that had developed peritonitis after abdominal surgery or a rupture of the gastrointestinal tract were excluded. Of the 65 horses, 56 (86 per cent) survived to be discharged. Follow-up information was obtained from practice records and telephone calls to the owners for 38 of the horses. Of these, 32 (84 per cent) had survived for at least 12 months and were considered to be long-term survivors; the others six were euthanased within 12 months. Thirteen (34 per cent) of the horses discharged had experienced complications that could have been sequelae to peritonitis and eight of the 13 were euthanased. The cause of the peritonitis was identified in 15 cases; survival rates were lowest in horses with peritonitis secondary to urinary tract involvement or intra-abdominal masses. Of the other 50 cases, 47 (94 per cent) survived to discharge, but two were euthanased owing to recurrent colic.

Endothelin mediated contraction of equine laminar veins.

REASONS FOR PERFORMING STUDY: Endothelin-1 (ET-1) may be a key mediator in the pathogenesis of laminitis, but endothelin-mediated responses in the venous microcirculation of the equine foot have yet to be fully characterised. OBJECTIVES: To characterise the response of equine laminar veins to ET-1 and evaluate the ET-1 receptor subtypes that mediate this response. METHODS: Small veins (150-500 microns) draining the equine digital laminae from healthy horses and ponies subjected to euthanasia at an abattoir were investigated using wire myography. Concentration response curves were constructed for ET-1 in the presence of ETA (BQ123) and ETB (BQ788) receptor antagonists, and L-NAME, a nitric oxide synthase blocker. The selective ETB receptor agonist BQ3020 was investigated alone and following incubation with L-NAME, with or without BQ788. RESULTS: Endothelin-1 contraction of laminar veins was significantly inhibited by BQ123 but not by BQ788. In the presence of L-NAME, sensitivity of laminar veins to ET-1 was enhanced 4-fold, and further addition of BQ788 did not alter this increased sensitivity. BQ3020 induced no venoconstriction; however, in the presence of L-NAME, it caused contraction of veins with approximately 30% of the efficacy of ET-1. The action of BQ3020 in the presence of L-NAME was abolished by BQ788. CONCLUSIONS: Both ETA and ETB receptors are involved in the net tonic response to ET-1 in normal laminar veins. A population of ETB receptors may be present on the vascular endothelium and on smooth muscle of laminar veins, and the action of ET-1 at these 2 sites is likely to be approximately equal and opposite. POTENTIAL RELEVANCE: Our results clarify the function of the ET-1 receptor subtypes in laminar veins from healthy horses. Further study of ET-1 receptors in laminitic horses is therefore warranted.

Use of intravenous flecainide in horses with naturally-occurring atrial fibrillation.

REASONS FOR PERFORMING STUDY: It has been reported that i.v. flecainide has a high efficacy for the treatment of experimentally-induced acute atrial fibrillation (AF) in horses and that its use is associated with minimal toxic side effects. OBJECTIVES: The objectives were to study the efficacy of i.v. flecainide as a treatment for atrial fibrillation in horses with naturally-occurring AF. METHODS: Ten horses with naturally-occurring AF were treated with 2 mg/kg bwt flecainide i.v. at a rate of 0.2 mg/kg bwt/min. In 3 horses, the infusion was continued at 0.05-0.10 mg/kg bwt/min until a total dose of 3.0 mg/kg bwt had been administered. Heart rate, QRS duration and average interval between fibrillation waves were measured before, during and following flecainide infusion. If conversion to normal sinus rhythm was not achieved, horses were treated with quinidine sulphate per os at a dose of 22 mg/kg bwt given every 2 h. RESULTS: None of the horses with chronic AF (n = 9) converted to sinus rhythm with flecainide i.v. The only horse treated successfully had acute AF of 12 days' duration. The QRS duration and fibrillation cycle length increased significantly (P = 0.006 and 0.002, respectively) during and following flecainide infusion. Heart rate did not increase significantly over time however, 3 horses developed heart rates in excess of 100 beats/min. Two horses developed a potentially dangerous ventricular dysrhythmia during the first 15 mins of treatment. Quinidine sulphate given per os restored sinus rhythm in 8 out of 9 horses, with minimal adverse effects. CONCLUSIONS: Although flecainide might be efficacious in cases of acute AF, it was not possible to restore sinus rhythm in horses with naturally-occurring chronic AF at the dosages used in this study. In 2 horses, 2.0 mg/kg bwt flecainide was associated with potentially dangerous dysrhythmias. POTENTIAL CLINICAL RELEVANCE: Intravenous administration of 2 mg/kg bwt flecainide is unlikely to convert chronic AF in horses and could induce dangerous dysrhythmias.

Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses with equine Cushing's disease.

REASONS FOR PERFORMING STUDY: The mechanisms underlying the increased risk of laminitis in horses with equine Cushing's disease (ECD) are poorly understood. HYPOTHESIS: That abnormalities in glucose homeostasis, similar to those which cause microvascular dysfunction in human diabetics, contribute to development of laminitis in horses with ECD. METHODS: Thirty-one aged horses were divided into 3 groups based on clinical signs and dexamethasone suppression testing (DST). Group 1 (n = 12) had clinical ECD as evidenced by hirsutism. Group 2 (n = 10) had a positive DST but no hirsutism. Group 3 (n = 9) were controls without ECD, with a negative DST and no clinical evidence of ECD. Biochemical indices of glucose metabolism, vascular function and oxidative stress were determined in single morning blood samples. RESULTS: Group 1 had abnormalities in glucose homeostasis, including increased levels of glucose and insulin, compared to Groups 2 and 3. Groups 1 and 2 had significantly lower plasma thiol (PSH) levels and nonsignificantly lower albumin-corrected PSH levels than Group 3, consistent with oxidative stress. CONCLUSIONS AND POTENTIAL RELEVANCE: The observed abnormalities in glucose metabolism and oxidative stress could potentially contribute to development of laminitis in horses with ECD, by similar mechanisms to those that cause microvascular dysfunction in human diabetics. The absence of inter-group differences in the biochemical indices of vascular function precludes their use as preclinical diagnostic indicators of vascular dysfunction. The study also highlighted limitations in the premortem diagnosis of ECD.