Effects of trimethoprim-sulfadiazine and detomidine on the function of equine Kv 11.1 channels in a two-electrode voltage-clamp (TEVC) oocyte model.

The long QT syndrome (LQTS) is a channelopathy that can lead to severe arrhythmia and sudden cardiac death. Pharmacologically induced LQTS is caused by interaction between drugs and potassium channels, especially the Kv 11.1 channel. Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine. However, some compounds, such as trimethoprim-sulfonamide combinations are still widely used in veterinarian medicine. Therefore, we investigate the effect of trimethoprim-sulfadiazine (TMS), trimethoprim, sulfadiazine, and detomidine on equine-specific Kv 11.1 channels. Kv 11.1 channels cloned from equine hearts were heterologously expressed in Xenopus laevis oocytes, and whole cell currents were measured by two-electrode voltage-clamp before and after drug application. TMS blocked equine Kv 11.1 current with an IC50 of 3.74 mm (95% CI: 2.95-4.73 mm) and affected the kinetics of activation and inactivation. Similar was found for trimethoprim but not for sulfadiazine, suggesting the effect is due to trimethoprim. Detomidine did not affect equine Kv 11.1 current. Thus, equine Kv 11.1 channels are also susceptible to pharmacological block, indicating that some drugs may have the potential to affect repolarization in horse. However, in vivo studies are needed to assess the potential risk of these drugs to induce equine LQTS.

Relationships between body dimensions, body weight, age, gender, breed and echocardiographic dimensions in young endurance horses.

BACKGROUND: The heart's physiological adaptation to aerobic training leads to an increase in heart chamber size, and is referred to as the Athlete's heart. However, heart dimensions are also related to body weight (BWT), body size, growth and (in some species) breed. There are few published data on the relationships between heart dimensions and growth or aerobic training in Arabian and Arabian-related endurance horses. Therefore the objective of the present study was to describe the influence of body dimensions (body length (BL), thoracic circumference (TC), withers height (WH)), BWT, age, gender, breed (purebred Arabians, part-bred Arabians, Anglo-Arabians, and Others) and the initiation of endurance training on echocardiographic measurements in competition-fit endurance horses aged 4 to 6 years. RESULTS: Most left atrial (LA) and left ventricular (LV) dimensions increased with age, whereas LA and LV functional indices did not. Although there was no gender difference for LV dimensions, females had larger LA dimensions. In terms of breed, Anglo-Arabians had the largest LV dimensions. Regression models indicated that the included explanatory factors had a weak influence on heart dimensions. Age, body dimensions, breed and gender showed the most consistent influence on LA dimensions, whereas BWT, breed and kilometres covered in competition showed the most consistent influence on LV dimensions. CONCLUSION: The increase in echocardiographic dimensions with age indicates on-going growth in our population of 4 to 6 year-old horses. We also observed small changes associated with the initiation of endurance training. Morphometric dimensions had a greater influence on LA dimensions, whereas LV dimensions were also influenced (albeit weakly) by parameters associated with exercise intensity. These results may therefore reflect early adaptations linked to the initiation of endurance training.

Differences in the electrocardiographic QT interval of various breeds of athletic horses during rest and exercise.

OBJECTIVES: Quantitative measurements of cardiac repolarization, defined as the electrocardiographic QT interval, have important diagnostic implications in humans, as irregularities can trigger potentially fatal ventricular tachyarrhythmia. In both humans and horses, cardiac repolarization is influenced to some extent by heart rate, age, body weight (BW), sex, autonomic tone, and environment. In horses, there is substantial inter-breed variation in size and training, and the aims of this study were therefore to determine the best model describing the QT to RR relationship in breeds of various athletic horses and to test for differences in the QT interval. ANIMALS: Ten Icelandic horses, 10 Arabian horses, 10 Thoroughbreds, 10 Standardbreds, six Coldblood trotters, 10 Warmbloods (dressage) and 10 Warmbloods (show jumping). All horses were geldings. METHODS: QT intervals were measured from resting to peak exercise level and plotted against RR intervals. Data points were fitted with relevant regression models, and the effect of breed, BW, and estimated exercise intensity was examined. RESULTS: For all breeds in this study, the QT interval was best described as a function of RR by the piecewise linear regression model. The breed of horse had a significant effect on the model. There was no systematic effect of BW or estimated exercise intensity, but a high inter-horse variability was observed. CONCLUSIONS: The equine QT interval should preferably be corrected for heart rate according to breed. In addition, the results indicate that equine studies of the QT interval must be designed to eliminate the influence of a large inter-horse variation.

Analytic validation and comparison of three commercial immunoassays for measurement of plasma atrial/A-type natriuretic peptide concentration in horses.

Measurement of atrial/A-type natriuretic peptide (ANP) concentrations may be of use for assessment of cardiac disease, and reliable data on the analytic performance of available assays are needed. To assess the suitability for clinical use of commercially available ANP assays, intra-assay and inter-assay coefficient of variation and dilution parallelism were calculated for three immunoassays (RIAPen, RIAPhoen, and an ELISAPen) using blood samples from healthy and diseased horses to cover a wide range of ANP concentrations. Further, agreement between assays was assessed using linear regression and Bland-Altman analyses. For all assays, precision was moderate but acceptable and dilution parallelism was good. All assays showed analytic performance similar to other immunoassays used in veterinary medicine. However, the results from the three assays were poorly comparable. Our study highlights the need for an optimised species-specific assay for equine samples.

Plasma atrial natriuretic peptide concentrations in horses with heart disease: a pilot study.

Atrial natriuretic peptide (ANP) is a cardiovascular biomarker that might be useful in assessing the severity of cardiac disease in horses. Plasma ANP concentrations (Cp(ANP)) were compared between horses with heart disease but normal chamber size and function (Group A; n=6), horses with heart disease associated with left atrial (LA) enlargement, LA dysfunction, and/or left ventricular (LV) enlargement (Group B; n=5), and horses with no clinically apparent cardiovascular disease (Group C; n=13). The median (min-max) for Cp(ANP) was significantly higher in Group B (53.5 (36.0-70.7) pg/mL), compared to Group A (12.5 (6.3-19.8) pg/mL) and Group C (13.4 (7.2-34.0) pg/mL). Backwards stepwise multiple linear regression showed that Cp(ANP) in horses with heart disease was related to LA dimensions, but not to LV size, LA function, and LV function. The results indicated that Cp(ANP) in horses might be useful in detecting LA enlargement and that Cp(ANP) could be related to the severity of cardiac disease. Larger prospective studies are necessary to confirm these results.

Performance parameters and post exercise heart rate recovery in Warmblood sports horses of different performance levels.

REASONS FOR PERFORMING STUDY: Standardised exercise tests are used for fitness evaluation of sports horses. Standards are described for Thoroughbreds and Standardbreds; however, limited information is available for Warmbloods. OBJECTIVES: To establish normative standards of performance parameters and heart rate recovery (HRR) in Warmblood riding horses of different levels of fitness using a submaximal incremental exercise test (SIET) performed on a treadmill. METHODS: A SIET was carried out with 29 healthy and treadmill-accustomed Warmbloods: eleven 3-day event horses (TDE) and 18 horses from the National Equestrian Centre (NEC) competing in amateur jumping and/or dressage events. After a warm-up phase, horses performed 2 stages at trot and 3-5 stages at gallop at 6% incline. The first stage lasted 120 s, all others 90 s. Velocity (V) and heart rate (HR) were measured continuously and blood lactate concentration (LAC) at the end of each exercise stage. V at HR 150 and 200 beats/min (V(150), V(200)), V and HR at 2 and 4 mmol/l LAC (V(2), V(4) and HR(2), HR(4), respectively) were calculated and compared between discipline groups. For reference values, horses were divided on the basis of the V(4) -results in good (GP) and average performers (AP) (performance groups). Five minute passive HRR was compared between performance groups. Fifteen NEC horses were retested within 1-3 months. Groups were compared with t tests and P < 0.05 considered significant. RESULTS: Three-day event horses had higher V(150), V(2) and V(4) values than NEC. GP had higher values in all performance parameters compared to AP. No differences were found between test and retest. GP mean recovery HR was different from that of AP from 120 s of recovery onwards. CONCLUSION: Treadmill SIETs are suitable to objectify aerobic capacity in Warmblood riding horses. Normative standards were assessed for well and averagely-trained horses. The results can be referred to when diagnosing patients with exercise intolerance.

Observer agreement for detection of cardiac arrhythmias on telemetric ECG recordings obtained at rest, during and after exercise in 10 Warmblood horses.

REASONS FOR PERFORMING STUDY: Frequent supraventricular or ventricular arrhythmias during and after exercise are considered pathological in horses. Prevalence of arrhythmias seen in apparently healthy horses is still a matter of debate and may depend on breed, athletic condition and exercise intensity. OBJECTIVES: To determine intra- and interobserver agreement for detection of arrhythmias at rest, during and after exercise using a telemetric electrocardiography device. MATERIALS AND METHODS: The electrocardiogram (ECG) recordings of 10 healthy Warmblood horses (5 of which had an intracardiac catheter in place) undergoing a standardised treadmill exercise test were analysed at rest (R), during warm-up (W), during exercise (E), as well as during 0-5 min (PE(0-5)) and 6-45 min (PE(6-45)) recovery after exercise. The number and time of occurrence of physiological and pathological 'rhythm events' were recorded. Events were classified according to origin and mode of conduction. The agreement of 3 independent, blinded observers with different experience in ECG reading was estimated considering time of occurrence and classification of events. RESULTS: For correct timing and classification, intraobserver agreement for observer 1 was 97% (R), 100% (W), 20% (E), 82% (PE(0-5)) and 100% (PE(6-45)). Interobserver agreement between observer 1 vs. observer 2 and between observer 1 vs. 3, respectively, was 96 and 92.6% (R), 83 and 31% (W), 0 and 13% (E), 23 and 18% (PE(0-5)), and 67 and 55% (PE(6-45)). When including the events with correct timing but disagreement for classification, the intraobserver agreement increased to 94% during PE(0-5) and the interobserver agreement reached 83 and 50% (W), 20 and 50% (E), 41 and 47% (PE(0-5)), and 83.5 and 65% (PE(6-45)). The interobserver agreement increased with observer experience. CONCLUSIONS: Intra- and interobserver agreement for recognition and classification of events was good at R, but poor during E and poor-moderate during recovery periods. These results highlight the limitations of stress ECG in horses and the need for high-quality recordings and adequate observer training.

[Diagnostic workup of chronic inflammatory bowel disease in the horse]. / Diagnostische Aufarbeitung der chronischen Darmentzündung beim Pferd.

The present retrospective study describes the diagnostic workup and collected findings in 7 horses with chronic inflammatory bowel disease over the years 2000-2006. The diagnosis could be confirmed histologically with biopsies taken during laparoscopy or laparotomy or during post mortem examination. Weight loss and chronic diarrhoea were the most commonly reported clinical findings. Among ancillary examinations (fecal analysis, gastroscopy, abdominal ultrasonography, rectal mucosal biopsy) the D-xylose absorption test provided the most useful information. Although clinical signs and laboratory findings are helpful diagnostic tools, a definitive diagnosis is only possible by histological analysis of the intestinal segment.