Publications by authors named "Rikke Buhl"

39 Publications

Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes.

Circ Res 2021 Apr 14. Epub 2021 Apr 14.

Cardiovascular Sciences, University of Manchester, UNITED KINGDOM.

Athletes present with atrioventricular node (AV node) dysfunction manifesting as AV block. This can necessitate electronic pacemaker implantation, known to be more frequent in athletes with a long training history. AV block in athletes is attributed to high vagal tone. Here we investigated the alternative hypothesis that electrical remodeling of the AV node is responsible. Radio-telemetry ECG data and AV node biopsies were collected in sedentary and trained Standardbred racehorses, a large-animal model of the athlete's heart. Trained horses presented with longer PR intervals (that persisted under complete autonomic block) versus sedentary horses, concomitant with reduced expression of key ion channels involved in AV node conduction: L-type Ca2+ channel subunit CaV1.2 and the hyperpolarization-activated cyclic nucleotide gated channel 4 (HCN4). AV node electrophysiology was explored further in mice; prolongation of the PR interval (in vivo and ex vivo), Wenckebach cycle length and AV node refractory period was observed in mice trained by swimming versus sedentary mice. Transcriptional profiling in laser-capture microdissected AV node revealed striking reduction in pacemaking ion channels in trained mice, translating into protein downregulation of CaV1.2 and HCN4. Correspondingly, patch clamp recordings in isolated AV node myocytes demonstrated a training-induced reduction in ICa,L and If density that likely contributed to the observed lower frequency of action potential firing in trained cohorts. microRNA (miR) profiling and in vitro studies revealed miR-211-5p and miR-432 as direct regulators of CaV1.2 and HCN4. In vivo miRs suppression or detraining restored training-induced PR prolongation and ion channel remodeling. Training-induced AV node dysfunction is underscored by likely miR-mediated transcriptional remodeling that translates into reduced current density of key ionic currents involved in impulse generation and conduction. We conclude that electrical remodeling is a key mechanism underlying AV block in athletes.
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http://dx.doi.org/10.1161/CIRCRESAHA.119.316386DOI Listing
April 2021

Inhibition of Small-Conductance Calcium-Activated Potassium Current () Leads to Differential Atrial Electrophysiological Effects in a Horse Model of Persistent Atrial Fibrillation.

Front Physiol 2021 9;12:614483. Epub 2021 Feb 9.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.

Background: Small-conductance Ca-activated K (K2) channels have been proposed as a possible atrial-selective target to pharmacologically terminate atrial fibrillation (AF) and to maintain sinus rhythm. However, it has been hypothesized that the importance of the K2 current-and thereby the efficacy of small-conductance Ca-activated K current () inhibition-might be negatively related to AF duration and the extent of AF-induced remodeling.

Experimental Approach And Methods: To address the hypothesis of the efficacy of inhibition being dependent on AF duration, the anti-arrhythmic properties of the inhibitor NS8593 (5 mg/kg) and its influence on atrial conduction were studied using epicardial high-density contact mapping in horses with persistent AF. Eleven Standardbred mares with tachypacing-induced persistent AF (42 ± 5 days of AF) were studied in an open-chest experiment. Unipolar AF electrograms were recorded and isochronal high-density maps analyzed to allow for the reconstruction of wave patterns and changes in electrophysiological parameters, such as atrial conduction velocity and AF cycle length. Atrial anti-arrhythmic properties and adverse effects of NS8593 on ventricular electrophysiology were evaluated by continuous surface ECG monitoring.

Results: inhibition by NS8593 administered intravenously had divergent effects on right and left AF complexity and propagation properties in this equine model of persistent AF. Despite global prolongation of AF cycle length, a slowing of conduction in the right atrium led to increased anisotropy and electrical dissociation, thus increasing AF complexity. In contrast, there was no significant change in AF complexity in the LA, and cardioversion of AF was not achieved.

Conclusions: Intra-atrial heterogeneity in response to inhibition by NS8593 was observed. The investigated dose of NS8593 increased the AF cycle length but was not sufficient to induce cardioversion. In terms of propagation properties during AF, inhibition by NS8593 led to divergent effects in the right and left atrium. This divergent behavior may have impeded the cardioversion success.
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http://dx.doi.org/10.3389/fphys.2021.614483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900437PMC
February 2021

Evaluation of electrocardiographic repolarization parameters after administration of trimethoprim-sulfadiazine, detomidine, or their combination in horses.

Am J Vet Res 2021 Mar;82(3):207-217

Objective: To determine whether administration of trimethoprim-sulfadiazine (TMS), detomidine (DET), or TMS plus DET would be associated with changes in ECG repolarization parameters in horses.

Animals: 9 healthy adult horses.

Procedures: Each horse received 4 treatments in a blinded, randomized, crossover study design as follows: TMS, 16 to 24 mg/kg, IV; DET, 0.015 to 0.02 mg/kg, IV; TMS plus DET; and saline (0.9% NaCl) solution. Surface ECG traces were obtained over 24 hours, and repolarization parameters were measured at predefined time points after each treatment and compared with a 2-way ANOVA for repeated measures.

Results: Heart rate-corrected QT intervals (QTc) were significantly increased after administration of DET (mean ± SD difference in QTc, 36.57 ± 23.07 milliseconds; increase of 7%) and TMS plus DET (44.96 ± 29.16 milliseconds; increase of 9%), compared with baseline (before treatment) values and values after administration of saline solution. Saline solution and TMS alone did not affect QTc.

Conclusions And Clinical Relevance: Administration of DET or TMS plus DET was associated with a significant and possibly clinically relevant prolongation of QTc, with prolongation of 7% to 9%, a range that is considered as a risk factor for the development of cardiac arrhythmias in people. Results were unexpected because DET is considered to be a safe sedative for horses.
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http://dx.doi.org/10.2460/ajvr.82.3.207DOI Listing
March 2021

Antiarrhythmic investigations in large animal models of atrial fibrillation.

Br J Pharmacol 2021 Feb 24. Epub 2021 Feb 24.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, DK-2630, Taastrup, Denmark.

Atrial fibrillation (AF) constitutes an increasing health problem in the aging population. Animal models reflecting human phenotypes are needed to understand the mechanisms of AF, as well as to test new pharmacological interventions. In recent years, a number of large animal models, primarily pigs, goats, dogs and horses, have been used in AF research. These animals can to a certain extent recapitulate the human pathophysiological characteristics, and serve as valuable tools in investigating new pharmacological interventions for treating AF. This review focus on antiarrhythmic investigations in large animals. Initially spontaneous AF in small and large mammals are discussed. This is followed by a short presentation of frequently used methods for inducing short and long-term AF. The major focus of the review is on antiarrhythmic compounds either frequently used in the human clinic (ranolazine, flecainide, vernakalant and amiodarone) or being promising new AF medicine candidates (I , I and I blockers).
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http://dx.doi.org/10.1111/bph.15417DOI Listing
February 2021

Atrial fibrillation in horses Part 2: Diagnosis, treatment and prognosis.

Vet J 2021 Feb 22;268:105594. Epub 2020 Dec 22.

Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Belgium.

Atrial fibrillation (AF) is suspected by an irregularly irregular rhythm during auscultation at rest and should be confirmed by electrocardiography. Heart rate monitoring is potentially interesting for AF detection by horse owners, based on the disproportionally high heart rate during exercise or increased heart rate variability. Echocardiography and laboratory analysis are useful to identify underlying cardiac disease. Horses with severe cardiac disease should not undergo cardioversion due to the risk of recurrence. Cardioversion is recommended especially in horses performing high intensity exercise or showing average maximal heart rates higher than 220 beats per min or abnormal ventricular complexes during exercise or stress. Pharmacological cardioversion can be performed using quinidine sulphate administered orally, with an overall mean reported success rate around 80%. Other therapeutic drugs have been described such as flecainide, amiodarone or novel atrial specific compounds. Transvenous electrical cardioversion (TVEC) is performed by delivering a shock between two cardioversion catheters positioned in the left pulmonary artery and right atrium, with a success rate of >95%. After cardioversion, most horses return to their previous level of performance. However, the recurrence rate after pharmacological or electrical cardioversion is up to 39%. Recurrence has been related to previous unsuccessful treatment attempts, valvular regurgitation and the presence of atrial premature depolarisations or low atrial contractile function after cardioversion. Large atrial size and long AF duration have also been suggested as risk factors. Different approaches for preventing recurrence have been described such as the administration of sotalol, however, large clinical studies have not been published.
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http://dx.doi.org/10.1016/j.tvjl.2020.105594DOI Listing
February 2021

Thoracotomy and Pericardiotomy for Access to the Heart in Horses: Surgical Procedure and Effects on Anesthetic Variables.

J Equine Vet Sci 2021 Jan 31;96:103315. Epub 2020 Oct 31.

Faculty of Health and Medical Sciences, Department of Veterinary Clinical Sciences, University of Copenhagen, Taastrup, Denmark.

Thoracotomy is an uncommon procedure in horses but remains essential in a variety of cases of pleuropneumonia, pericarditis, thoracic trauma or diaphragmatic herniation, and for experimental thoracic and cardiac procedures. This study aimed at developing an experimental surgical procedure allowing access to the entire circumference of the heart and describing the effect of thoracotomy on pulmonary gas exchange in these horses. The study consisted of two arms, arm one (undergoing thoracotomy), was a terminal experimental study that included 11 Standardbred horses with experimentally induced (by tachypacing) atrial fibrillation. Arm two consisted of 6 Standardbred horses undergoing anesthesia for reasons unrelated to the present study. These horses functioned as controls. Anesthesia was induced using zolazepam and tiletamine. Anesthesia was maintained with isoflurane in 100% oxygen and ventilation with intermittent positive pressure (IPPV); no positive end-expiratory pressure (PEEP) was performed. Rib resection and pericardiotomy were performed for complete exposure of the entire circumference of the heart. Arterial blood samples were collected prior to, 5 and 30 minutes after puncture of pleura parietalis. In 10 horses, resection of the fifth rib was adequate for exposure of the heart. In one horse, removal of the sixth rib was also necessary. The duration of the surgical procedure (thoracotomy, pericardiotomy) was < 45 minutes. During a thoracotomy, PaO decreased significantly (P < .05) from 291.8 ± 82.8 mmHg to 165.2 ± 73.5 mmHg but was not different from normal anesthetized controls. The PaCO remained within normal limits. This surgical approach provided access to the entire circumference of the heart.
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http://dx.doi.org/10.1016/j.jevs.2020.103315DOI Listing
January 2021

A novel approach for obtaining 12-lead electrocardiograms in horses.

J Vet Intern Med 2021 Jan 4;35(1):521-531. Epub 2020 Dec 4.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.

Background: In equine medicine, 12-lead electrocardiograms (ECGs) rarely are used, which may in part be a result of shortcomings in the existing guidelines for obtaining 12-lead ECGs in horses. The guidelines recommend placing the limb leads on the extremities, which is inappropriate because the ventricular mean electrical axis is then perpendicular to the limb leads, leading to large variations in ECG configuration even among healthy horses. From an electrophysiological point of view, the leads instead should be parallel to the electrical axis to minimize variability.

Objective: Develop an improved method for obtaining 12-lead ECGs in horses based on electrophysiology and cardiac electrical vectors relevant to horses.

Animals: Thirty-five healthy Standardbred horses.

Methods: Two ECGs obtained at rest; 1 ECG with the electrodes placed according to the method developed in the present study, the Copenhagen method, and 1 ECG following existing guidelines.

Results: In the Copenhagen method, we repositioned the limb electrodes to the thorax to better capture the electrical activity of the heart. Variation in the mean electrical axis decreased dramatically with the Copenhagen method (SD decreased from 24.6° to 1.6°, P < .001). Consequently, this new method provided stable ECGs with repeatable configurations.

Conclusions And Clinical Importance: With this novel method, the ECG is recorded with respect to the electric axis to fully realize the potential of 12-lead ECG in horses. The Copenhagen method delivered more consistent and reliable ECG recordings compared to existing guidelines. The Copenhagen method potentially allows for expanded use of 12-lead ECGs in equine medicine.
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http://dx.doi.org/10.1111/jvim.15980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848388PMC
January 2021

Implantable loop recorders can detect paroxysmal atrial fibrillation in Standardbred racehorses with intermittent poor performance.

Equine Vet J 2020 Oct 28. Epub 2020 Oct 28.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Limited information is available on paroxysmal atrial fibrillation (PAF) in the horse. Indeed, undiagnosed PAF could result in poor performance. Due to the intermittent occurrence, PAF is difficult to diagnose. However, implanting a small ECG device (implantable loop recorder, ILR) subcutaneously, allows the continuous and automatic detection of PAF.

Objectives: The aim was to investigate the potential of ILRs as a tool for diagnosing PAF in horses with poor performance.

Study Design: Prospective field study.

Methods: Twelve racing Standardbred trotters with intermittent reduced performance (mean age: six years) were enrolled prospectively. The ILR was implanted subcutaneously at the fifth or sixth left intercostal space and data from the ILR was collected during the study period in which the horses were followed for a median duration of 7.5 month (range 6-28).

Results: The ILR was able to detect PAF in four out of twelve racehorses. The ILR also detected sustained atrial fibrillation (AF) in one horse during the study. The ILRs rely on RR detection and R waves were correctly identified in 96%. One hundred episodes were categorised as AF by the ILRs and subsequently visual ECG inspection categorised 12 as sinus rhythm (SR), 28 as sinus arrhythmia (SA), 14 as other arrhythmias and 46 as AF episodes. The Root Mean Square of the Successive Differences (RMSSD) values were significantly increased for AF compared to SR and SA.

Main Limitations: Few horses included and duration of study period varied among the horses. Further it was not possible to assess the sensitivity of the device in the current study and the ILRs proved to have a high rate of false positive misclassifications.

Conclusions: This study indicates that ILRs can be used for detection of PAF episodes and could be a useful ECG tool for horses presenting with poor performance. This methodology provides a platform to facilitate the long-term assessment of AF development and quantification of AF burden in horses. Further studies including both healthy and poor performing horses are needed in order to learn more about PAF prevalence in racehorses.
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http://dx.doi.org/10.1111/evj.13372DOI Listing
October 2020

Atrial fibrillation in horses part 1: Pathophysiology.

Vet J 2020 Sep 23;263:105521. Epub 2020 Jul 23.

Equine Cardioteam Gent University, Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Belgium.

Atrial fibrillation (AF) is the most common clinically relevant arrhythmia in horses, with a reported prevalence up to 2.5%. The pathophysiology has mainly been investigated in experimental animal models and human medicine, with limited studies in horses. Atrial fibrillation results from the interplay between electrical triggers and a susceptible substrate. Triggers consist of atrial premature depolarizations due to altered automaticity or triggered activity, or local (micro)reentry. The arrhythmia is promoted by atrial myocardial ion channel alterations, Ca handling alterations, structural abnormalities, and autonomic nervous system imbalance. Predisposing factors include structural heart disease such as valvular regurgitation resulting in chronic atrial stretch, although many horses show so-called 'lone AF' or idiopathic AF in which no underlying cardiac abnormalities can be detected using routine diagnostic techniques. These horses may have underlying ion channel dysfunction or undiagnosed myocardial (micro)structural alterations. Atrial fibrillation itself results in electrical, contractile and structural remodelling, fostering AF maintenance. Electrical remodelling leads to shortening of the atrial effective refractory period, promoting reentry. Contractile remodelling consists of decreased myocardial contractility, while structural remodelling includes the development of interstitial fibrosis and atrial enlargement. Reverse remodelling occurs after cardioversion to sinus rhythm, but full recovery may take weeks to months depending on duration of AF. The clinical signs of AF depend on the aerobic demands during exercise, ventricular rhythm response and presence of underlying cardiac disease. In horses with so-called 'lone AF', clinical signs are usually absent at rest but during exercise poor performance, exercise-induced pulmonary hemorrhage, respiratory distress, weakness or rarely collapse may develop.
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http://dx.doi.org/10.1016/j.tvjl.2020.105521DOI Listing
September 2020

Comparison of Tenocyte Populations from the Core and Periphery of Equine Tendons.

J Proteome Res 2020 10 2;19(10):4137-4144. Epub 2020 Sep 2.

Institute of Sports Medicine Copenhagen, Bispebjerg Hospital and Center for Healthy Aging, University of Copenhagen, 2400 Copenhagen, Denmark.

Tendon is a highly organized, dense connective tissue that has been demonstrated to have very little turnover. In spite of the low turnover, tendon can grow in response to loading, which may take place primarily at the periphery. Tendon injuries and recurrence of injuries are common in both humans and animals in sports. It is unclear why some areas of the tendon are more susceptible to such injuries and whether this is due to intrinsic regional differences in extracellular matrix (ECM) production or tissue turnover. This study aimed to compare populations of tenocytes derived from the tendon core and periphery. Tenocytes were isolated from equine superficial digital flexor tendons (SDFTs), and the proliferation capacity was determined. ECM production was characterized by immuno- and histological staining and by liquid chromatography-mass spectrometry-based proteomics. Core and periphery SDFT cultures exhibited comparable proliferation rates and had very similar proteome profiles, but showed biological variation in collagen type I deposition. In conclusion, the intrinsic properties of tenocytes from different regions of the tendon are very similar, and other factors in the tissue may contribute to how specific areas respond to loading or injury.
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http://dx.doi.org/10.1021/acs.jproteome.0c00591DOI Listing
October 2020

Detection of atrial fibrillation with implantable loop recorders in horses.

Equine Vet J 2021 Mar 28;53(2):397-403. Epub 2020 Jun 28.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Cardiac arrhythmias in horses are diagnosed by auscultation or electrocardiogram (ECG), which results in a low sensitivity for detecting arrhythmias that occur sporadically. Implantable loop recorders (ILRs) are small ECG devices placed subcutaneously, to automatically detect arrhythmias in human patients.

Objectives: To test ILRs ability to detect atrial fibrillation (AF) in horses. Furthermore, we hypothesised that anatomical location of the implant site might influence signal quality. Signal quality was evaluated both during exercise and over time.

Study Design: Experimental study.

Methods: In five Standardbred mares, eleven ILRs were implanted subcutaneously in up to three different positions (Front: pectoral region, Left-6: sixth left intercostal space and Ventral: xiphoid region) and AF induced. The R- and T-wave amplitudes were measured in all positions over time during AF. AF burden automatically registered by the ILRs over a 2-month period was compared with selected Holter ECG recordings.

Results: All three positions had stable R- and T-wave amplitudes during the study period and were of sufficient quality to allow AF detection at rest. The position Left-6 showed significantly higher R- and T-wave amplitudes compared with the other positions. During submaximal exercise only the Left-6 position was able to record ECG signals of diagnostic quality. No position yielded diagnostic signals at maximum exercise due to artefacts.

Main Limitations: Few horses and ILRs included and no spontaneous AF episodes were studied.

Conclusions: This preliminary study indicates that ILRs can be used for AF detection in horses, but the anatomical location is important for optimal ECG quality. Despite insufficient quality during exercise, ILRs were suitable for AF detection at rest. Therefore, the ILR may be a valuable diagnostic tool for detecting paroxysmal AF in horses.
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http://dx.doi.org/10.1111/evj.13301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891449PMC
March 2021

Effect of selective I inhibition by XAF-1407 in an equine model of tachypacing-induced persistent atrial fibrillation.

Br J Pharmacol 2020 08 24;177(16):3778-3794. Epub 2020 Jun 24.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.

Background And Purpose: Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, I may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific I inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF.

Experimental Approach: The pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction.

Key Results: XAF-1407 potently and selectively inhibited K 3.1/3.4 and K 3.4/3.4, underlying the I current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia.

Conclusion And Implications: XAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supports I inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.
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http://dx.doi.org/10.1111/bph.15100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393200PMC
August 2020

First catheter-based high-density endocardial 3D electroanatomical mapping of the right atrium in standing horses.

Equine Vet J 2021 Jan 14;53(1):186-193. Epub 2020 May 14.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Three-dimensional electroanatomical mapping is of potential interest in equine cardiology to identify arrhythmia mechanisms, characterise electroanatomical substrates and guide ablation strategies.

Objectives: To describe three-dimensional electroanatomical mapping in standing horses.

Study Design: Research methodology, proof of concept study.

Methods: Four Standardbred horses (2 geldings, 2 mares, median age 4.5 [4-9] years, mean bodyweight 485 [440-550] kg) were sedated and placed in stocks. Via the jugular vein, a high-density multipolar grid catheter (Advisor HD Grid Mapping Catheter with EnSite VelocityTM, Abbott Medical) was used for endocardial mapping of the right atrium. The P-wave on the surface ECG was used as a timing reference for simultaneous local activation time- and bipolar voltage-mapping. For a positional reference a 10-pole catheter (Abbott Medical) was placed in the caudal vena cava.

Results: Endocardial right atrial mapping guided by the three-dimensional mapping system and local electrograms was successfully performed in all four horses. A median of 32719 [25499-65078] points, covering the entire right atrium, were collected. Three-dimensional electroanatomical mapping provided detailed information about activation patterns and electrogram-characteristics of the sinoatrial node, intervenous tubercle and cavotricuspid isthmus. Additionally, transvenous biopsy forceps connected to the mapping system were visualised on screen to guide biopsy collection.

Main Limitations: The feasibility of electroanatomical mapping for the left atrium and in larger breeds requires further study.

Conclusions: High-density three-dimensional electroanatomical mapping of the right atrium is feasible in the standing horse.
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http://dx.doi.org/10.1111/evj.13265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818172PMC
January 2021

Pulmonary vein firing initiating atrial fibrillation in the horse: Oversized dimensions but similar mechanisms.

J Cardiovasc Electrophysiol 2020 05 5;31(5):1211-1212. Epub 2020 Mar 5.

Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia.

Atrial fibrillation is triggered by the pulmonary veins in humans. Although atrial fibrillation is known to occur in other species, the mechanisms of disease in these are not known. Here we present evidence for pulmonary vein triggers in the horse, where 3D HD Grid mapping was undertaken in the conscious state in the absence of fluoroscopy.
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http://dx.doi.org/10.1111/jce.14422DOI Listing
May 2020

Longitudinal study of electrical, functional and structural remodelling in an equine model of atrial fibrillation.

BMC Cardiovasc Disord 2019 10 21;19(1):228. Epub 2019 Oct 21.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Højbakkegaard Allé 5, 2630, Taastrup, Denmark.

Background: Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model.

Method: Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups.

Results: AFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed.

Conclusion: Horses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.
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http://dx.doi.org/10.1186/s12872-019-1210-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805623PMC
October 2019

Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation.

J Cardiovasc Electrophysiol 2019 04 28;30(4):596-606. Epub 2019 Jan 28.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.

Introduction: The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses.

Methods And Results: Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. Atrial fibrillatory activity was extracted from surface ECGs using spatiotemporal QRST cancellation. The mean atrial fibrillatory rate before drug infusion was 297 ± 27 fpm. Dofetilide reduced the atrial fibrillatory rate following the infusion of low doses (0.89 µg/kg, P < 0.05) and within 5 minutes preceding cardioversion (P < 0.05). Cardioversion with ranolazine was preceded by a reduction in the atrial fibrillatory rate in the last minute (P < 0.05). The combination of drugs reduced the atrial fibrillatory rate in a similar manner to dofetilide used alone. A trend toward a lower atrial fibrillatory rate before drug infusion was found among horses cardioverting on low doses of the drugs.

Conclusion: The atrial fibrillatory rate derived from surface ECGs showed a difference in the mode of action on AF between dofetilide and ranolazine. Dofetilide reduced the atrial fibrillatory rate, whereas ranolazine displayed a cardioverting mechanism that was distinct from a slowing of the fibrillatory process.
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http://dx.doi.org/10.1111/jce.13849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849868PMC
April 2019

Time-dependent antiarrhythmic effects of flecainide on induced atrial fibrillation in horses.

J Vet Intern Med 2018 Sep 22;32(5):1708-1717. Epub 2018 Aug 22.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.

Background: Pharmacological treatment of atrial fibrillation (AF) in horses can be challenging because of low efficacy and adverse effects. Flecainide has been tested with variable efficacy.

Objective: To test whether the efficacy of flecainide is dependent on AF duration.

Animals: Nine Standardbred mares.

Methods: Factorial study design. All horses were instrumented with a pacemaker and assigned to a control or an AF group. On day 0, all horses were in sinus rhythm and received 2 mg/kg flecainide IV. Atrial fibrillation subsequently was induced in the AF group by pacemaker stimulation. On days 3, 9, 27, and 55, flecainide was administered to all horses, regardless of heart rhythm.

Results: All horses in AF cardioverted to sinus rhythm on days 3 and 9. On day 27, 5/6 horses cardioverted, whereas only 2/6 cardioverted on day 55. The time from the start of flecainide infusion to cardioversion (range, 3-185 min, log transformed) showed linear correlation with the cumulative duration of AF (r  = .80, P < .0001). Flecainide induced abnormal QRS complexes in 4/6 AF horses and 1/3 controls. A positive correlation was found between heart rate before flecainide infusion and number of abnormal QRS complexes (0.14, P < .05). One horse suffered from cardiac arrest and died after flecainide infusion.

Conclusions And Clinical Importance: Flecainide is effective for cardioversion of short-term induced AF, but the effect decreases with AF duration. Controlling heart rate may minimize adverse effects caused by flecainide, but the drug should be used with great caution.
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http://dx.doi.org/10.1111/jvim.15287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189357PMC
September 2018

Effect of induced chronic atrial fibrillation on exercise performance in Standardbred trotters.

J Vet Intern Med 2018 Jul 10;32(4):1410-1419. Epub 2018 May 10.

Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Atrial fibrillation (AF) is the most common arrhythmia affecting performance in horses. However, no previous studies have quantified the performance reduction in horses suffering from AF.

Objectives: To quantify the effect of AF on maximum velocity (V ), maximum heart rate (HR ), heart rate recovery (T ), hematologic parameters and development of abnormal QRS complexes.

Animals: Nine Standardbred trotters.

Methods: Two-arm controlled trial. Six horses had AF induced by means of a pacemaker and 3 served as sham-operated controls. All horses were subjected to an exercise test to fatigue before (SET1) and after (SET2) 2 months of AF or sham. The V and HR were assessed using a linear mixed normal model. Abnormal QRS complexes were counted manually on surface ECGs.

Results: Atrial fibrillation resulted in a 1.56 m/sec decrease in V (P < .0001). In the AF group, HR  ± SD increased from 226 ± 11 bpm at SET1 to 311 ± 27 bpm at SET 2. The AF group had higher HR at SET2 compared with controls (P < .0001), whereas no difference between the control and AF groups was observed at SET1 (P = .96). Several episodes of wide complex tachycardia were observed during exercise in 3 of the AF horses during SET2.

Conclusions And Clinical Importance: Atrial fibrillation resulted in a significant reduction in performance, an increase in HR and development of abnormal QRS complexes during exercise, which may be a risk factor for collapse or sudden cardiac death.
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http://dx.doi.org/10.1111/jvim.15137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060327PMC
July 2018

Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation.

BMC Cardiovasc Disord 2017 Dec 8;17(1):289. Epub 2017 Dec 8.

Arrhythmia Clinic, Skåne University Hospital and Department of Cardiology, Clinical Sciences, Lund University, 21185, Lund, Sweden.

Background: Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim: The aim was to study characteristics of induced AF and its modification by flecainide.

Methods: The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results: At AF onset, AFR was 295 ± 52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269 ± 36 fpm in the control group (ns), and 364 ± 26 fpm in the horses with spontaneous persistent AF (P < 0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269 ± 36 fpm to a plateau of 313 ± 14 fpm before decreasing to 288 ± 28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P < 0.05).

Conclusion: AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.
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http://dx.doi.org/10.1186/s12872-017-0720-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723027PMC
December 2017

Antiarrhythmic Effects of Combining Dofetilide and Ranolazine in a Model of Acutely Induced Atrial Fibrillation in Horses.

J Cardiovasc Pharmacol 2018 01;71(1):26-35

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or noncardiac toxicity. Efficacy can be improved by combining 2 compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side effects. The purpose of this study was to investigate whether the effective doses of dofetilide and ranolazine can be reduced if the drugs are combined.

Methods: Dofetilide, ranolazine, and a combination of these were administered in 4 incremental dosing regimens to horses with acutely pacing-induced AF. Time to cardioversion, atrial effective refractory period, and AF vulnerability and duration were assessed.

Results: Of 8 horses, 6 cardioverted to sinus rhythm after infusion with a combination of 0.889 μg/kg dofetilide and 0.104 mg/kg ranolazine. Two horses cardioverted with 0.104 mg/kg ranolazine alone, and 3 cardioverted with 0.889 μg/kg dofetilide alone. The combination therapy decreased AF vulnerability (P < 0.05) and AF duration (P < 0.05). No change in atrial effective refractory period was detected with any of the drugs.

Conclusions: The combination of dofetilide and ranolazine showed increased antiarrhythmic effects on acutely induced AF in horses, affecting time to cardioversion, AF vulnerability, and AF duration.
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http://dx.doi.org/10.1097/FJC.0000000000000541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768216PMC
January 2018

Molecular cloning and functional expression of the K channel K7.1 and the regulatory subunit KCNE1 from equine myocardium.

Res Vet Sci 2017 Aug 11;113:79-86. Epub 2017 Sep 11.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Background: The voltage-gated K-channel K7.1 and the subunit KCNE1, encoded by the KCNQ1 and KCNE1 genes, respectively, are responsible for termination of the cardiac action potential. In humans, mutations in these genes can predispose patients to arrhythmias and sudden cardiac death (SCD).

Aim: To characterize equine K7.1/KCNE1 currents and compare them to human K7.1/KCNE1 currents to determine whether K7.1/KCNE1 plays a similar role in equine and human hearts.

Methods: mRNA encoding K7.1 and KCNE1 was isolated from equine hearts, sequenced, and cloned into expression vectors. The channel subunits were heterologously expressed in Xenopus laevis oocytes or CHO-K1 cells and characterized using voltage-clamp techniques.

Results: Equine K7.1/KCNE1 expressed in CHO-K1 cells exhibited electrophysiological properties that are overall similar to the human orthologs; however, a slower deactivation was found which could result in more open channels at fast rates.

Conclusion: The results suggest that the equine K7.1/KCNE1 channel may be important for cardiac repolarization and this could indicate that horses are susceptible to SCD caused by mutations in KCNQ1 and KCNE1.
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http://dx.doi.org/10.1016/j.rvsc.2017.09.010DOI Listing
August 2017

Appropriate threshold levels of cardiac beat-to-beat variation in semi-automatic analysis of equine ECG recordings.

BMC Vet Res 2016 Nov 28;12(1):266. Epub 2016 Nov 28.

Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Hoejbakkegaard Allé 5, 2630, Taastrup, Denmark.

Background: Although premature beats are a matter of concern in horses, the interpretation of equine ECG recordings is complicated by a lack of standardized analysis criteria and a limited knowledge of the normal beat-to-beat variation of equine cardiac rhythm. The purpose of this study was to determine the appropriate threshold levels of maximum acceptable deviation of RR intervals in equine ECG analysis, and to evaluate a novel two-step timing algorithm by quantifying the frequency of arrhythmias in a cohort of healthy adult endurance horses.

Results: Beat-to-beat variation differed considerably with heart rate (HR), and an adaptable model consisting of three different HR ranges with separate threshold levels of maximum acceptable RR deviation was consequently defined. For resting HRs <60 beats/min (bpm) the threshold level of RR deviation was set at 20%, for HRs in the intermediate range between 60 and 100 bpm the threshold was 10%, and for exercising HRs >100 bpm, the threshold level was 4%. Supraventricular premature beats represented the most prevalent arrhythmia category with varying frequencies in seven horses at rest (median 7, range 2-86) and six horses during exercise (median 2, range 1-24).

Conclusions: Beat-to-beat variation of equine cardiac rhythm varies according to HR, and threshold levels in equine ECG analysis should be adjusted accordingly. Standardization of the analysis criteria will enable comparisons of studies and follow-up examinations of patients. A small number of supraventricular premature beats appears to be a normal finding in endurance horses. Further studies are required to validate the findings and determine the clinical significance of premature beats in horses.
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http://dx.doi.org/10.1186/s12917-016-0894-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126988PMC
November 2016

Characterization and differentiation of equine experimental local and early systemic inflammation by expression responses of inflammation-related genes in peripheral blood leukocytes.

BMC Vet Res 2016 Jun 1;12:83. Epub 2016 Jun 1.

Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Background: Local inflammation may progress into systemic inflammation. To increase our understanding of the basic immunological processes during transition of equine local inflammation into a systemic state, investigation into the equine systemic immune response to local inflammation is warranted. Therefore, the aim of this study was to investigate the innate peripheral blood leukocyte (PBL) immune response to local inflammation in horses, and to compare this response with the PBL immune response during the early phase of acute systemic inflammation. Expression of 22 selected inflammation-related genes was measured in whole blood leukocytes from 6 horses in an experimental cross-over model of lipopolysaccharide- (LPS-) induced acute synovitis (3 μg LPS intraarticularly; locally inflamed [LI] horses) and endotoxemia (1 μg LPS/kg intravenously; systemically inflamed [SI] horses). Multiple clinical and hematological/biochemical examinations were performed, and serial blood samples were analyzed by reverse transcription quantitative real-time PCR. Post-induction expression profiles of all genes were compared between study groups using principal component analysis (PCA) and hierarchical clustering.

Results: Moderate synovitis and mild systemic inflammation of approximately 24 h duration was confirmed by clinical and paraclinical observations in LI and SI horses, respectively. In the LI group, samples obtained 3-16 h post-injection showed distinct clustering in the PCA compared with baseline levels, indicating a transcriptional response to local inflammation in PBLs in this time interval. There was no clinical or hematological indication of actual systemic inflammation. There was a clear separation of all LI samples from all SI samples in two distinct clusters, indicating that expression profiles in the two study groups were different, independent of time since LPS injection. Co-regulated genes formed four clusters across study groups which were distinctly differently regulated. Only few of individual genes displayed different expression between the study groups at all times after LPS injection.

Conclusions: Local inflammation in horses initiated an innate transcriptional response in PBLs, which differed from the transcriptional response during the early phase of systemic inflammation. This study may provide new insights into the immunobiology of PBLs during the transition of local inflammation into a systemic state.
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http://dx.doi.org/10.1186/s12917-016-0706-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888743PMC
June 2016

Pharmacological inhibition of IK1 by PA-6 in isolated rat hearts affects ventricular repolarization and refractoriness.

Physiol Rep 2016 Apr;4(8)

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

The inwardly rectifying potassium current (IK 1) conducted through Kir2.X channels contribute to repolarization of the cardiac action potential and to stabilization of the resting membrane potential in cardiomyocytes. Our aim was to investigate the effect of the recently discovered IK 1 inhibitor PA-6 on action potential repolarization and refractoriness in isolated rat hearts. Transiently transfected HEK-293 cells expressing IK 1 were voltage-clamped with ramp protocols. Langendorff-perfused heart experiments were performed on male Sprague-Dawley rats, effective refractory period, Wenckebach cycle length, and ventricular effective refractory period were determined following 200 nmol/L PA-6 perfusion. 200 nmol/L PA-6 resulted in a significant time-latency in drug effect on the IK 1 current expressed in HEK-293 cells, giving rise to a maximal effect at 20 min. In the Langendorff-perfused heart experiments, PA-6 prolonged the ventricular action potential duration at 90% repolarization (from 41.8 ± 6.5 msec to 72.6 ± 21.1 msec, 74% compared to baseline, P < 0.01, n = 6). In parallel, PA-6 significantly prolonged the ventricular effective refractory period compared to baseline (from 34.8 ± 4.6 msec to 58.1 ± 14.7 msec, 67%, P < 0.01, n = 6). PA-6 increased the short-term beat-to-beat variability and ventricular fibrillation was observed in two of six hearts. Neither atrial ERP nor duration of atrial fibrillation was altered following PA-6 application. The results show that pharmacological inhibition of cardiac IK 1 affects ventricular action potential repolarization and refractoriness and increases the risk of ventricular arrhythmia in isolated rat hearts.
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http://dx.doi.org/10.14814/phy2.12734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848716PMC
April 2016

Changes in heart rate, arrhythmia frequency, and cardiac biomarker values in horses during recovery after a long-distance endurance ride.

J Am Vet Med Assoc 2016 May;248(9):1034-42

OBJECTIVE To evaluate heart rate, heart rate variability, and arrhythmia frequency as well as changes in cardiac biomarker values and their association with heart rate in horses before and after an endurance ride. DESIGN Cross-sectional study. ANIMALS 28 Arabian horses competing in a 120- or 160-km endurance ride. PROCEDURES ECG recordings were obtained from each horse before (preride) and after (recovery) an endurance ride to evaluate changes in heart rate and the SD of normal R-R intervals (SDNN) during the initial 12 hours of recovery. Frequencies of supraventricular and ventricular premature complexes before and after the ride were evaluated. Blood samples were obtained before the ride and twice during recovery. Hematologic analyses included measurement of serum cardiac troponin I concentration and creatine kinase isoenzyme MB activity. RESULTS Heart rate was significantly increased and SDNN was decreased during the recovery versus preride period. Frequency of ventricular premature complexes increased during recovery, albeit not significantly, whereas frequency of supraventricular premature complexes was not significantly different between preride and recovery periods. Serum cardiac troponin I concentration and creatine kinase isoenzyme MB activity were significantly increased in the recovery versus preride period. No associations were identified between cardiac biomarkers and velocity, distance, or mean heart rate. CONCLUSIONS AND CLINICAL RELEVANCE Heart rate increased and SDNN decreased in horses after completion of an endurance ride. These and other cardiac changes suggested that prolonged exercise such as endurance riding might have cardiac effects in horses. Additional studies are needed to clarify the clinical relevance of the findings.
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http://dx.doi.org/10.2460/javma.248.9.1034DOI Listing
May 2016

Molecular Cloning and Functional Expression of the Equine K+ Channel KV11.1 (Ether à Go-Go-Related/KCNH2 Gene) and the Regulatory Subunit KCNE2 from Equine Myocardium.

PLoS One 2015 16;10(9):e0138320. Epub 2015 Sep 16.

Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.

The KCNH2 and KCNE2 genes encode the cardiac voltage-gated K+ channel KV11.1 and its auxiliary β subunit KCNE2. KV11.1 is critical for repolarization of the cardiac action potential. In humans, mutations or drug therapy affecting the KV11.1 channel are associated with prolongation of the QT intervals on the ECG and increased risk of ventricular tachyarrhythmia and sudden cardiac death--conditions known as congenital or acquired Long QT syndrome (LQTS), respectively. In horses, sudden, unexplained deaths are a well-known problem. We sequenced the cDNA of the KCNH2 and KCNE2 genes using RACE and conventional PCR on mRNA purified from equine myocardial tissue. Equine KV11.1 and KCNE2 cDNA had a high homology to human genes (93 and 88%, respectively). Equine and human KV11.1 and KV11.1/KCNE2 were expressed in Xenopus laevis oocytes and investigated by two-electrode voltage-clamp. Equine KV11.1 currents were larger compared to human KV11.1, and the voltage dependence of activation was shifted to more negative values with V1/2 = -14.2±1.1 mV and -17.3±0.7, respectively. The onset of inactivation was slower for equine KV11.1 compared to the human homolog. These differences in kinetics may account for the larger amplitude of the equine current. Furthermore, the equine KV11.1 channel was susceptible to pharmacological block with terfenadine. The physiological importance of KV11.1 was investigated in equine right ventricular wedge preparations. Terfenadine prolonged action potential duration and the effect was most pronounced at slow pacing. In conclusion, these findings indicate that horses could be disposed to both congenital and acquired LQTS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138320PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574097PMC
June 2016

Pharmacologic inhibition of small-conductance calcium-activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses.

Heart Rhythm 2015 Apr 24;12(4):825-35. Epub 2014 Dec 24.

Danish National Foundation Research Centre in Arrhythmias (DARC) and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Small-conductance calcium-activated potassium (SK) channels have been found to play an important role in atrial repolarization and atrial fibrillation (AF).

Objective: The purpose of this study was to investigate the existence and functional role of SK channels in the equine heart.

Methods: Cardiac biopsies were analyzed to investigate the expression level of the most prominent cardiac ion channels, with special focus on SK channels, in the equine heart. Subcellular distribution of SK isoform 2 (SK2) was assessed by immunohistochemistry and confocal microscopy. The electrophysiologic and anti-AF effects of the relative selective SK channel inhibitor NS8593 (5 mg/kg IV) were evaluated in anesthetized horses, focusing on the potential of NS8593 to terminate acute pacing-induced AF, drug-induced changes in atrial effective refractory period, AF duration and vulnerability, and ventricular depolarization and repolarization times.

Results: Analysis revealed equivalent mRNA transcript levels of the 3 SK channel isoforms in atria compared to ventricles. Immunohistochemistry and confocal microscopy displayed a widespread distribution of SK2 in both atrial and ventricular cardiomyocytes. NS8593 terminated all induced AF episodes (duration ≥15 minutes), caused pronounced prolongation of atrial effective refractory period, and reduced AF duration and vulnerability. QRS duration and QTc interval were not affected by treatment.

Conclusion: SK channels are widely distributed in atrial and ventricular cardiomyocytes and contribute to atrial repolarization. Inhibition by NS8593 terminates pacing-induced AF of short duration and decreases AF duration and vulnerability without affecting ventricular conduction and repolarization. Thus, inhibition by NS8593 demonstrates clear atrial antiarrhythmic properties in healthy horses.
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http://dx.doi.org/10.1016/j.hrthm.2014.12.028DOI Listing
April 2015

Diurnal modulation and sources of variation affecting ventricular repolarization in Warmblood horses.

J Vet Cardiol 2014 Dec 27;16(4):265-76. Epub 2014 Jul 27.

Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 100, 1870 Frederiksberg C, Denmark.

Objectives: Irregularities in cardiac repolarization are known to predispose for arrhythmias and sudden cardiac death in humans. The QT interval is a quantitative measurement of repolarization, and clinically, the QTc (QT interval corrected for heart rate) and Tpeak to Tend intervals (TpTe) are used as repolarization markers. To support the use of these markers in horses, we sought to describe the possible influence of the environment, time of day, day-to-day effects, T wave conformation, age, body weight (BW), and horse-to-horse variation on repolarization measurements.

Animals: 12 Warmblood geldings, age 10.8 ± 4.8 years.

Methods: Holter ECGs were performed on days 0, 7 and 14. Measures of RR, QT, QTp, QTc and TpTe intervals and T wave conformation were obtained each hour during the recordings. An ANCOVA analysis was performed to estimate diurnal variation and the sources of variation affecting these intervals.

Results: Differences between individual horses were the largest source of repolarization variability although the environment had a significant effect on repolarization as well. Diurnal variation affected both the RR interval and the repolarization markers. The QT, QTc and TpTe intervals were prolonged on day 0. Biphasic T waves shortened the TpTe interval approximately 10 ms. Age and BW did not appear to affect repolarization.

Conclusions: Equine repolarization markers exhibit significant variation. Factors affecting repolarization measurements include horse-to-horse variation, diurnal variation, the environment, and T wave conformation. These factors must be considered if markers of equine repolarization are used diagnostically.
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http://dx.doi.org/10.1016/j.jvc.2014.07.001DOI Listing
December 2014

Cardiac arrhythmias and electrolyte disturbances in colic horses.

Acta Vet Scand 2014 Oct 2;56(1):58. Epub 2014 Oct 2.

Background: Despite increased focus on cardiac arrhythmias in horses, the nature and prevalence is still poorly described. Case reports suggest that arrhythmias occurring secondary to systemic disease are seen more commonly in the clinic than arrhythmias caused by cardiac disease. The aim of this study was to investigate the prevalence of arrhythmias in colic horses referred for hospital treatment. Associations between electrolyte disturbances and arrhythmias were also investigated.

Results: Heart rate was 37.4 ± 3.7 bpm in the control group, and 51.6 ± 11.8 bpm, in the colic group, which was significantly different (P < 0.0001). AV blocks and SVPCs were found in both groups, however only colic horses showed VPCs. No significant difference between the two groups was found for AV blocks, SVPCs, and VPCs (P = 0.08 - 0.76). The mean levels of potassium, sodium, ionized calcium, and chloride were significantly lower in the colic group compared to the control group at admission. Mean levels of glucose and L-lactate were significantly elevated in the colic group (P < 0.05).

Conclusions: This study describes prevalence of cardiac arrhythmias and electrolytes concentrations in colic horses compared to healthy controls. Although we only observed VPCs in the colic horses, no significant differences between colic horses and controls were found. Despite the colic horses having electrolyte changes at admission no correlation was found between the electrolyte disturbances and cardiac arrhythmias. Although no clear conclusions can be drawn from the present study, the results indicate that relatively mild colic per se is not pro-arrhythmogenic, whereas severe colic probably are more likely to result in ventricular arrhythmia.
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http://dx.doi.org/10.1186/s13028-014-0058-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189753PMC
October 2014