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Physical activity can activate extracellular matrix (ECM) protein synthesis and influence the size and mechanical properties of tendon. In this study, we aimed to investigate whether different training histories of horses would influence the synthesis of collagen and other matrix proteins and alter the mechanical properties of tendon. Samples from superficial digital flexor tendon (SDFT) from horses that were either (a) currently race trained (n = 5), (b) previously race trained (n = 5) or (c) untrained (n = 4) were analysed for matrix protein abundance (mass spectrometry), collagen and glycosaminoglycan (GAG) content, ECM gene expression and mechanical properties. It was found that ECM synthesis by tendon fibroblasts in vitro varied depending upon the previous training history. In contrast, fascicle morphology, collagen and GAG content, mechanical properties and ECM gene expression of the tendon did not reveal any significant differences between groups. In conclusion, although we could not identify any direct impact of the physical training history on the mechanical properties or major ECM components of the tendon, it is evident that horse tendon cells are responsive to loading in vivo, and the training background may lead to a modification in the composition of newly synthesised matrix.
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[Figure: see text].
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Potenciales de Acción , Bloqueo Atrioventricular/metabolismo , Nodo Atrioventricular/metabolismo , Canales de Calcio Tipo L/metabolismo , Frecuencia Cardíaca , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Miocitos Cardíacos/metabolismo , Resistencia Física , Animales , Bloqueo Atrioventricular/inducido químicamente , Bloqueo Atrioventricular/diagnóstico , Bloqueo Atrioventricular/fisiopatología , Nodo Atrioventricular/fisiopatología , Atropina , Biopsia , Canales de Calcio Tipo L/genética , Modelos Animales de Enfermedad , Electrocardiografía , Caballos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Condicionamiento Físico Animal , Propranolol , Natación , Transcripción GenéticaRESUMEN
The myotendinous junction (MTJ) is a specialized interface for transmitting high forces between the muscle and tendon and yet the MTJ is a common site of strain injury with a high recurrence rate. The aim of this study was to identify previously unknown MTJ components in mature animals and humans. Samples were obtained from the superficial digital flexor (SDF) muscle-tendon interface of 20 horses, and the tissue was separated through a sequential cryosectioning approach into muscle, MTJ (muscle tissue enriched in myofiber tips attached to the tendon), and tendon fractions. RT-PCR was performed for genes known to be expressed in the three tissue fractions and t-distributed stochastic neighbor embedding (t-SNE) plots were used to select the muscle, MTJ, and tendon samples from five horses for RNA sequencing. The expression of previously known and unknown genes identified through RNA sequencing was studied by immunofluorescence on human hamstring MTJ tissue. The main finding was that RNA sequencing identified the expression of a panel of 61 genes enriched at the MTJ. Of these, 48 genes were novel for the MTJ and 13 genes had been reported to be associated with the MTJ in earlier studies. The expression of known [COL22A1 (collagen XXII), NCAM (neural cell adhesion molecule), POSTN (periostin), NES (nestin), OSTN (musclin/osteocrin)] and previously undescribed [MNS1 (meiosis-specific nuclear structural protein 1), and LCT (lactase)] MTJ genes was confirmed at the protein level by immunofluorescence on tissue sections of human MTJ. In conclusion, in muscle-tendon interface tissue enriched with myofiber tips, we identified the expression of previously unknown MTJ genes representing diverse biological processes, which may be important in the maintenance of the specialized MTJ.
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Músculos Isquiosurales/metabolismo , Tendones Isquiotibiales/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , ARN Mensajero/genética , Adulto , Animales , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Colágeno/genética , Colágeno/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ontología de Genes , Caballos , Humanos , Masculino , Anotación de Secuencia Molecular , Proteínas Musculares/clasificación , Proteínas Musculares/metabolismo , Nestina/genética , Nestina/metabolismo , Moléculas de Adhesión de Célula Nerviosa/genética , Moléculas de Adhesión de Célula Nerviosa/metabolismo , ARN Mensajero/clasificación , ARN Mensajero/metabolismo , Análisis de Secuencia de ARN , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
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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Traumatismos de los Tendones , Tenocitos , Animales , Matriz Extracelular , Caballos , Humanos , Proteómica , TendonesRESUMEN
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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Fibrilación Atrial/veterinaria , Enfermedades de los Caballos/fisiopatología , Venas Pulmonares/fisiopatología , Potenciales de Acción , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Sedación Consciente/veterinaria , Electrocardiografía/veterinaria , Técnicas Electrofisiológicas Cardíacas/veterinaria , Frecuencia Cardíaca , Enfermedades de los Caballos/diagnóstico , Caballos , Masculino , Posición de PieRESUMEN
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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Antiarrítmicos/farmacología , Fibrilación Atrial/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Fenetilaminas/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Ranolazina/farmacología , Bloqueadores de los Canales de Sodio/farmacología , Sulfonamidas/farmacología , Potenciales de Acción , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Electrocardiografía , Femenino , Caballos , Masculino , Factores de TiempoRESUMEN
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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Potenciales de Acción , Fibrilación Atrial/fisiopatología , Función del Atrio Izquierdo , Remodelación Atrial , Atrios Cardíacos/fisiopatología , Frecuencia Cardíaca , Potenciales de Acción/efectos de los fármacos , Animales , Antiarrítmicos/farmacología , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/etiología , Fibrilación Atrial/metabolismo , Función del Atrio Izquierdo/efectos de los fármacos , Remodelación Atrial/efectos de los fármacos , Estimulación Cardíaca Artificial , Modelos Animales de Enfermedad , Femenino , Fibrosis , Flecainida/farmacología , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Caballos , Canales Iónicos/metabolismo , Factores de TiempoRESUMEN
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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Antiarrítmicos/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Fenetilaminas/administración & dosificación , Ranolazina/administración & dosificación , Sulfonamidas/administración & dosificación , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Modelos Animales de Enfermedad , Combinación de Medicamentos , Femenino , Caballos , Infusiones Intravenosas , MasculinoRESUMEN
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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Antiarrítmicos/farmacología , Fibrilación Atrial/prevención & control , Flecainida/farmacología , Atrios Cardíacos/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Estimulación Cardíaca Artificial , Modelos Animales de Enfermedad , Electrocardiografía , Femenino , Atrios Cardíacos/fisiopatología , Caballos , Masculino , Factores de TiempoRESUMEN
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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Inflamación/veterinaria , Leucocitos/inmunología , Sinovitis/veterinaria , Animales , Estudios Cruzados , Femenino , Perfilación de la Expresión Génica , Caballos , Inmunidad Innata , Inflamación/genética , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Masculino , Sinovitis/inducido químicamente , Sinovitis/inmunologíaRESUMEN
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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Electrocardiografía/veterinaria , Caballos/fisiología , Animales , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/veterinaria , Femenino , Frecuencia Cardíaca , Masculino , Valores de ReferenciaRESUMEN
BACKGROUND: Atrial fibrillation (AF) has been proposed as a risk factor for exercise-induced pulmonary haemorrhage (EIPH) due to increased pressure in the left atrium. OBJECTIVE: To evaluate if AF was associated with EIPH following a standardised exercise test (SET) to fatigue. STUDY DESIGN: Two-arm controlled experiment. METHODS: Ten untrained Standardbred mares mean (standard deviation [SD]) age 6 (2) years performed a SET on the treadmill in sinus rhythm (SR) (SET1) and 25-44 days after induction of self-sustained AF (SET2). AF was induced by tachypacing using a pacing device. Endoscopy, including tracheal wash and bronchoalveolar lavage (BAL), was performed 48-72 h before and 24 h after the two SETs. In addition, endoscopic grading of tracheal blood was performed 2 h after each SET. RESULTS: After SET1, none of the horses showed blood in the trachea, and two horses showed erythrophagocytosis. Following SET2, two horses had grade 1 blood in the trachea and free erythrocytes and erythrophagocytosis in the BAL, while another two horses had erythrophagocytosis in the BAL. In SET2, the overall performance on the treadmill was decreased with a lower maximum velocity (SET1 10.3 ± 0.8 m/s vs. SET2 8.9 ± 0.9 m/s, p = 0.004), a higher heart rate (284 ± 21 vs. 221 ± 18 bpm, p = 0.003) and more abnormal QRS complexes (p < 0.001) compared with SET1. CONCLUSIONS: Two horses showed signs of EIPH, resulting in visible blood in the trachea, when exercising in AF compared with SR. However, a possible link between EIPH, pulmonary pressure and AF needs to be further elucidated.
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Fibrilación Atrial , Enfermedades de los Caballos , Enfermedades Pulmonares , Condicionamiento Físico Animal , Animales , Caballos , Femenino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/veterinaria , Prueba de Esfuerzo/veterinaria , Prueba de Esfuerzo/efectos adversos , Líquido del Lavado Bronquioalveolar , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/veterinaria , Hemorragia/etiología , Hemorragia/veterinaria , Condicionamiento Físico Animal/efectos adversos , Factores de Riesgo , Enfermedades de los Caballos/etiologíaRESUMEN
BACKGROUND: Paroxysmal atrial fibrillation (pAF) occurs sporadically and can impair athletic performance. Gold standard for diagnosis is surface electrocardiography (ECG), however, this requires AF to be sustained. Implantable loop recorders (ILRs) are routinely used for AF detection in human medicine. While ILR placement has been studied in horses, its AF detection performance is unknown. OBJECTIVES: (I) Validation of ILRs for AF detection in horses. (II) Determining pAF incidence using ILRs and estimate the positive predictive value (PPV). STUDY DESIGN: (I) Experimental study; (II) Longitudinal observational study. METHODS: (I) Implantation of ILRs in 15 horses with AF and 13 horses in sinus rhythm. Holter ECGs were recorded at: 1, 4, 8, 12 and 16 weeks of AF. The ILR ECGs were compared with surface ECGs to assess diagnostic sensitivity and specificity. (II) Eighty horses (43 Warmbloods, 37 Standardbreds) with ILRs were monitored for 367 days [IQR 208-621]. RESULTS: (I) ILRs detected AF on all recording days, in horses with AF, with a sensitivity of 66.1% (95% CI: 65.8-66.5) and a specificity of 99.99% (95% CI: 99.97-99.99). The sensitivity remained consistent across all time points. (II) The incidence of pAF was 6.3% (5/80). In horses with pAF, the PPV ranged from 8% to 87%. Increased body condition score (BCS > 6/9) was associated with an increased number of false positive episodes (p = 0.005). MAIN LIMITATIONS: (I) Horses were stabled during the ECG recordings, and AF was induced, rather than naturally occurring pAF. (II) Integrated algorithm in this ILR is optimised for AF detection in humans using remote monitors. Additionally, sensing is affected by motion artefacts. CONCLUSION: The ILR reliably detected AF in resting horses, particularly in horses with normal BCS (6/9). The ILR proved useful to detect pAF and is recommended alongside Holter monitoring for diagnostic workup of horses with suspected pAF.
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Background: Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone. Aim: To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M2) and the G protein-gated inwardly rectifying K+ (GIRK4) channel that mediates the cardiac IK,ACh current. Method: Eighteen horses with a low burden of second-degree AV block (median 8 block per 20â h, IQR: 32 per 20â h) were assigned to the control group, while 17 horses with a high burden of second-degree AV block (median: 408 block per 20â h, IQR: 1,436 per 20â h) were assigned to the AV block group. Radiotelemetry ECG recordings were performed to assess PR interval and incidence of second-degree AV block episodes at baseline and on pharmacological blockade of the autonomic nervous system (ANS). Wenckebach cycle length was measured by intracardiac pacing (n = 16). Furthermore, the expression levels of the M2 receptor and the GIRK4 subunit of the IKACh channel were quantified in biopsies from the right atrium, the AV node and right ventricle using immunohistochemistry and machine learning-based automated segmentation analysis (n = 9 + 9). Results: The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05â s; p < 0.001) and a longer Wenckebach cycle length (mean ± SD, 995 ± 86â ms; p = 0.007) at baseline. After blocking the ANS, all second-degree AV block episodes were abolished, and the difference in PR interval disappered (p = 0.80). The AV block group had significantly higher expression of the M2 receptor (p = 0.02), but not the GIRK4 (p = 0.25) in the AV node compared to the control group. Both M2 and GIRK4 were highly expressed in the AV node and less expressed in the atria and the ventricles. Conclusion: Here, we demonstrate the involvement of the m2R-IK,ACh pathway in underlying second-degree AV block in horses. The high expression level of the M2 receptor may be responsible for the high burden of second-degree AV blocks seen in some horses.
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Atrial fibrillation (AF) is more prevalent in athletes, and currently, the mechanisms are not fully understood. Atrial fibrillation inducibility and stability was investigated in trained and untrained Standardbred racehorses. The horses underwent echocardiography for evaluation of atrial size. High-density mapping during AF was performed, and the presence of structural remodeling, as well as the expression of inflammatory and pro-inflammatory markers in the atria, was studied. Atrial fibrillation sustained significantly longer after tachypacing in the trained horses, whereas no difference in AF inducibility was found. The untrained horses displayed a significant difference in the AF complexity when comparing right and left atria, whereas such difference was not observed in the trained animals. No evidence of increased structural remodeling or inflammation could be identified. Left atrial dimensions were not significantly increased. The increased AF sustainability in trained horses was not related to fibrosis or inflammation as seen in other animal exercise models.
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Fibrilación Atrial , Humanos , Caballos , Animales , Atrios Cardíacos , Ecocardiografía , InflamaciónRESUMEN
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, dog 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 focuses on anti-arrhythmic investigations in large animals. Initially, spontaneous AF in small and large mammals is 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 anti-arrhythmic compounds either frequently used in the human clinic (ranolazine, flecainide, vernakalant and amiodarone) or being promising new AF medicine candidates (IK,Ach , ISK,Ca and IK2P blockers). LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.
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Antiarrítmicos , Fibrilación Atrial , Animales , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Perros , Flecainida/farmacología , Caballos , Mamíferos , Modelos Animales , Ranolazina , PorcinosRESUMEN
Atrial fibrillation (AF) is the most common arrhythmia in horses causing poor performance. As in humans, the condition can be intermittent in nature, known as paroxysmal atrial fibrillation (pAF). This review covers the literature relating to pAF in horses and includes references to the human literature to compare pathophysiology, clinical presentation, diagnostic tools and treatment. The arrhythmia is diagnosed by auscultation and electrocardiography (ECG), and clinical signs can vary from sudden loss of racing performance to reduced fitness or no signs at all. If left untreated, pAF may promote electrical, functional and structural remodeling of the myocardium, thus creating a substrate that is able to maintain the arrhythmia, which over time may progress into permanent AF. Long-term ECG monitoring is essential for diagnosing the condition and fully understanding the duration and frequency of pAF episodes. The potential to adapt human cardiac monitoring systems and computational ECG analysis is therefore of interest and may benefit future diagnostic tools in equine medicine.
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Second-degree atrioventricular (AV) block is the most common cardiac arrhythmia in horses, affecting 40-90% depending on breed. Usually, the AV blocks occur while the horses are resting and disappear upon exercise and are, therefore, considered to be uneventful for horses. However, if the AV blocks occur frequently, this may result in syncope and collapse. Identifying the cause of second-degree AV block is difficult and often subscribed to high vagal tone. In this report, we present an eight-year-old Quarter horse with a high burden of second-degree AV blocks and multiple collapses. The clinical examination, including neurological examination, blood analysis, 24-h ECG recording and cardiac echocardiography, did not reveal any signs of general or cardiovascular disease besides a high burden of second-degree AV blocks (~300 blocks per hour) and a hyperechoic area in the AV nodal region. An implantable loop recorder (ILR) was inserted to monitor the cardiac rhythm. The ILR detected several consecutive second-degree AV blocks and pauses above 5 s. However, unfortunately, no recordings were available during the collapses. Eventually, the horse was euthanized and the heart inspected. The aortic root was severely cartilaginous and appeared to penetrate the AV node, especially in the His bundle region, possibly explaining the hampered AV conduction. Nevertheless, it is still uncertain if the AV nodal disruption caused the collapses and more knowledge on AV nodal diseases in horses is warranted.
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During acute myocardial infarction (AMI), the ischemia and necrosis of the infarcted tissue result in local electrophysiological changes, which bring about deviations of the ST segment and T wave. In this case report, the aim was to investigate whether these changes could be detected with a 12-lead electrocardiogram (ECG) during acute occlusion of the coronary artery in a 15-year-old Standardbred mare (scheduled for euthanasia due to non-cardiac health problems). The left anterior descending (LAD) coronary artery was occluded using an angioplasty balloon catheter guided through the carotid artery. Two coronary occlusions of 30 min were induced, separated by a 10-min reperfusion phase. AMI led to ST deviations and T-wave amplitude changes (maximum ST deviation was 1.98 mV; T-wave amplitude increased from 6.58 to 9.25 mV). The ST segment almost returned to the baseline during the reperfusion phase. The ECG changes seen after the infarction were comparable to those reported in other species with AMI, suggesting that the 12-lead-ECG can potentially be used to detect signs of myocardial infarction in horses.
RESUMEN
BACKGROUND: Long-term exercise induces cardiac remodeling that potentially influences the electrical properties of the heart. HYPOTHESIS/OBJECTIVES: We assessed whether training alters cardiac conduction in Standardbred racehorses. ANIMALS: Two hundred one trained and 52 untrained Standardbred horses. METHODS: Cross-sectional study. Resting ECG recordings were analyzed to assess heart rate (HR) along with standard ECG parameters and for identification of atrial and ventricular arrhythmias. An electrophysiological study was performed in 13 horses assessing the effect of training on sinoatrial (SA) and atrioventricular (AV) nodal function by sinus node recovery time (SNRT) and His signal recordings. Age and sex adjustments were implemented in multiple and logistic regression models for comparison. RESULTS: Resting HR in beats per minute (bpm) was lower in trained vs untrained horses (mean, 30.8 ± 2.6 bpm vs 32.9 ± 4.2 bpm; P = .001). Trained horses more often displayed second-degree atrioventricular block (2AVB; odds ratio, 2.59; P = .04). No difference in SNRT was found between groups (n = 13). Mean P-A, A-H, and H-V intervals were 71 ± 20, 209 ± 41, and 134 ± 41 ms, respectively (n = 7). We did not detect a training effect on AV-nodal conduction intervals. His signals were present in 1 horse during 2AVB with varying H-V interval preceding a blocked beat. CONCLUSIONS AND CLINICAL IMPORTANCE: We identified decreased HR and increased frequency of 2AVB in trained horses. In 5 of 7 horses, His signal recordings had variable H-V intervals within each individual horse, providing novel insight into AV conduction in horses.