RESUMEN
The long QT syndrome (LQTS) is a channelopathy that can lead to severe arrhythmia and sudden cardiac death. Pharmacologically induced LQTS is caused by interaction between drugs and potassium channels, especially the Kv 11.1 channel. Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine. However, some compounds, such as trimethoprim-sulfonamide combinations are still widely used in veterinarian medicine. Therefore, we investigate the effect of trimethoprim-sulfadiazine (TMS), trimethoprim, sulfadiazine, and detomidine on equine-specific Kv 11.1 channels. Kv 11.1 channels cloned from equine hearts were heterologously expressed in Xenopus laevis oocytes, and whole cell currents were measured by two-electrode voltage-clamp before and after drug application. TMS blocked equine Kv 11.1 current with an IC50 of 3.74 mm (95% CI: 2.95-4.73 mm) and affected the kinetics of activation and inactivation. Similar was found for trimethoprim but not for sulfadiazine, suggesting the effect is due to trimethoprim. Detomidine did not affect equine Kv 11.1 current. Thus, equine Kv 11.1 channels are also susceptible to pharmacological block, indicating that some drugs may have the potential to affect repolarization in horse. However, in vivo studies are needed to assess the potential risk of these drugs to induce equine LQTS.
Asunto(s)
Canal de Potasio ERG1/efectos de los fármacos , Imidazoles/farmacología , Sulfadoxina/farmacología , Trimetoprim/farmacología , Animales , Combinación de Medicamentos , Electrodos , Electrofisiología , Caballos , Imidazoles/efectos adversos , Oocitos/efectos de los fármacos , Oocitos/fisiología , Técnicas de Placa-Clamp/veterinaria , Sulfadoxina/efectos adversos , Trimetoprim/efectos adversos , Xenopus laevisRESUMEN
OBJECTIVES: Quantitative measurements of cardiac repolarization, defined as the electrocardiographic QT interval, have important diagnostic implications in humans, as irregularities can trigger potentially fatal ventricular tachyarrhythmia. In both humans and horses, cardiac repolarization is influenced to some extent by heart rate, age, body weight (BW), sex, autonomic tone, and environment. In horses, there is substantial inter-breed variation in size and training, and the aims of this study were therefore to determine the best model describing the QT to RR relationship in breeds of various athletic horses and to test for differences in the QT interval. ANIMALS: Ten Icelandic horses, 10 Arabian horses, 10 Thoroughbreds, 10 Standardbreds, six Coldblood trotters, 10 Warmbloods (dressage) and 10 Warmbloods (show jumping). All horses were geldings. METHODS: QT intervals were measured from resting to peak exercise level and plotted against RR intervals. Data points were fitted with relevant regression models, and the effect of breed, BW, and estimated exercise intensity was examined. RESULTS: For all breeds in this study, the QT interval was best described as a function of RR by the piecewise linear regression model. The breed of horse had a significant effect on the model. There was no systematic effect of BW or estimated exercise intensity, but a high inter-horse variability was observed. CONCLUSIONS: The equine QT interval should preferably be corrected for heart rate according to breed. In addition, the results indicate that equine studies of the QT interval must be designed to eliminate the influence of a large inter-horse variation.
Asunto(s)
Electrocardiografía/veterinaria , Corazón/fisiología , Caballos/fisiología , Esfuerzo Físico/fisiología , Descanso/fisiología , Animales , Femenino , Frecuencia Cardíaca , Masculino , Especificidad de la EspecieRESUMEN
The authors describe a group project in a graduate nursing course in which the students developed a consumer satisfaction survey tool for use in an academic nursing center. Included in this article are a description of the project inception, course objectives, group collaboration, review of the literature, and tool development. The completed tool and recommendations are included.