Publication: Efecto de la dronedarona sobre la regresión de la hipertrofia ventricular. Estudio experimental en un modelo de rata hipertensa
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2018-04-04
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Universidad Complutense de Madrid
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Abstract
La hipertensión arterial (HTA) es la principal causa de la arritmia sostenida más frecuente en la práctica clínica, la fibrilación auricular (FA). El tratamiento antihipertensivo tiene la capacidad de normalizar los niveles de tensión arterial, de reducir el daño cardíaco causado por la HTA y prevenir la aparición de la FA. El objetivo de nuestro trabajo es analizar si la dronedarona, uno de los fármacos antiarrítmicos con una gama de efectos más amplia, también tiene capacidad para modificar las alteraciones estructurales cardíacas causadas por la HTA. Este efecto sería muy interesante, ya que la modificación del sustrato podría ser un mecanismo facilitador para el efecto antiarrítmico de la dronedarona en el tratamiento de la FA. Material y métodos. Para evaluar el efecto de la dronedarona sobre el remodelado cardíaco inducido por la HTA desarrollamos un estudio en el modelo experimental formado por las ratas genéticamente hipertensas SHR y su control normotenso WKY, uno de los modelos más ampliamente utilizados en la investigación básica de los mecanismos implicados en la HTA esencial.Las ratas SHR se dividieron de forma aleatoria en dos grupos, un grupo de intervención (SHR-D, n=9) que recibió tratamiento con dronedarona durante un periodo de 14 días y un grupo de control (SHR-C, n=9) que recibió placebo. Se añadió un tercer grupo de ratas control normotensas (WKY, n=9). Tras finalizar el ciclo de tratamiento con dronedarona, estudiamos en los animales 1) la anatomía y función cardíaca con ecocardiograma transtorácico 2) el metabolismo cardíaco a través de un estudio con PET/CT del metabolismo cardíaco de la glucosa y 3) la estructura del miocardio por medio del análisis histológico del tamaño de los miocitos y de la cantidad de contenido en colágeno...
Arterial hypertension (AH) is the main cause for the most frequent sustained arrhythmia in clinical practice, atrial fibrillation (AF). Antihypertensive treatment has the potential to restore blood pressure levels, reduce the cardiac damage caused by AH and prevent the development of AF. The objective of the present work is to study if dronedarone, one of the antiarrhythmic drugs with a wider range of effects, has also the potential to modify the cardiac alterations caused by AH. This effect should be very interesting in clinical practice, because substrate modification could potentiate the antiarrhythmic effect of dronedarone in AF treatment. Material and methods. To evaluate the effect of dronedarone on cardiac remodeling caused by AF, we designed a study using the classical experimental model composed of the spontaneously hypertensive rats SHR and their normotensive control rats WKY, one of the most frequently used models in research of basic mechanisms involved in essential AH. SHR rats were randomly assigned to an intervention group (SHR-D, n=9), where animals received dronedarone treatment for a period of 14 days, or to a control group (SHR-C, n=9) where rats were given placebo. A third group with normotensive WKY control rats (WKY, n=9) was also added. At the end of the treatment with dronedarone we studied in all the rats the 1) cardiac anatomy and function using transthoracic echocardiogram 2) cardiac metabolism using the PET/CT study of the glucose metabolism and 3) cardiac structure by histological analysis of myocyte size and collagen content...
Arterial hypertension (AH) is the main cause for the most frequent sustained arrhythmia in clinical practice, atrial fibrillation (AF). Antihypertensive treatment has the potential to restore blood pressure levels, reduce the cardiac damage caused by AH and prevent the development of AF. The objective of the present work is to study if dronedarone, one of the antiarrhythmic drugs with a wider range of effects, has also the potential to modify the cardiac alterations caused by AH. This effect should be very interesting in clinical practice, because substrate modification could potentiate the antiarrhythmic effect of dronedarone in AF treatment. Material and methods. To evaluate the effect of dronedarone on cardiac remodeling caused by AF, we designed a study using the classical experimental model composed of the spontaneously hypertensive rats SHR and their normotensive control rats WKY, one of the most frequently used models in research of basic mechanisms involved in essential AH. SHR rats were randomly assigned to an intervention group (SHR-D, n=9), where animals received dronedarone treatment for a period of 14 days, or to a control group (SHR-C, n=9) where rats were given placebo. A third group with normotensive WKY control rats (WKY, n=9) was also added. At the end of the treatment with dronedarone we studied in all the rats the 1) cardiac anatomy and function using transthoracic echocardiogram 2) cardiac metabolism using the PET/CT study of the glucose metabolism and 3) cardiac structure by histological analysis of myocyte size and collagen content...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Cirugía, leída el 21/06/2017