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La repolarización ventricular heterogénea proporciona un sustrato para las arritmias en un modelo de pastor alemán de
Maria N Obreztchikova1, Eugene A Sosunov, Evgeny P Anyukhovsky
1Department of Pharmacology and Pediatrics, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Circulation
|August 27, 2003
Resumen
La repolarización ventricular izquierda heterogénea en perros pastores alemanes crea un sustrato aritmogénico para la muerte súbita. Las diferencias espaciales en las corrientes repolarizantes (IKr e IKs) y su respuesta a las catecolaminas contribuyen a este riesgo.
Área de la Ciencia:
- Cardiología Cardiología.
- Biología Molecular Biología Molecular
- Medicina Veterinaria La medicina veterinaria es el campo de la medicina en el que se desarrolla la medicina veterinaria.
Sus antecedentes:
- Los perros pastores alemanes con arritmias hereditarias sirven como modelo para las taquicardias ventriculares humanas dependientes de catecolaminas.
- Investigar el papel de la heterogeneidad de la repolarización ventricular izquierda en la taquicardia ventricular dependiente de la pausa es crucial.
Objetivo del estudio:
- Para probar la hipótesis de que la heterogeneidad de la repolarización ventricular izquierda crea un sustrato aritmogénico en perros pastores alemanes.
- Para entender la base molecular de esta heterogeneidad mediante el examen de las corrientes repolarizantes.
Principales métodos:
- Técnicas de microelectrodos para registrar potenciales de acción (PA) de diferentes regiones de la pared ventricular izquierda (VV).
- Clamp de tensión de célula completa para estudiar las corrientes repolarizantes (IKr e IKs) en miocitos LV aislados.
- Administración de isoproterenol para evaluar la respuesta a las catecolaminas.
Principales resultados:
- Los perros afectados mostraron una heterogeneidad significativa de la duración del potencial de acción de LV (APD), a diferencia de los perros no afectados.
- El isoproterenol afectó diferencialmente la APD en perros afectados, acortándola anterobasalmente y prolongándola anteroseptalmente.
- Los perros afectados mostraron un IKr anterobasal reducido y una activación de IKs alterada en comparación con los perros no afectados.
Conclusiones:
- La heterogeneidad espacial en la expresión de IKr e IKs y la capacidad de respuesta a las catecolaminas conduce a una repolarización heterogénea de LV.
- Esta repolarización heterogénea es un componente clave del sustrato aritmogénico en perros pastores alemanes afligidos.
- Los hallazgos proporcionan información sobre las arritmias hereditarias y los mecanismos de muerte súbita.
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