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Efectos a corto y largo plazo de la amiodarona en los dos componentes del rectificador con retardo cardíaco K (((+)
K Kamiya1, A Nishiyama, K Yasui
1Department of Circulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. kamiya@riem.nagoya-u.ac.jp
Circulation
|March 10, 2001
Resumen
La amiodarona afecta los canales iónicos cardíacos de manera diferente según la duración del tratamiento. El uso a corto plazo inhibe I(Kr), mientras que el uso a largo plazo reduce I(Ks), lo que afecta el tratamiento de la taquiarritmia.
Área de la Ciencia:
- Cardiología Cardiología.
- Farmacología Farmacología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La amiodarona es crucial para el tratamiento de taquiarritmias potencialmente mortales en pacientes con enfermedad cardíaca estructural.
- Sus efectos complejos en los canales iónicos cardíacos pueden variar con la administración a corto plazo frente a la administración a largo plazo.
Objetivo del estudio:
- Investigar los efectos diferenciales de la amiodarona en los dos componentes de la corriente de potasio del rectificador retrasado (I(K)) I(Ks) y I(Kr) después de la administración a corto y largo plazo.
- Para comparar los efectos de la amiodarona en los canales cardíacos de conejos nativos y los canales humanos clonados.
Principales métodos:
- Técnica de pinza de tensión de célula entera en miocitos ventriculares de conejo para medir I(K), I(Kr) e I(Ks).
- Se utilizaron bloqueadores específicos (cromanol 293B para I(Ks), E-4031 para I(Kr)).
- Efectos evaluados en ovocitos de Xenopus que expresan los canales clonados HERG (I(Kr)) y KvLQT1/minK (I(Ks)).
- Se administró amiodarona oral a conejos durante 4 semanas para estudiar los efectos a largo plazo.
Principales resultados:
- La amiodarona a corto plazo inhibió el I(Kr) (IC50=2.8 μmol/L) con un efecto mínimo en el I(Ks) en los miocitos de conejo.
- En los ovocitos, la amiodarona inhibió la corriente de HERG (I(Kr)) (IC50=38 μmol/L) pero no la corriente de KvLQT1/minK (I(Ks)).
- El tratamiento a largo plazo con amiodarona (4 semanas) redujo el I ((K) total en un 55% y alteró la relación I ((Kr) / I ((Ks).
- No se observaron cambios significativos en los niveles de ARNm de ERG, KVLQT1 o minK después del tratamiento a largo plazo con amiodarona.
Conclusiones:
- La amiodarona exhibe efectos distintos en I(Kr) e I(Ks) en función de la duración de la administración.
- La amiodarona a corto plazo principalmente se dirige e inhibe a I ((Kr).
- La administración a largo plazo de amiodarona conduce a una reducción de I(Ks).
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