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La testosterona disminuye los efectos proarrítmicos del dofetilida en conejas hembras normales

Thai V Pham¹, Eugene A Sosunov, Evgeny P Anyukhovsky

¹Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Fla, USA.

|October 16, 2002

Resumen

La 5alfa-dihidrotestosterona (DHT) protege a las conejas femeninas de las drogas que prolongan la repolarización. Los niveles elevados de DHT reducen los efectos del fármaco y las despolarizaciones posteriores, lo que sugiere una protección androgénica contra las arritmias.

Área de la Ciencia:

Farmacología Cardiovascular Farmacología Cardiovascular
Endocrinología Endocrinología.
Electrofisiología Cardíaca Electrofisiología cardíaca.

Sus antecedentes:

La testosterona y su metabolito 5alfa-dihidrotestosterona (DHT) pueden ofrecer protección contra las drogas que prolongan la repolarización en los hombres.
Este estudio investigó si la DHT protege a las conejas hembras normales de la prolongación excesiva de la repolarización inducida por el fármaco.

Objetivo del estudio:

Para probar la hipótesis de que la 5alfa-dihidrotestosterona (DHT) protege a las mujeres normales contra la prolongación excesiva de la repolarización inducida por el fármaco.
Para determinar si la DHT influye en los efectos electrofisiológicos del dofetilido en conejas hembras.

Principales métodos:

Se utilizaron técnicas de microelectrodos para estudiar el endocardio ventricular de conejo aislado.
Los conejos hembras fueron tratados con DHT durante 4 semanas, y se midieron los niveles séricos de la hormona.
La duración del potencial de acción hasta el 90% de repolarización (APD90) y las despolarizaciones posteriores tempranas se evaluaron en respuesta a dofetilida.

Principales resultados:

Las hembras tratadas con DHT tenían una APD90 basal más corta en comparación con las hembras de control.
El aumento de la APD90 inducido por dofetilida fue significativamente menor en las mujeres tratadas con DHT.
La incidencia de despolarizaciones posteriores tempranas a una mayor concentración de dofetilida fue menor en las mujeres tratadas con DHT.

Conclusiones:

El aumento de los niveles de DHT reduce los efectos proarrítmicos de dofetilida en conejas hembras.
El tratamiento con DHT dio lugar a parámetros electrofisiológicos similares a los observados en los machos normales.
Estos hallazgos sugieren que la DHT y potencialmente otros andrógenos pueden proteger a las mujeres contra las arritmias inducidas por dofetilida.

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