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Efectos antiarrítmicos de los abridores de canales de potasio en las anomalías del ritmo relacionadas con la
L Carlsson1, C Abrahamsson, L Drews
1Department of Cardiovascular Pharmacology, Astra Hässle AB, Mölndal, Sweden.
Circulation
|April 1, 1992
Resumen
Los abridores de canales de potasio pinacidil y sus análogos P1075 y P1188 redujeron las taquiarritmias ventriculares polimórficas (PVT) inducidas por fármacos en conejos. Estos compuestos también abolieron las despolarizaciones posteriores tempranas y desencadenaron la actividad, lo que sugiere un potencial terapéutico para ciertas arritmias cardíacas.
Área de la Ciencia:
- Farmacología Cardiovascular Farmacología Cardiovascular
- Electrofisiología y electrofisiología.
- Modulación del canal iónico.
Sus antecedentes:
- Los medicamentos que retrasan la repolarización pueden inducir taquiarritmias ventriculares polimórficas (TVP), un tipo de torsión de punta.
- El potencial antiarrítmico de los abridores de canales de potasio contra los PVT requiere investigación.
Objetivo del estudio:
- Evaluar los efectos antiarrítmicos del pinacidil y sus análogos de piridilcianoguanidina (P1075, P1188) en los PVTs inducidos por clofilium.
- Investigar el impacto de estos compuestos en las despolarizaciones posteriores tempranas (EAD) y la actividad desencadenada en la electrofisiología cardíaca.
Principales métodos:
- Estudios in vivo en conejos usando clofilium y methoxamine para inducir PVTs, con el pretratamiento de pinacidil, P1075, o P1188.8.
- Registros electrofisiológicos in vitro de fibras de Purkinje de conejo y células musculares ventriculares para evaluar la duración del potencial de acción, los EAD y la actividad desencadenada.
- Bloqueo farmacológico con glibenclamida para explorar el papel de los canales de potasio sensibles al ATP.
Principales resultados:
- Pinacidil, P1075 y P1188 dependiendo de la dosis redujeron la incidencia de PVTs inducidos por clofilium.
- P1075 y P1188 demostraron efectos antiarrítmicos significativos, y las dosis altas impidieron por completo los PVT.
- In vitro, P1075 abolió los EAD inducidos por clofilium y desencadenó la actividad en las fibras de Purkinje, un efecto invertido por la glibenclamida.
- Diltiazem no atenuó la ocurrencia de PVT, a diferencia de las piridilcianoguanidinas.
Conclusiones:
- Los activadores de los canales de potasio sensibles al ATP son prometedores en la prevención y el tratamiento de los PVTs.
- Estos hallazgos sugieren un papel terapéutico para las piridilcianoguanidinas en el manejo de las arritmias asociadas con anomalías de repolarización.
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