西尔德纳菲尔 (Viagra) 通过阻断延迟整流器电流的快速组成部分来延长心脏再极化
1Institut de Cardiologie de Québec, Hôpital Laval, et Facultés de Médecine, Université Laval, Sainte-Foy, Québec.
Circulation
|July 19, 2000
概括
西尔德纳菲尔延长心脏再极化并阻断电流,类似于抗心律不良药. 这可能解释易感患者的突然心脏死亡,特别是药物代谢受损的患者.
科学领域:
- 心血管药理学心血管药理学
- 心脏电生理学 心脏电生理学
背景情况:
- 在服用西尔代纳菲尔的缺血性心脏事件患者中报告的意外死亡.
- 假设:由于未经怀疑的电生理学效应,西尔德纳菲尔可能会导致前节律失常.
研究的目的:
- 调查西尔德纳菲尔对心脏复极化的电生理效应.
- 确定西尔德纳菲尔是否影响与心脏动作潜力相关的离子通道.
主要方法:
- 对隔离的几内亚猪心脏进行研究,以评估心脏再极化.
- 使用HERG转移的HEK293和CHO细胞进行实验,以评估对电流 (I(Kr)) 的影响.
主要成果:
- 西尔德纳菲尔以逆向使用依赖的方式延长了心脏再极化.
- 通过西尔代纳菲尔证明了延迟整流器电流 (I(Kr)) 的快速组件的度依赖性阻断.
- 在与药物排泄受损或过量剂量相关的度下观察到的影响.
结论:
- 西尔德纳菲尔表现出与III类抗失常药物相比的直接心脏电生理效应.
- 这些效应提供了一个潜在的机制,用于突然的心脏死亡在西尔德纳菲尔使用者.
- 在/肝功能不全,药物相互作用或过量服用的情况下强调了临床相关性.
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