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动作潜力的不稳定性和三角化预测严重的前节律失常,但动作潜力的持续时间延长是抗节律失常的
L M Hondeghem1, L Carlsson, G Duker
1Department of Pharmacology, Leuven, Belgium. luchondeghem@yahoo.com
Circulation
|April 18, 2001
概括
动作潜能持续时间 (APD) 延长可以是抗不律性或前不律性. APD的不稳定性和三角化决定了延长是否安全或诱导危险的心律失常,如torsade de pointes.
科学领域:
- 心脏电生理学心脏电生理学
- 药理学 药理学是指药理学的学科.
- 心血管研究的心血管研究.
背景情况:
- 动作潜能持续时间 (APD) 延长是一种已知的抗心律失常机制 (2I类).
- 矛盾的是,APD延长也可以诱导心律不整,特别是torsade de pointes.
- 了解这些相反作用的决定因素对于药物开发和患者安全至关重要.
研究的目的:
- 研究702种化学物质对心脏的电生理学影响.
- 确定确定APD延长是否是抗不节律或前不节律的关键因素.
- 为了将体外发现与体内节律不良潜力相关联.
主要方法:
- 利用子兰登多夫透气心脏模型来评估702种化学物质.
- 测量了APD的时间不稳定性,三角化,反向使用依赖性和宫外节拍诱导.
- 评估了前节律失常的结果,包括多态和单态心室动脉冲动,以及torsade de pointes.
主要成果:
- 时间不稳定,三角化和反向使用依赖被确定为前节律失常的关键决定因素.
- 延长APD (>50毫秒) 仅在不稳定和三角化存在时引起前节律失常.
- 在缺乏不稳定性和三角化的情况下,APD延长显示出显著的抗心律失常效应.
- 与不稳定和三角形相结合的APD缩短显然是前节律的.
- 在体外的不稳定性和三角测量强烈预测了体外的前节律失常 (torsade de pointes).
结论:
- 没有不稳定性或三角形的APD延长是抗失律的.
- APD的不稳定性和三角化是前节律失常的关键预测因素,取代了APD延长的影响.
- 这些发现对对心脏药物的安全性评估有重大影响.
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