晚期电流有助于IKr抑制对心室再极化反向速度依赖的反向效应
1Department of Biology, Gilead Sciences, 1651 Page Mill Road, Palo Alto, CA 94304, USA. lin971@yahoo.com
抑制晚期电流 (晚期I(Na)) 缓解了I(Kr) 阻断剂的前节律逆速依赖性. 这一发现表明,晚期I(Na) 导致与胸肌相关的心室节律失常.
科学领域:
- 心脏病学 心脏病学
- 电子生理学 电子生理学
- 药理学 药理学是指药理学的学科.
背景情况:
- 阻断I(Kr) 药物的逆速率依赖 (RRD) 增加了动作潜力持续时间 (APD) 和反极化 (BVR) 的节拍变化,导致前节律失常.
- 在这种现象中,内源性晚期电流 (晚期I(Na)) 的作用尚未完全理解.
研究的目的:
- 确定抑制内源性晚期I(Na) 是否可以减轻RRD和I(Kr) 抑制的前节律效应.
- 调查晚期I ((Na) 对与胸相关的心室节律失常的贡献.
主要方法:
- 单相APD (MAPD) 和BVR测量在不同周期长度的雌性子心脏中.
- 心脏被用I(Kr) 阻断剂 (E-4031,d-sotalol) 治疗,并使用或不使用晚期I(Na) 抑制剂 (四毒素,拉诺拉).
- 还分析了心肌细胞和计算模型中的晚期I(Na).
主要成果:
- 克阻塞剂增加了MAPD (90%) 和BVR,在较慢的节奏速度下效果更大.
- 晚期I(Na) 抑制显著减弱了MAPD的RRD,减少了BVR,并取消了torsade de pointes.
- 晚期I(Na) 在较慢的速度时更大,在更快的速度下降;计算模型证实了RRD减弱与晚期I(Na) 抑制.
结论:
- 内生晚期I (Na) 促使I (Kr) 抑制剂诱导的APD和BVR的RRD增加.
- 抑制晚期I(Na) 减轻了心律失常效应,可能是与胸肌相关的腹腔失常症的治疗标.
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