Mechanisms of negative inotropic effects of class Ic antiarrhythmic agents: comparative study of the effects of flecainide and pilsicainide on intracellular calcium handling in dog ventricular myocardium.
Mechanisms of negative inotropic effects of class Ic antiarrhythmic agents: comparative study of the effects of flecainide and pilsicainide on intracellular calcium handling in dog ventricular myocardium.
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Ic类抗心律失常药的负性肌力作用机制：氟卡尼和匹西卡尼对狗心室肌细胞内钙处理影响的比较研究。
DOI：
10.1097/00005344-199601000-00008
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发表时间：
1996
影响因子：
3
通讯作者：
S. Sasayama
中科院分区：
文献类型：
--
作者：
Y. Kihara;M. Inoko;N. Hatakeyama;Y. Momose;S. Sasayama
我们研究了负责负性肌力作用的两个Ic类药物氟卡尼和pilsicainide的亚细胞机制。在离体犬心室肌小梁上同时记录了水母发光蛋白（Ca 2 +i）和等长张力。在同一心室的分离的心肌细胞中，记录慢内向电流（伊卡）。氟卡尼和匹西卡尼均依赖性地降低峰值Ca ~（2+）i、峰值张力和峰值伊卡浓度。氟卡胺的各项效应均较吡西卡尼显著，但Ca ~（2+）i和伊卡在张力变化上相互重叠，张力-Ca ~（2+）i-ICa关系曲线相同。我们的结论是，这些Ic类药物的负性肌力作用的差异主要与它们对L-型钙通道的影响以及随后在每个心动周期期间从肌浆网（SR）释放的钙量的减少有关。因此，其负性肌力作用可能与其抗心律失常作用的基本机制无直接关系。
We studied the subcellular mechanisms responsible for the negative inotropic effects of the two Ic drugs flecainide and pilsicainide. Aequorin luminescence (Ca2+i) and isometric tension were recorded simultaneously in isolated trabeculae from the dog ventricle. In isolated myocytes from the same ventricle, the slow inward current (ICa) was recorded. Both flecainide and pilsicainide decreased peak Ca2+i, peak tension, and peak ICa concentration dependently. Each effect with flecainide was more marked than that with pilsicainide; however, Ca2+i and ICa paralleled each other in changes in tension, and the tension-Ca2+i-ICa relationship showed the same curve for each drug. We conclude that the difference in negative inotropic effects of these class Ic drugs are primarily related to their effects on L-type Ca2+ channels and the subsequent decreases in the amount of Ca2+ released from the sarcoplasmic reticulum (SR) during each cardiac cycle. Therefore, their negative inotropic effects may not be directly correlated with the essential mechanisms responsible for their antiarrhythmic action.
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DOI：
10.1016/0002-9149(84)90513-7
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期刊：
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影响因子：
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DOI：
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发表时间：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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