Inhomogeneous downregulation of INa underlies piceatannol proarrhythmic mechanism in regional ischemia-reperfusion

被引:8
作者
Chang, Po-Cheng [1 ,5 ]
Huang, Yu-Chang [1 ]
Lee, Hui-Ling [3 ,5 ]
Chang, Gwo-Jyh [2 ,5 ]
Chu, Yen [4 ,5 ]
Wen, Ming-Shien [1 ,5 ]
Chou, Chung-Chuan [1 ,5 ]
机构
[1] Chang Gung Mem Hosp, Dept Internal Med, Div Cardiol, Taipei, Taiwan
[2] Chang Gung Univ, Grad Inst Clin Med, Taoyuan, Taiwan
[3] Chang Gung Mem Hosp, Dept Anesthesia, Taipei, Taiwan
[4] Chang Gung Mem Hosp, Div Thorac Surg, Linkou, Taiwan
[5] Chang Gung Univ, Coll Med, Taoyuan, Taiwan
来源
PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY | 2018年 / 41卷 / 09期
关键词
heart failure; ischemia-reperfusion; piceatannol; sodium channel; ventricular arrhythmia; SODIUM-CHANNEL NA(V)1.5; ARRHYTHMIAS; EXPRESSION; MORTALITY;
D O I
10.1111/pace.13424
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundPiceatannol, a grape-derived polyphenol, has been linked to proarrhythmic properties by aggravating inhomogeneous conduction delay in the ischemia-reperfusion (IR) zone to enhance arrhythmogenic alternans in heart failure (HF) rabbits. The underlying molecular mechanisms of piceatannol-induced conduction disturbance were unclear in this model. MethodsHF was induced by 4 weeks' rapid ventricular pacing. IR injury was induced in vivo using a protocol of left coronary artery ligation and release. Left ventricular cardiomyocytes were isolated enzymatically for whole-cell patch-clamp studies. Piceatannol (10 M) was administrated to test its inhibitory effect on sodium current (I-Na). Immunoblots studies and immunoenzymological staining were conducted in tissues sampled from the IR and remote zones. ResultsPeak I-Na density was less in failing cardiomyocytes than control cardiomyocytes. IR injury further reduces peak I-Na density in both groups. Piceatannol showed a greater I-Na inhibitory effect in HF than control cardiomyocytes. Western blots showed reduced Na-V 1.5 protein expression in the HF group compared to the control group but no significant difference between remote and IR zones. Immunostaining showed that IR led to cytosolic redistribution of Na-V 1.5, especially in failing hearts. ConclusionsDownregulation of NaV 1.5 protein expression and reduced peak I-Na density are found in the failing hearts. Piceatannol exerts a greater inhibitory effect on peak I-Na in the failing cardiomyocytes than in the controls. IR injury further decreases peak I-Na density, which is more prominent in the failing hearts than in the control hearts.
引用
收藏
页码:1116 / 1122
页数:7
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