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- Title
Inhomogeneous downregulation of I<sub>Na</sub> underlies piceatannol proarrhythmic mechanism in regional ischemia‐reperfusion.
- Authors
Chang, Po‐Cheng; Huang, Yu‐Chang; Lee, Hui‐Ling; Chang, Gwo‐Jyh; Chu, Yen; Wen, Ming‐Shien; Chou, Chung‐Chuan
- Abstract
Abstract: Background: Piceatannol, 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. Methods: HF 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 μM) was administrated to test its inhibitory effect on sodium current (INa). Immunoblots studies and immunoenzymological staining were conducted in tissues sampled from the IR and remote zones. Results: Peak INa density was less in failing cardiomyocytes than control cardiomyocytes. IR injury further reduces peak INa density in both groups. Piceatannol showed a greater INa inhibitory effect in HF than control cardiomyocytes. Western blots showed reduced NaV 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 NaV 1.5, especially in failing hearts. Conclusions: Downregulation of NaV 1.5 protein expression and reduced peak INa density are found in the failing hearts. Piceatannol exerts a greater inhibitory effect on peak INa in the failing cardiomyocytes than in the controls. IR injury further decreases peak INa density, which is more prominent in the failing hearts than in the control hearts.
- Subjects
CORONARY artery surgery; ANIMAL experimentation; GENE expression; HEART beat; HEART cells; HEART failure; IMMUNOBLOTTING; LIGATURE (Surgery); MEMBRANE proteins; MYOCARDIAL reperfusion complications; MYOCARDIUM; POLYPHENOLS; RABBITS; SODIUM; STAINS &; staining (Microscopy); WESTERN immunoblotting; PROARRHYTHMIA; IN vivo studies
- Publication
Pacing & Clinical Electrophysiology, 2018, Vol 41, Issue 9, p1116
- ISSN
0147-8389
- Publication type
Article
- DOI
10.1111/pace.13424