Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/34547
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 18056/20254 (89%)
Visitors : 502675      Online Users : 589
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/34547


    Title: Ziprasidone Induces Rabbit Atrium Arrhythmogenesis via Modification of Oxidative Stress and Sodium/Calcium Homeostasis
    Authors: Tai, Buh-Yuan
    Lu, Ming-Kun
    Yang, Hsiang-Yu
    Tsai, Chien-Sung
    Lin, Chih-Yuan
    Contributors: Department of Pharmacy, Chia Nan University of Pharmacy & Science
    National Defense Medical Center
    Tri-Service General Hospital
    Keywords: sarcoplasmic-reticulum ca2+
    late sodium current
    protein-kinase-ii
    ventricular myocytes
    leak
    camkii
    risk
    fibrillation
    inhibition
    sudden
    Date: 2022
    Issue Date: 2023-12-11 13:57:14 (UTC+8)
    Publisher: MDPI
    Abstract: Background: Atypical antipsychotics increase the risk of atrial arrhythmias and sudden cardiac death. This study investigated whether ziprasidone, a second-generation antipsychotic, affected intracellular Ca2+ and Na+ regulation and oxidative stress, providing proarrhythmogenic substrates in atriums. Methods: Electromechanical analyses of rabbit atrial tissues were conducted. Intracellular Ca2+ monitoring using Fluo-3, the patch-clamp method for ionic current recordings, and a fluorescence study for the detection of reactive oxygen species and intracellular Na+ levels were conducted in enzymatically dissociated atrial myocytes. Results: Ziprasidone-treated atriums showed sustained triggered activities after rapid pacing, which were inhibited by KN-93 and ranolazine. A reduced peak L-type Ca2+ channel current and enhanced late Na+ current were observed in ziprasidone-treated atrial myocytes, together with an increased cytosolic Na+ level. KN-93 suppressed the enhanced late Na+ current in ziprasidone-treated atrial myocytes. Atrial myocytes treated with ziprasidone showed reduced Ca2+ transient amplitudes and sarcoplasmic reticulum (SR) Ca2+ stores, and increased SR Ca2+ leakage. Cytosolic and mitochondrial reactive oxygen species production was increased in atrial myocytes treated with ziprasidone. TNF-alpha and NLRP3 were upregulated in ziprasidone-treated myocytes, and the level of phosphorylated calcium/calmodulin-dependent protein kinase II protein was increased. Conclusions: Our results suggest that ziprasidone increases the occurrence of atrial triggered activity and causes intracellular Ca2+ and Na+ dysregulation, which may result from enhanced oxidative stress and activation of the TNF-alpha/NLRP3 inflammasome pathway in ziprasidone-treated myocytes.
    Relation: BIOMEDICINES, v.10, n.5, pp.976
    Appears in Collections:[Dept. of Pharmacy] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    biomedicines10050976.pdf2932KbAdobe PDF24View/Open
    index.html0KbHTML104View/Open


    All items in CNU IR are protected by copyright, with all rights reserved.

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback