التفاصيل البيبلوغرافية
| العنوان: |
Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity. |
| المؤلفون: |
Gonano, Luis Alberto, Sepúlveda, Marisa Noemí, Morell, Malena, Toteff, Tamara, Racioppi, María Florencia, Lascano, Elena Catalina, Negroni, Jorge Antonio, Fernández Ruocco, Maria Julieta, Medei, Emiliano, Neiman, Gabriel, Miriuka, Santiago Gabriel, Back, Thomas G., Chen, S. R. Wayne, Mattiazzi, Alicia Ramona, Vila Petroff, Martín Gerardo |
| سنة النشر: |
2018 |
| المجموعة: |
Universidad Nacional de La Plata (UNLP): SeDiCI (Servicio de Difusión de la Creación Intelectual) |
| مصطلحات موضوعية: |
Ciencias Médicas, Apoptosis, Arrhythmias, Carvedilol, Digitalis, VK-II-86 |
| الوصف: |
Background It has been shown that carvedilol and its non β-blocking analog, VK-II-86, inhibit spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). The aim of this study is to determine whether carvedilol and VK-II-86 suppress ouabain-induced arrhythmogenic Ca2+ waves and apoptosis in cardiac myocytes. Methods and Results: Rat cardiac myocytes were exposed to toxic doses of ouabain (50 µmol/L). Cell length (contraction) was monitored in electrically stimulated and non-stimulated conditions. Ouabain treatment increased contractility, frequency of spontaneous contractions and apoptosis compared to control cells. Carvedilol (1 µmol/L) or VK-II-86 (1 µmol/L) did not affect ouabain-induced inotropy, but significantly reduced the frequency of Ca2+ waves, spontaneous contractions and cell death evoked by ouabain treatment. This antiarrhythmic effect was not associated with a reduction in Ca2+ calmodulin-dependent protein kinase II (CaMKII) activity, phospholamban and ryanodine receptor phosphorylation or SR Ca2+ load. Similar results could be replicated in human cardiomyocytes derived from stem cells and in a mathematical model of human myocytes. Conclusions Carvedilol and VK-II-86 are effective to prevent ouabain-induced apoptosis and spontaneous contractions indicative of arrhythmogenic activity without affecting inotropy and demonstrated to be effective in human models, thus emerging as a therapeutic tool for the prevention of digitalis-induced arrhythmias and cardiac toxicity. ; Centro de Investigaciones Cardiovasculares ; Consejo Nacional de Investigaciones Científicas y Técnicas |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf; 41-51 |
| اللغة: |
English |
| Relation: |
http://sedici.unlp.edu.ar/handle/10915/124179 |
| الاتاحة: |
http://sedici.unlp.edu.ar/handle/10915/124179 |
| Rights: |
http://creativecommons.org/licenses/by-nc-sa/4.0/ ; Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
| رقم الانضمام: |
edsbas.A59CBB5C |
| قاعدة البيانات: |
BASE |